Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer / A regulação positiva de GINS1 destacou um bom potencial diagnóstico e prognóstico de sobrevivência em três subtipos diferentes de câncer humano

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Effects of tumor derived exosomes on T cells markers expression / Efeitos de exossomos derivados de tumor na expressão de marcadores de células T

Exosomes are 30-120nm bio particles transferred from donor to recipient cells leading to modification in their regulatory mechanisms depending upon the coded message in the form of loaded biomolecule. Cancer cells derived exosomes the true representatives of the parent cells have been found to modify the tumor surrounding/distinct regions and participate in metastasis, angiogenesis and immune suppression. Tis study was aimed to study the effects of tumor mice derived exosomes on the normal mice spleen isolated T cells by using co-culture experiments and flow cytometer analysis. We mainly focused on some of the T cells population and cytokines including IFN-γ, FOXP3+ regulatory T (Treg) cells and KI67 (proliferation marker). Overall results indicated random changes in different set of experiments, where the cancer derived exosomes reduced the IFN-γ expression in both CD4 and CD8 T cells, similarly the Treg cells were also found decreased in the presence of cancer exosomes. No significant changes were observed on the Ki67 marker expression. Such studies are helpful in understanding the role of cancer exosomes in immune cells suppression in tumor microenvironment. Cancer exosomes will need to be validated in vivo and in vitro on a molecular scale in detail for clinical applications.

Os exossomos são biopartículas de 30-120 nm transferidas de células doadoras para células receptoras, levando à modificação em seus mecanismos reguladores, dependendo da mensagem codificada na forma de biomolécula carregada. Verificou-se que exossomos derivados de células cancerosas ­ os verdadeiros representantes das células-mãe ­ modificam as regiões circundantes / distintas do tumor e participam da metástase, angiogênese e imunossupressão. Este estudo teve como objetivo estudar os efeitos de exossomos derivados de camundongos com tumor nas células T isoladas de baço de camundongos normais, usando experimentos de cocultura e análise de citômetro de fluxo. Concentrou-se, principalmente, em algumas populações de células T e citocinas, incluindo IFN-γ, células T reguladoras FOXP3 + (Treg) e KI67 (marcador de proliferação). Os resultados gerais indicaram mudanças aleatórias em diferentes conjuntos de experimentos, em que os exossomos derivados de câncer reduziram a expressão de IFN-γ em células T CD4 e CD8, da mesma forma que as células Treg também foram encontradas diminuídas na presença de exossomos de câncer. Nenhuma mudança significativa foi observada na expressão do marcador Ki67. Esses dados são úteis para a compreensão do papel dos exossomos do câncer na supressão de células do sistema imunológico no microambiente tumoral. Exossomos de câncer precisarão ser validados in vivo e in vitro em escala molecular com detalhes para aplicações clínicas.

Murciélagos como vectores de enfermedades virales e impacto en la salud humana

Introducción: Los murciélagos se destacan por ser los únicos mamíferos voladores, con alrededor de 1 400 especies que cumplen un rol fundamental como controladores de plagas y polinizadores de plantas nocturnas. Sin embargo, su influencia sobre la salud humana se ha evidenciado cada vez más, en particular después del surgimiento de brotes epidémicos de enfermedades virales asociadas a estos mamíferos. Objetivo: Analizar la influencia de los murciélagos en la salud humana, centrándose en su papel como portadores de enfermedades virales y su potencial como reservorios y vectores de enfermedades. Métodos: Se realizó una revisión bibliográfica de la literatura utilizando descriptores MeSH y términos como: Animals, Wild Chiroptera, Virus Diseases, Zoonoses, Disease Vectors, Disease Reservoirs, Public Health, bats, Communicable Disease Control, Disease Outbreaks, Prevention and Control. Se revisaron 1 442 artículos en bases de datos y documentos oficiales, se seleccionaron las fuentes relevantes con Mendeley Desktop 1.19.4. y se obtuvieron al final 47 artículos. Resultados: Existen varias especies de murciélagos que pueden afectar la salud del ser humano y que albergan en especial virus de las familias Filoviridae, Coronaviridae y Paramixoviridae. Los murciélagos se consideran incubadoras óptimas para la propagación de virus debido a su sistema inmune único que lo hace resistente a estos agentes infecciosos. Conclusiones: La vigilancia y monitoreo de los murciélagos, junto con acciones de educación pública y una gestión adecuada de sus hábitats, son fundamentales para la detección temprana y prevención de la transmisión de nuevos virus de estos mamíferos a los humanos.

Introduction: Bats are the only flight mammals, with around 1,400 species playing critical roles as pest controllers and nocturnal plant pollinators. However, its impact on human health has become increasingly evident, especially after the appearance of epidemic outbreaks of viral diseases related to these mammals. Objetive: To analyze the influence of bats on human health, focusing on their role as carriers of viral diseases and their potential as reservoirs and vectors of diseases. Methods: A literature bibliographical review was conducted using MeSH descriptors and keywords such as: Animals, Wild Chiroptera, Virus Diseases, Zoonosis, Disease Vectors, Disease Reservoirs, Public Health, bats, Communicable Disease Control, Disease Outbreaks, Prevention and Control. 1442 articles in databases and official documents were reviewed, selecting the relevant sources with Mendeley Desktop 1.19.4., obtaining 47 articles at the end. Results: There are several species of bats that can affect human health and that mainly harbor viruses from the Filoviridae families, Coronaviridae and Paramyxoviridae. Bats are considered optimal incubators for the spread of the virus due to their unique immune system that makes them particularly resistant to these infectious agents. Conclusions: Surveillance and monitoring of bats, together with public education actions and proper management of their habitats, are essential for early detection and prevention of transmission of new viruses from these mammals to humans.

