Contribution of memory T cells to the generation of long-lasting immunity against COVID-19.

Humans are exposed every day to innumerable external stimuli, both environmental and microbial. Immunological memory recalls each specific stimulus and mounts a secondary response that is faster and of a larger magnitude than the primary response; this process constitutes the basis for vaccine development. The COVID-19 pandemic offers a unique opportunity to study the development of immune memory against an emergent microorganism. Memory T cells have an important role in the resolution of COVID-19, and they are key pillars of immunological memory. In this review, we summarize the main findings regarding anti-SARS-CoV-2 memory T cells after infection, after vaccination, and after the combination of these two events ("hybrid immunity"), and analyze how these cells can contribute to long-term protection against the infection with SARS-CoV-2 variants.

Los humanos se exponen cada día a innumerables estímulos externos, tanto ambientales como microbianos. La memoria inmunológica registra de manera específica un estímulo y articula una respuesta secundaria más rápida y de mayor magnitud que la respuesta primaria; este proceso constituye la base del desarrollo de vacunas. La pandemia de COVID-19 ofreció la oportunidad de estudiar el desarrollo de la memoria inmunológica contra un microorganismo emergente. Las células T de memoria tienen un papel importante en la resolución de COVID-19 y son pilares importantes de la memoria inmunológica. En esta revisión se resumen los principales hallazgos de la respuesta de las células T de memoria contra la infección por SARS-CoV-2, a la vacunación o a la combinación de ambos procesos ("inmunidad híbrida"), y se discute cómo estas células pueden contribuir a la protección a largo plazo contra distintas variantes del virus.

Predominance of CD137+ And TNF-α Expressing CD8+ Central Memory T Cells in Mild COVID-19 Recovered Patients Upon SARS-CoV-2 Re-Exposure.

INTRODUCTION: Memory CD8+ T cells are essential for long-term immune protection in viral infections, including COVID-19. METHODS: This study examined the responses of CD8+ TEM, TEMRA, and TCM subsets from unvaccinated individuals who had recovered from mild and severe COVID-19 by flow cytometry. RESULTS AND DISCUSSION: The peptides triggered a higher frequency of CD8+ TCM cells in the recovered mild group. CD8+ TCM and TEM cells showed heterogeneity in CD137 expression between evaluated groups. In addition, a predominance of CD137 expression in naïve CD8+ T cells, TCM, and TEM was observed in the mild recovered group when stimulated with peptides. Furthermore, CD8+ TCM and TEM cell subsets from mild recovered volunteers had higher TNF-α expression. In contrast, the expression partner of IFN-γ, IL-10, and IL-17 indicated an antiviral signature by CD8+ TEMRA cells. These findings underscore the distinct functional capabilities of each memory T cell subset in individuals who have recovered from COVID-19 upon re-exposure to SARS-CoV-2 antigens.

Pooled Cohort Profile: ReCoDID Consortium's Harmonized Acute Febrile Illness Arbovirus Meta-Cohort.

Infectious disease (ID) cohorts are key to advancing public health surveillance, public policies, and pandemic responses. Unfortunately, ID cohorts often lack funding to store and share clinical-epidemiological (CE) data and high-dimensional laboratory (HDL) data long term, which is evident when the link between these data elements is not kept up to date. This becomes particularly apparent when smaller cohorts fail to successfully address the initial scientific objectives due to limited case numbers, which also limits the potential to pool these studies to monitor long-term cross-disease interactions within and across populations. CE data from 9 arbovirus (arthropod-borne viruses) cohorts in Latin America were retrospectively harmonized using the Maelstrom Research methodology and standardized to Clinical Data Interchange Standards Consortium (CDISC). We created a harmonized and standardized meta-cohort that contains CE and HDL data from 9 arbovirus studies from Latin America. To facilitate advancements in cross-population inference and reuse of cohort data, the Reconciliation of Cohort Data for Infectious Diseases (ReCoDID) Consortium harmonized and standardized CE and HDL from 9 arbovirus cohorts into 1 meta-cohort. Interested parties will be able to access data dictionaries that include information on variables across the data sets via Bio Studies. After consultation with each cohort, linked harmonized and curated human cohort data (CE and HDL) will be made accessible through the European Genome-phenome Archive platform to data users after their requests are evaluated by the ReCoDID Data Access Committee. This meta-cohort can facilitate various joint research projects (eg, on immunological interactions between sequential flavivirus infections and for the evaluation of potential biomarkers for severe arboviral disease).

Lymphocyte to High-density Lipoprotein Cholesterol Ratio is Positively Associated with Pre-diabetes, Metabolic Syndrome, and Non-traditional Cardiometabolic Risk Markers: A Cross-sectional Study at Secondary Health Care.

High scores of lymphocyte-to-high-density lipoprotein cholesterol ratio (lymphocyte-to-HDL-c) may be a new indicator of inflammation and metabolic syndrome. Here, we investigated the associations of the lymphocyte-to-HDL-c with traditional and non-traditional cardiometabolic risk markers in subjects at high cardiovascular risk. This study is a cross-sectional analysis with subjects assisted in a Secondary Health Care (n = 581, age = 63.06 ± 13.86 years; 52.3% women). Lymphocyte-to-HDL-c ratio were assessed by routine laboratory tests. Anthropometric and/or biochemical variables were used to calculate traditional (body mass index - BMI, and waist-to-height ratio - WHtR) and non-traditional (lipid accumulation product index-LAP, visceral adiposity index-VAI, deep-abdominal-adipose-tissue index-DAAT, atherogenic index of plasma-AIP, and waist-hypertriglyceridemic phenotype-HTGW) cardiometabolic risk markers. Furthermore, anthropometric measurement waist circumference (WC), blood pressure, metabolic syndrome (MS), and biochemical markers (lipid and glycemic profile) were considered traditional markers of cardiometabolic risk. Pearson's chi-square test, Poisson regression with robust variance, or multinomial logistic regression were performed (α = 0.05). Individuals with a high lymphocyte-HDL-c ratio (> 0