Viable Leishmania parasites in the absence of an in vitro IFN-γ response in asymptomatic carriers

ABSTRACT Asymptomatic infection (the absence or inapparent signs and symptoms) has been observed in many endemic areas of leishmaniasis, however, little is known about the parasitological and immunological factors associated with this type of infection. This study aimed to identify the in vitro expression of IFN-γ in asymptomatic carriers of viable Leishmania parasites. Asymptomatic infection was identified using the Montenegro skin test in an at-risk population from Yucatan, Mexico. Parasite viability was evinced in the blood by 7SL RNA transcripts amplification. The expression of mRNA IFN-γ was analyzed in peripheral blood mononuclear cells stimulated with soluble Leishmania antigen, using RT-qPCR. Parasite viability was observed in 33.3 % (5/15) of asymptomatic subjects. No differences were found in the expression of IFN-γ between asymptomatic and healthy subjects, and no correlation was found between the presence of viable parasites and the expression of IFN-γ. This study demonstrates the persistence of Leishmania parasites in the absence of an in vitro IFN-γ response in asymptomatic carriers from Mexico.

Corneal transplantation and concomitant SARS-CoV-2 infection: a case report / Transplante de córnea e infecção concomitante por SARS-CoV-2: relato de caso

ABSTRACT This report was aimed at presenting a case of neurotrophic keratitis and concomitant SARS-CoV-2 infection in a patient who has recently undergone a corneal DALK transplant. One month after corneal transplantation with adequate corneal epithelialization, the patient presented neurotrophic keratitis with a torpid course of the corneal transplant coinciding with a SARS-CoV-2 infection, with an excessive host immune response. In addition, the patient presented a re-positivization of nasopharyngeal polymerase chain reaction of SARS-CoV-2 with past disease after starting treatment with autologous serum eye drops. The implications at the ophthalmological level of SARS-CoV-2 infection may be clarified as the time the illness progresses and we learn more about how it acts. In this case, the disparity of signs and symptoms, the antecedent of corneal surgery, and the possibility of a herpetic infection as a cause of the primary leukoma suggested neurotrophic keratitis. Nonetheless, the involvement of systemic SARS-CoV-2 infection in the process, triggering an excessive host immune response at the corneal level with an increase in inflammatory cytokines must be taken into account. No relationship was found between treatment with autologous serum and re-positivization of nasopharyngeal polymerase chain reaction, presenting the patient a favorable response to treatment.

RESUMO O objetivo deste relato foi apresentar um caso de ceratite neurotrófica e infecção concomitante por SARS-CoV-2 em paciente submetido recentemente a transplante de córnea DALK. Um mês após o transplante de córnea com adequada epitelização da córnea, o paciente apresentou ceratite neurotrófica com curso tórpido do transplante de córnea, coincidindo com infecção por SARS-CoV-2, com resposta imune excessiva do hospedeiro. Além disso, o paciente apresentou repositivização da reação em cadeia da polimerase nasofaríngeo de SARS-CoV-2, com doença pregressa após iniciar tratamento com colírio de soro autólogo. As implicações a nível oftalmológico da infecção por SARS-CoV-2, podem ser esclarecidas à medida que a doença progride e aprendemos mais sobre sua forma de atuação. Neste caso, a disparidade de sinais e sintomas, o antecedente de cirurgia de córnea e a possibilidade de infecção herpética como causa do leucoma primário sugeriram ceratite neurotrófica. No entanto, deve-se levar em consideração o envolvimento da infecção sistêmica por SARS-CoV-2 no processo, desencadeando uma resposta imune excessiva do hospedeiro no nível da córnea, com aumento de citocinas inflamatórias. Não foi encontrada relação entre o tratamento com soro autólogo e a repositivização da reação em cadeia da polimerase nasofaríngea, apresentando ao paciente uma resposta favorável ao tratamento.

Vitreous metastasis from cutaneous melanoma: diagnosis and management / Metástase vítrea de melanoma cutâneo: diagnóstico e tratamento

ABSTRACT Purpose: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma. Methods: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported. Results: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells. Conclusions: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated.

RESUMO Objetivo: Descrever os achados clínicos, tratamentos, e desfechos em uma série de pacientes com me tástases vítreas de melanoma cutâneo. Métodos: Série retrospectiva de casos de único centro com intervenção. Pacientes incluídos tiveram seu diagnóstico de MVMC confirmado por biópsia entre 1997 e 2020. Vitrectomia via pars plana com 23 ou 25 gauge foram realizadas para obter espécimens. Esclerotomias foram tratadas com crioterapia em duplo ou triplo congelamento. Injeção intravítrea perioperatória de melfalano (32 ug/0,075 mL) foi administrada quando necessário. Foram relatados acuidade visual, pressão intraocular, resposta terapêutica sistêmica e ocular. Resultados: Cinco olhos de 5 pacientes com metástases vítreas de melanoma cutâneo unilateral foram identificados. Idade média de diagnóstico foi 84 anos (variando de 37-88). Seguimento médio após diagnóstico oftalmológico foi 28 (8,5-36) meses; 1 paciente não teve acompanhamento. Acuidade visual inicial variou de 20/30 a movimentos de mão. Achados clínicos iniciais incluíram infiltração de células pigmentadas e não-pigmentadas no vítreo (5/5), segmento anterior (4/5), e retina (3/5). Quatro pacientes tiveram glaucoma secundário. Tratamento sistêmico incluiu imunoterapia com inibidores da via de sinalização (3 - todos com resposta parcial/completa), quimioterapia sistêmica (2), ressecção cirúrgica (3), e irradiação (2). Intervalo médio entre diagnóstico primário e metástases vítreas foi 2 (2-15) anos. Um paciente teve doença sistêmica ativa simultânea as metástases vítreas. Acuidade visual final variou entre 20/40 e SPL. Tratamento oftalmológico incluiu vitrectomia nos 5 pacientes, melfalano intravítreo em 3 e metotrexato intravítreo em 1. Um paciente precisou de enucleação. A histopatologia revelou invasão celular extensa de melanoma. Conclusões: Metástases vítreas de melanoma cutâneo pode se manifestar como uma infiltração difusa de células pigmentadas e não-pigmentadas no vítreo e erroneamente diagnosticada como uveites. Vitrectomia diagnóstica e quimioterapia intravítrea periódica podem estar indicadas.

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Effects of tumor derived exosomes on T cells markers expression

Abstract Exosomes are 30-120nm bio particles transferred from donor to recipient cells leading to modification in their regulatory mechanisms depending upon the coded message in the form of loaded biomolecule. Cancer cells derived exosomes the true representatives of the parent cells have been found to modify the tumor surrounding/distinct regions and participate in metastasis, angiogenesis and immune suppression. Tis study was aimed to study the effects of tumor mice derived exosomes on the normal mice spleen isolated T cells by using co-culture experiments and flow cytometer analysis. We mainly focused on some of the T cells population and cytokines including IFN-, FOXP3+ regulatory T (Treg) cells and KI67 (proliferation marker). Overall results indicated random changes in different set of experiments, where the cancer derived exosomes reduced the IFN- expression in both CD4 and CD8 T cells, similarly the Treg cells were also found decreased in the presence of cancer exosomes. No significant changes were observed on the Ki67 marker expression. Such studies are helpful in understanding the role of cancer exosomes in immune cells suppression in tumor microenvironment. Cancer exosomes will need to be validated in vivo and in vitro on a molecular scale in detail for clinical applications.

Resumo Os exossomos são biopartículas de 30-120 nm transferidas de células doadoras para células receptoras, levando à modificação em seus mecanismos reguladores, dependendo da mensagem codificada na forma de biomolécula carregada. Verificou-se que exossomos derivados de células cancerosas os verdadeiros representantes das células-mãe modificam as regiões circundantes / distintas do tumor e participam da metástase, angiogênese e imunossupressão. Este estudo teve como objetivo estudar os efeitos de exossomos derivados de camundongos com tumor nas células T isoladas de baço de camundongos normais, usando experimentos de cocultura e análise de citômetro de fluxo. Concentrou-se, principalmente, em algumas populações de células T e citocinas, incluindo IFN-, células T reguladoras FOXP3 + (Treg) e KI67 (marcador de proliferação). Os resultados gerais indicaram mudanças aleatórias em diferentes conjuntos de experimentos, em que os exossomos derivados de câncer reduziram a expressão de IFN- em células T CD4 e CD8, da mesma forma que as células Treg também foram encontradas diminuídas na presença de exossomos de câncer. Nenhuma mudança significativa foi observada na expressão do marcador Ki67. Esses dados são úteis para a compreensão do papel dos exossomos do câncer na supressão de células do sistema imunológico no microambiente tumoral. Exossomos de câncer precisarão ser validados in vivo e in vitro em escala molecular com detalhes para aplicações clínicas.

Regulation of Immune Balance by Traditional Chinese Medicine in Treatment of Cough Variant Asthma： A Review / 中国实验方剂学杂志

Cough variant asthma （CVA） is a chronic respiratory disease with cough as its main symptom. The occurrence of CVA is closely related to non-specific airway inflammation， and its pathogenesis involves environmental， genetic， immune， and other factors. In recent years， the advantages of traditional Chinese medicine （TCM） in the treatment of CVA have attracted the attention of experts and scholars in China and abroad， especially its prominent role in regulating immune balance， relieving cough symptoms in CVA patients， and reducing recurrence. T Helper cells 1 （Th1）， T helper cells 2 （Th2）， T helper cells 17 （Th17）， and regulatory T cells （Treg） are derived from CD4+ T cells. Immune imbalance of Th1/Th2 and Th17/Treg is a new hotspot in the pathogenesis of CVA and a potential key target in the treatment of CVA by TCM. Th cell subsets are in dynamic balance under physiological conditions， maintaining respiratory immune homeostasis in which pro-inflammatory cytokines and anti-inflammatory cytokines are balanced. Immature helper T cells （Th0） can be differentiated into Th1， Th2， Th17， Treg， and other cell subsets due to cytokine types in the microenvironment in the stage of CVA maturation. The proliferation of Th2 cells leads to eosinophilic airway inflammation. Excessive differentiation of Th17 cells induces neutrophil airway inflammation. Th1/Th2 and Th17/Treg cells are mutually restricted in number and function， and the immune imbalance of Th1/Th2 and Th17/Treg is easy to aggravate the generation of inflammatory response. Restoring immune balance is particularly important for the airway anti-inflammatory therapy of CVA. In this paper， the imbalance of Th1/Th2 and Th17/Treg and the pathogenesis of CVA were systematically expounded. Meanwhile， the latest research on the regulation of immune imbalance by TCM compound， single TCM， and its effective ingredients in the treatment of CVA was reviewed. It provides ideas and references for revealing the scientific connotation of TCM regulating immune balance therapy of CVA， as well as the development of clinical treatment and basic research of CVA.

Síndrome inflamatorio de reconstitución inmunológica (SIRS) en la salud reproductiva / Immune reconstitution inflammatory syndrome (IRIS) in reproductive health

Resumen El embarazo es un proceso que genera grandes cambios inmunitarios en los cuales participan los linfocitos T con respuestas proinflamatorias (Th1/Th17) y antiinflamatorias (Th2/Treg), con la finalidad de mantener el óptimo estado y desarrollo fetal. En la infección por VIH estos ambientes inmunológicos son afectados directamente con el descenso de las células TCD4. El uso de antirretrovirales (ART) ha permitido que las mujeres que viven con VIH puedan disminuir de manera importante la posibilidad de infectar a sus productos con el virus. El embarazo, enfermedades autoinmunes y el uso de ART son factores conocidos para el desarrollo del síndrome inflamatorio de reconstitución inmunológica debido a la recuperación abrupta de la respuesta inmunitaria. En esta revisión describimos parte de estos cambios en el embarazo y puerperio sin patología añadida, además proponemos un posible comportamiento en los perfiles Th1/Th2 en mujeres que viven con VIH que reciben ART y cursan el primer año posparto.

Abstract Pregnancy is a process which generate great immunologic changes with participation of T lymphocytes with inflammatory (Th1/Th17) and anti-inflammatory response (Th2/Treg), with the purpose of maintain the optimum condition and fetal development. In HIV infection this immunological ambient are affected directly due the decrease of T CD4 cells. The use of antiretrovirals (ART) has allowed that women living with HIV can decrease the possibility to infect their newborns with the virus. The pregnancy, autoimmune diseases, and the use of ART are known factors for the progress of immune reconstitution inflammatory syndrome due to the abrupt recovery of immune response. In this review we describe some of these changes during the pregnancy and puerperium without any disease added, furthermore we propose a possible behavior of Th1/Th2 profile in women who live with HIV and receive ART during the first year of postpartum.

Anatomía Comparada del Bazo de la Rata Blanca (Rattus norvegicus albinus), Una Revisión de la Literatura / Comparative Anatomy of the Spleen of the White Rat, (Rattus norvegicus albinus) a Literature Review

El bazo es el órgano linfático intraperitoneal más grande del organismo, presentando dos funciones principales: defensiva, mediante respuesta inmunitaria y filtración sanguínea. El objetivo de la presente revisión, fue obtener información actualizada sobre la anatomía del bazo de la rata albina (Rattus norvegicus albinus) y comparativa con la anatomía del bazo humano, perro, gato y cerdo, al representar las principales especies de importancia en la medicina, medicina veterinaria y en las ciencias biomédicas. Se realizó una búsqueda de material bibliográfico actualizado en diferentes sitios web científicos. Es así como, se revisaron 71 fuentes bibliográficas, en su gran mayoría artículos científicos (31), libros de anatomía humana y veterinaria (17), artículos especializados (17) y tesis (6). En general existe consenso, sobre la descripción anatómica del bazo, el cual se sitúa en la región hipocondriaca izquierda del abdomen, entre el fondo del estómago y el diafragma, irrigado por la arteria y vena esplénica. Se evidenció que existen similitudes en aspectos macroscópicos, al comparar el bazo de la rata blanca, con el bazo de otras especies (funcionalidad, peso relativo, ubicación topográfica). En aspectos microscópicos, el bazo en humanos y otros mamíferos se compone de estroma, además de parénquima, constituido a su vez por pulpa blanca y roja. En particular, existen diferencias entre el bazo de rata, humano, gato, perro y cerdo, en formas, tamaños y aspectos microscópicos, relacionados con la microcirculación e inmunidad. Mientras que existen semejanzas en procesos patológicos y respuestas a tratamientos farmacológicos y clínicos. Por lo anteriormente expuesto, se concluye que la rata albina constituye un buen modelo biológico, específicamente en aspectos anatómicos microscópicos del bazo de tipo inmunológico. Mientras que el bazo de cerdo es mejor comparativamente, en estudios anatómicos macroscópicos de tipo quirúrgicos, resultando ambos extrapolables, especialmente a la medicina humana.

SUMMARY: The spleen is the largest intraperitoneal lymphatic organ of the body, presenting two main functions: defensive, through immune response and blood filtration. The objective of the present review was to obtain updated information on the anatomy of the spleen of the albino rat (Rattus norvegicus albinus) and to compare it with the anatomy of the human, dog, cat and pig spleen, representing the main species of importance in medicine, veterinary medicine and biomedical sciences. A search for updated bibliographic material was carried out in different scientific websites. Thus, 71 bibliographic sources were reviewed, mostly scientific articles (31), human and veterinary anatomy books (17), specialized articles (17) and theses (6). In general, there is consensus on the anatomical description of the spleen, which is located in the left hypochondriac region of the abdomen between the fundus of the stomach and the diaphragm, irrigated by the splenic artery and vein. It was evidenced that there are similarities in macroscopic aspects when comparing the spleen of the white rat with the spleen of other species (functionality, relative weight, topographic location). In microscopic aspects, the spleen in humans and other mammals is composed of stroma, in addition to parenchyma, constituted in turn by white and red pulp. In particular, there are differences between rat, human, cat, dog and pig spleens in shapes, sizes and microscopic aspects related to microcirculation and immunity. While there are similarities in pathological processes and responses to pharmacological and clinical treatments. For the above mentioned, it is concluded that the albino rat constitutes a good biological model, specifically in microscopic anatomical aspects of the spleen of immunological type. While the pig spleen is comparatively better in macroscopic anatomical studies of surgical type, both are extrapolable especially to human medicine.

Comprehensive Analysis of CLCA1 Expression, Immune Infiltration and Immune Checkpoints in Colon Adenocarcinoma / Análisis Completo de la Expresión de CLCA1, Infiltración Inmune y Puntos de Control Inmunológico en Colonadenocarcinoma

SUMMARY: Colon adenocarcinoma (COAD) is a prevalent disease worldwide, known for its high mortality and morbidity rates. Despite this, the extent of investigation concerning the correlation between COAD's CLCA1 expression and immune cell infiltration remains insufficient. This study seeks to examine the expression and prognosis of CLCA1 in COAD, along with its relationship to the tumor immune microenvironment. These findings will offer valuable insights for clinical practitioners and contribute to the existing knowledge in the field. In order to evaluate the prognostic significance of CLCA1 in individuals diagnosed with colorectal cancers, we conducted a comprehensive analysis using univariate and multivariate Cox regression models along with receiver operating characteristic curve (ROC) analysis. This study was performed on the patient data of COAD obtained from The Cancer Genome Atlas (TCGA) database. Nomograms were developed to anticipate CLCA1 prognostic influence. Furthermore, the CLCA1 association with tumor immune infiltration, immune checkpoints, immune checkpoint blockade (ICB) response, interaction network, and functional analysis of CLCA1-related genes was analyzed. We found that Colon adenocarcinoma tissues significantly had decreased CLCA1 expression compared to healthy tissues. Furthermore, the study revealed that the group with high expression of CLCA1 demonstrated a significantly higher overall survival rate (OS) as compared to the group with low expression. Multivariate and Univariate Cox regression analysis revealed the potential of CLCA1 as a standalone risk factor for COAD. These results were confirmed using nomograms and ROC curves. In addition, protein-protein interaction (PPI) network analysis and functional gene enrichment showed that CLCA1 may be associated with functional activities such as pancreatic secretion, estrogen signaling and cAMP signaling, as well as with specific immune cell infiltration. Therefor, as a new independent predictor and potential biomarker of COAD, CLCA1 plays a crucial role in the advancement of colon cancer.

El adenocarcinoma de colon (COAD) es una enfermedad prevalente a nivel mundial, conocida por sus altas tasas de mortalidad y morbilidad. Sin embargo, el alcance de la investigación sobre la correlación entre la expresión de CLCA1 de COAD y la infiltración de células inmunes sigue siendo insuficiente. Este estudio busca examinar la expresión y el pronóstico de CLCA1 en COAD, junto con su relación con el microambiente inmunológico del tumor. Estos hallazgos ofrecerán conocimientos valiosos para los profesionales clínicos y contribuirán al conocimiento existente en el campo. Para evaluar la importancia de pronóstico de CLCA1 en personas diagnosticadas con cáncer colorrectal, realizamos un análisis exhaustivo utilizando modelos de regresión de Cox univariados y multivariados junto con un análisis de la curva característica operativa del receptor (ROC). Este estudio se realizó con los datos de pacientes de COAD obtenidos de la base de datos The Cancer Genome Atlas (TCGA). Se desarrollaron nomogramas para anticipar la influencia pronóstica de CLCA1. Además, se analizó la asociación de CLCA1 con la infiltración inmunitaria tumoral, los puntos de control inmunitarios, la respuesta de bloqueo de los puntos de control inmunitarios (ICB), la red de interacción y el análisis funcional de genes relacionados con CLCA1. Descubrimos que los tejidos de adenocarcinoma de colon tenían una expresión significativamente menor de CLCA1 en comparación con los tejidos sanos. Además, el estudio reveló que el grupo con alta expresión de CLCA1 demostró una tasa de supervivencia general (SG) significativamente mayor en comparación con el grupo con baja expresión. El análisis de regresión de Cox multivariado y univariado reveló el potencial de CLCA1 como factor de riesgo independiente de COAD. Estos resultados se confirmaron mediante nomogramas y curvas ROC. Además, el análisis de la red de interacción proteína- proteína (PPI) y el enriquecimiento de genes funcionales mostraron que CLCA1 puede estar asociado con actividades funcionales como la secreción pancreática, la señalización de estrógenos y la señalización de AMPc, así como con la infiltración de células inmunes específicas. Por lo tanto, como nuevo predictor independiente y biomarcador potencial de COAD, CLCA1 desempeña un papel crucial en el avance del cáncer de colon.

To study the effect of 'Covishield' vaccination on pre-donation platelet counts of plateletpheresis donors

ABSTRACT Introduction: Approximately 55.52% of the Indian population had been fully vaccinated by Jan. 2022, since its first roll out on January 16, 2021. A few concerns were raised concerning the Covishield vaccination related to thrombotic thrombocytopenia. Apheresis-derived platelet concentrates are frequently required in a plethora of clinical situations and post-vaccination decrement of platelet counts might lead to increased deferral of the plateletpheresis donors. Objectives. The aim of the study was to discover the effect of the Covishield vaccination on deferral rates of plateletpheresis donors. Methods: Blood samples were collected from the potential platelet donors for the completion of the standard questionnaire for the complete blood count. The data collected were tabulated in the MS Excel spreadsheet and the biostatistical analysis was performed with the SPSS v23. A p-value of < 0.05 was taken as significant. We compared this data with age-and sex-matched controls. Results: The mean age of cases and controls was 29.69 ± 8.57 and 30.15 ± 7.11, respectively. There was a significant difference in platelet counts of cases (188496.35 ± 72065.66/cumm) and controls (269524.50 ± 53981.60/cumm). Furthermore, donors who received one dose had higher platelet counts of 248676.47 ± 80075.24/cumm than those who received both doses of vaccine (179970.83 ± 66773.73/cumm). The difference in deferral rates between the two groups was remarkable (34.7% vs. 0.9%, with the p-value < 0.001). Conclusion: Vaccination certainly increased the deferral rates of plateletpheresis donors due to low platelet counts. Average platelet counts were low in fully vaccinated individuals, however, the platelets returned to normal counts as the post-vaccination days progressed.

Respuesta inmune en pacientes con diagnóstico de lepra

Introducción: La lepra es una entidad de expresión florida con afectación frecuente en el tegumento cutáneo y los nervios periféricos, por la predisposición que presenta el Mycobacterium leprae a estas estructuras. Las reacciones leprosas pueden aparecer en el curso de la enfermedad. Estas interrumpen la evolución crónica usual y la estabilidad clínica de los pacientes que la padecen. Objetivo: Caracterizar los estados reaccionales de la lepra. Materiales y métodos: Se realizó un estudio descriptivo en el período de enero de 2019 a septiembre de 2022, en pacientes que acudieron a la Consulta Provincial de Lepra en el Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, de Matanzas. El universo estuvo constituido por 8 pacientes que presentaron estados reaccionales en la etapa mencionada. Se recogieron de las historias clínicas variables como: edad, sexo, clasificación de la lepra según Ridley-Jopling, tipo de estado reaccional, forma clínica y momento de aparición. Resultados: La mayor frecuencia estuvo entre el rango de 50 a 64 años, con un 50 %. El sexo masculino representa el 62,5 %. Se mostró prevalencia de la lepra lepromatosa en el 62,5 %. La reacción tipo II y las formas graves fueron las más frecuentes, con un 62,5 % y 75 % respectivamente. Existió predominio de las reacciones leprosas durante y después del tratamiento, sin diferencias entre estas, con un 37,5 %. Conclusiones: La reacción tipo II y las formas graves de presentación fueron las predominantes en pacientes masculinos, representados en el grupo etario de 50 a 64 años. La forma clínica preponderante en estos eventos fue la lepromatosa.

Introduction: Leprosy is a floridly expressed entity with frequent involvement of the cutaneous integument and peripheral nerves due to the predisposition of Mycobacterium leprae to these structures. Leprosy reactions may appear during the course of the disease. These interrupt the usual chronic course and the clinical stability of patients suffering from the disease. Objective: To characterize the reactional states of leprosy. Materials and methods: A descriptive study was carried out from January 2019 to September 2022 in patients who attended the Provincial Leprosy Clinic at the Clinical Surgical University Hospital Comandante Faustino Pérez Hernández, in Matanzas. The universe consisted of 8 patients who presented reactional states in the aforementioned stage. The variables, collected from the clinical records, were: age, sex; classification of leprosy according to Ridley-Jopling, type of reactional state, clinical form and time of onset. Results: The highest frequency was between 50 and 64 years, with 50%. The male sex represents 62.5%. Lepromatous leprosy prevalence was shown in 62.5%. The type II reaction and severe forms were the most frequent with 62.5% and 75% respectively. There was predominance of leprosy reactions during and after treatment without differences between them, with 37.5%. Conclusions: The type II reaction with severe forms of presentation was predominant in male patients represented in the age group of 50 to 64 years. The predominant clinical form in these events was the lepromatous one.

COVID-19 en las embarazadas. Riesgo de las complicaciones durante el embarazo y en el neonato / COVID-19 in pregnant women. Risk of complications during pregnancy and in the newborn

Sobre el tema COVID-19 se han publicado múltiples estudios que reflejan su elevada incidencia, transmisibilidad, morbilidad y mortalidad, con gran repercusión y severidad en los grupos poblacionales de riesgo. El embarazo no escapa a ello, y la inmunosupresión fisiológica que se presenta en esta condición, hace a la gestante y al neonato, ser más susceptibles a las enfermedades infecciosas. El objetivo de esta comunicación es profundizar en la fisiopatología y la repercusión de la enfermedad COVID-19 en las gestantes y el neonato, para mejorar el conocimiento relacionado con el tema, el cual repercutirá en un mejor manejo de estos pacientes. Para ello, se realizó una revisión de investigaciones publicadas en el período comprendido entre enero y diciembre de 2021, en las bases de datos: SciELO, SCOPUS, Medline, Dialnet, Cumed y Lilacs. De los 44 artículos obtenidos inicialmente, 33 cumplieron los criterios de inclusión.

Several studies on COVID-19 have been published reflecting its high incidence, transmissibility, morbidity and mortality, with great repercussions and severity in population groups at risk. Pregnancy does not escape from this, and the physiological immunosuppression that occurs in this condition makes the pregnant woman and the newborn more susceptible to infectious diseases. The objective of this communication is to deepen the pathophysiology and the repercussion of the COVID-19 disease in pregnant women and the newborn in order to improve knowledge related to the subject, which will have an impact on better management of these patients. For this, a review of research published between January and December 2021 was carried out in the databases such as SciELO, SCOPUS, Medline, Dialnet, Cumed and Lilacs. A number of 33 articles met the inclusion criteria from 44 initially obtained.

Vasculitis pauciinmune asociada a lupus eritematoso sistémico: a propósito de un caso

Introducción: la poliangeítis microscópica (PAM) hace parte del grupo de vasculitis asociadas a anticuerpos anticitoplasmáticos de neutrófilos (ANCA), cuya presencia de anticuerpos contra mieloperoxidasa (MPO) se observa en la mayoría de los casos (70-95 %), asimismo, el compromiso renal presagia mayores tasas de morbilidad y mortalidad, sin embargo, la coexistencia con lupus eritematoso sistémico (LES) es poco frecuente y con mayor énfasis en la variante de LES del adulto mayor o de inicio tardío. Objetivo: dar a conocer un caso poco común de dos enfermedades autoinmunes, lo cual ha sido reportado como síndrome de superposición y brindar información útil que permita ampliar los diagnósticos diferenciales. Presentación del caso: se presenta el caso de un paciente masculino de 76 años con historia de poliartralgias progresivas en deterioro del estado general, con debut en síndrome confusional agudo, caída de filtrado glomerular, microhematuria y proteinuria casi nefrótica. A la evaluación inicial se encontró anemia y trombocitopenia severa, en perfil inmune ANA 1/320 y complemento consumido, cumpliendo criterios para LES, ANCA reactivo específicamente MPO ANCA (1/320) y sospecha de glomerulonefritis con patrón rápidamente progresivo (GNRP). Dado el contexto clínico, se decidió comenzar con pulsos de metilprednisolona consecutivos, seguidos de prednisolona oral y, como terapia de mantenimiento, se instauró ciclofosfamida. Finalmente, con una biopsia renal se confirmó el diagnóstico de vasculitis sistémica pauciinmune con formación de crescencia celular. La evolución clínica del paciente fue satisfactoria, logrando la estabilización de órganos y la normalización de la función renal, hematopoyética y el estado neurológico. Discusión y conclusión: dado que la presentación clínica de LES es heterogénea, se ha reportado su asociación con vasculitis, las cuales comparten un compromiso común de órganos como articulaciones, piel y riñones. Los hallazgos paraclínicos, como por biopsia, fueron consistentes tanto con PAM como con LES, por lo tanto, se diagnosticó como un caso de superposición. Este caso demuestra el enigma del diagnóstico y la complejidad en el manejo de entidades poco frecuentes, de etiologías inmunológicas superpuestas que ponen en peligro la vida de quien la(s) padece, de no tener un diagnóstico oportuno y un tratamiento temprano.

Introduction: Microscopic polyangiitis (MPA) is part of the group of vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA), whose presence of antibodies against myeloperoxidase (MPO) is observed in most cases (70-95 %), likewise, the renal compromise portends higher rates of morbidity and mortality. However, coexistence with Systemic Lupus Erythematosus (SLE) is infrequent, and with greater emphasis on the older adult or late-onset variant of SLE (1). Purpose: Present a rare case of two autoimmune diseases, which has been reported as overlapping syndrome and provide useful information that allows expanding differential diagnoses. Case report: We present the case of a 76-year-old male patient with a history of progressive polyarthralgias in deteriorating general condition, with debut in acute confusional syndrome, drop in glomerular filtration rate, microhematuria and almost nephrotic proteinuria. At the initial evaluation anemia and severe thrombocytopenia were found, in the immune profile ANA 1/320, complement consumed; fulfilling criteria for SLE, ANCAs reactive specifically MPO ANCA (1/320) and suspected Rapidly Progressive Renal Insufficiency (PRRI). Given the clinical context, it was decided to start consecutive pulses of methylprednisolone followed by oral prednisolone, and cyclophosphamide was established as maintenance therapy. Finally, a renal biopsy confirmed the diagnosis of pauci-immune systemic vasculitis with cell crescent formation. These findings were consistent with both SLE and PAM, thus it was diagnosed as a case of overlap. The clinical evolution of the patient was satisfactory, achieving organ stabilization and normalization of renal function, hematopoietic function, and neurological status. Discussion and conclusion: RPGN associated with ANCA present non-nephrotic proteinuria, glomerular filtration rate drop. The most common is anti-glomerular basement membrane (AMBG) antibodies. Serological detection of antineutrophil cytoplasmic antibodies, PR3 and MPO should be available. Microscopic polyangiitis could be determined by renal biopsy, with the presence of cell growth, absence of immune deposits and MPO ANCA positivity. This case is a diagnostic enigma, and the complexity in the management of rare entities, of immunological etiology, superimposed that endanger the life of those who suffer from it, if they do not have a timely diagnosis and early treatment.

La función de las proteínas de choque térmico en las infecciones virales / The Role of Heat Shock Proteins in Viral Infections

Resumen Las proteínas de choque térmico se describieron como una respuesta intracelular al estrés calórico; sin embargo, al paso del tiempo, se observó que estas proteínas tienen múltiples funciones y que participan de manera relevante tanto en los procesos fisiológicos como patológicos. Las actividades que realizan las proteínas de choque térmico se relacionan con su localización, que puede ser intra o extracelular, al momento fisiológico y a las diferentes asociaciones estructurales, que pueden ser desde péptidos derivados de estas, hasta dímeros o multímeros. Con base en estas características funcionales, se les ha denominado proteínas multiempleo o "moonlighting proteins". En este artículo se describen algunas de las actividades de estas proteínas con relación al sistema inmunológico y las infecciones virales, en particular con los procesos inflamatorios.

Abstract Heat shock proteins (HSP) were first described as a cell response to heat stress. However, over time, it has become clear they have multiple functions inside and outside cells, and that they actively participate in different physiological and pathological processes. They perform functions related to their cellular location or physiological moment, which is why they have been called multi-use proteins or "moonlighting proteins". Furthermore, HSP activity is associated with different structural conformations, from peptides derived from them or as dimers or multimers, to mention a few. This article describes these functions and their relationship with the immune system, and their relationship with viral infection, particularly with inflammatory processes.

Diabetes mellitus tipo 1 de presentación súbita inducida por inhibidores del punto de control inmunitario en el tratamiento de cáncer avanzado. Serie de casos / Sudden onset type 1 diabetes mellitus induced by immune checkpoint inhibitors in the treatment of advanced cancer. Cases report

Tres pacientes con cáncer avanzado en tratamiento con inhibidores del punto de control inmunitario (inmune checkpoint inhibitors, ICIs), sin antecedentes de diabetes mellitus (DM), ingresaron al Servicio de Urgencias con poliuria, polidipsia y pérdida de peso, y diagnóstico de cetoacidosis diabética, sin evidencia clínica de infección. Fueron tratados con líquidos e infusión de insulina pasando luego a un régimen de insulina bolo basal que continuó después del alta. Las pruebas de detección de autoanticuerpos para DM resultaron negativas, y se les diagnosticó DM inducida por ICIs, pembrolizumab en dos de ellos y nivolumab en el otro. El propósito de esta serie de casos es demostrar el desarrollo de la DM1 en forma aguda en pacientes tratados con inhibidores de PD-1. Sobre la base de estos casos y la literatura revisada, se buscaron determinar las características clínicas, y sugerir estrategias para la identificación, control, tratamiento precoz y seguimiento de los pacientes tratados con ICIs a fin de minimizar el impacto de la disfunción autoinmune.

Three patients with advanced cancer, treated with inmune checkpoint inhibitors (ICIs), with no history of diabetes mellitus (DM), were admitted to the Emergency Department with polyuria, polydipsia, and weight loss and a diagnosis of diabetic ketoacidosis without clinical evidence of infection. They were treated with fluids and insulin infusion transitioning to a basal-bolus insulin regimen, which continued after discharge. Autoantibody detection tests for DM were negative and they were diagnosed with DM induced by ICIs, pembrolizumab in two of them, and nivolumab in another. The purpose of this case report is to show the development of DM1 in an acute form in patients treated with PD-1 inhibitors. Based on these cases and the reviewed literature, we seek to identify clinical characteristics and suggest strategies for the proper identification, control, treatment, and follow-up of patients treated with ICIs to minimize the impact of autoimmune dysfunction.

Isoinmunización Rh en bajas respondedoras: Reporte de caso / Rh Isoimmunization in Low Responders: Case Report / Isoimunização Rh em pacientes com baixa resposta: relato de caso

Introducción. La isoinmunización Rh consiste en la producción de anticuerpos maternos en una gestante Rh negativa contra los antígenos de los eritrocitos Rh positivos fetales ocasionados por una hemorragia fetomaterna. En población gestante, el 15% son Rh negativo y la severidad de la afectación fetal está relacionada con una serie de procesos inmunológicos y la historia obstétrica. Si una gestante Rh negativa con riesgo de isoinmunización no recibe profilaxis con inmunoglobulina Anti-D se inmuniza el 16% en la primera gestación, el 30% en la segunda y el 50% después de la tercera. Con este reporte de caso queremos describir el subgrupo de pacientes gestantes con isoinmunización Rh bajas respondedoras. Presentación del caso. G9P5C1A2Gem1V7 de 43 años, remitida en semana 30 de gestación por isoinmunización Rh, no recibió inmunoglobulina Anti-D durante este embarazo, ni en los anteriores ni en el posparto, reporte de Coombs indirecto de 1/4 que se eleva a 1/16, seguimiento ecográfico normal. En semana 35.3 presenta anemia fetal leve y por tratarse de un embarazo alrededor del término se finaliza por cesárea. Recién nacido con adecuado peso para la edad gestacional, quien fue dado de alta a las 72 horas con evolución satisfactoria. Discusión. Las gestantes con isoinmunización Rh bajas respondedoras se sensibilizan con altos volúmenes sanguíneos sin repercusión hemodinámica in utero, produciendo una enfermedad hemolítica fetal leve. Esta respuesta inmune es poco frecuente y está asociada a factores protectores; sin embargo, son necesarios más estudios que sustenten esta condición. Conclusiones. El control prenatal y el Coombs indirecto cuantitativo seriado son las principales herramientas para la prevención de la isoinmunización. El conocimiento de la respuesta inmunológica permite identificar el subgrupo de las bajas respondedoras que tienen una evolución clínica más leve y menor morbilidad neonatal. Palabras clave: Embarazo; Isoinmunización Rh; Eritroblastosis Fetal; Globulina Inmune RHO(D); Hidropesía Fetal.

Introduction. Rh isoimmunization consists of a Rh-negative pregnant woman producing maternal antibodies against the antigens of fetal Rh-positive erythrocytes due to fetomaternal hemorrhage. 15% of the pregnant population is Rh negative, and the severity of fetal effects is related to a series of immunological processes and the obstetric history. If a Rh-negative pregnant woman at risk of isoimmunization does not receive a prophylaxis of Anti-D immunolobulin, 16% are immunized in the first pregnancy, 30% in the second and 50% after the third. In this case report we will describe the subgroup of low responder pregnant patients with Rh isoimmunization. Case Presentation. G9P5C1A2Gem1V7, 43 years old, referred on the 30th week of pregnancy due to Rh isoimmunization. She did not receive Anti-D immunolobulin during this pregnancy, nor in her previous pregnancies, nor during postpartum. Indirect Coombs report of 1/4, which increases to 1/16. Ultrasound monitoring is normal. At week 35.3 she presented mild fetal anemia, and because the pregnancy was near its term, it was ended by cesarean section. Newborn with adequate weight considering the gestational age, who was then discharged after 72 hours with satisfactory evolution. Discussion. Low responder pregnant women with Rh isoimmunization are sensitized with high blood volumes but without hemodynamic repercussions in utero, producing a mild fetal hemolytic disease. This immune response is infrequent and is associated with protective factors; however, further studies are required to support this condition. Conclusions. Prenatal control and serialized quantitative indirect Coombs testing are the main tools for the prevention of isoimmunization. Knowledge of the immunological response enables identifying the subgroup of low responders who present a milder clinical evolution and lower newborn morbidity. Keywords: Pregnancy; Rh Isoimmunization; Erythroblastosis, Fetal; RHO(D) Immune Globulin; Hydrops Fetalis.

Introdução. A isoimunização Rh consiste na produção de anticorpos maternos em uma gestante Rh negativa contra os antígenos dos eritrócitos fetais Rh positivos causados por hemorragia fetomaterna. Na população gestante, 15% são Rh negativos e a gravidade do envolvimento fetal está relacionada a uma série de processos imunológicos e ao histórico obstétrico. Se uma gestante Rh negativa com risco de isoimunização não receber profilaxia com imunoglobulina Anti-D, imuniza-se 16% na primeira gestação, 30% na segunda e 50% após a terceira. Com este relato de caso, queremos descrever o subgrupo de pacientes gestantes com isoimunização Rh de baixa resposta. Apresentação do caso. G9P5C1A2Gem1V7, 43 anos, encaminhada na 30ª semana de gestação para isoimunização Rh, não recebeu imunoglobulina Anti-D nesta gestação, nem nas anteriores nem no puerpério, laudo de Coombs indireto de 1/4 que sobe para 1/16, acompanhamento ultrassonográfico normal. Na semana 35,3, apresentou anemia fetal leve e por se tratar de uma gestação próxima ao termo, foi interrompida por cesariana. Recém-nascido com peso adequado para a idade gestacional, que recebeu alta às 72 horas com evolução satisfatória. Discussão. Gestantes com isoimunização Rh de baixa resposta são sensibilizadas com elevados volumes sanguíneos sem repercussões hemodinâmicas in utero, produzindo doença hemolítica fetal leve. Essa resposta imune é rara e está associada a fatores protetores; no entanto, mais estudos são necessários para fundamentar esta condição. Conclusões. O controle pré-natal e o Coombs indireto quantitativo seriado são as principais ferramentas para a prevenção da isoimunização. O conhecimento da resposta imunológica permite identificar o subgrupo de pacientes com baixa resposta que apresentam evolução clínica mais branda e menor morbidade neonatal. Palavras-chave: Gravidez; Isoimunização Rh; Eritroblastose Fetal; Inmunoglobulina RHO (D), Hidropisia Fetal.

Trends of humoral immune responses to heterologous antigenic exposure due to vaccination & omicron SARS-CoV-2 infection: Implications for boosting

Background & objectives: Vaccination and natural infection can both augment the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how omicron infection has affected the vaccine-induced and hybrid immunity is not well studied in Indian population. The present study was aimed to assess the durability and change in responses of humoral immunity with age, prior natural infection, vaccine type and duration with a minimum gap of six months post-two doses with either ChAdOx1 nCov-19 or BBV152 prior- and post-emergence of the omicron variant. Methods: A total of 1300 participants were included in this observational study between November 2021 and May 2022. Participants had completed at least six months after vaccination (2 doses) with either ChAdOx1 nCoV-19 or an inactivated whole virus vaccine BBV152. They were grouped according to their age (? or ?60 yr) and prior exposure of SARS-CoV-2 infection. Five hundred and sixteen of these participants were followed up after emergence of the Omicron variant. The main outcome was durability and augmentation of the humoral immune response as determined by anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentrations, anti-nucleocapsid antibodies and anti-omicron RBD antibodies. Live virus neutralization assay was conducted for neutralizing antibodies against four variants – ancestral, delta and omicron and omicron sublineage BA.5. Results: Before the omicron surge, serum anti-RBD IgG antibodies were detected in 87 per cent participants after a median gap of eight months from the second vaccine dose, with a median titre of 114 [interquartile range (IQR) 32, 302] BAU/ml. The levels increased to 594 (252, 1230) BAU/ml post- omicron surge (P<0.001) with 97 per cent participants having detectable antibodies, although only 40 had symptomatic infection during the omicron surge irrespective of vaccine type and previous history of infection. Those with prior natural infection and vaccination had higher anti-RBD IgG titre at baseline, which increased further [352 (IQR 131, 869) to 816 (IQR 383, 2001) BAU/ml] (P<0.001). The antibody levels remained elevated after a mean time gap of 10 months, although there was a decline of 41 per cent. The geometric mean titre was 452.54, 172.80, 83.1 and 76.99 against the ancestral, delta, omicron and omicron BA.5 variants in the live virus neutralization assay. Interpretation & conclusions: Anti-RBD IgG antibodies were detected in 85 per cent of participants after a median gap of eight months following the second vaccine dose. Omicron infection probably resulted in a substantial proportion of asymptomatic infection in the first four months in our study population and boosted the vaccine-induced humoral immune response, which declined but still remained durable over 10 months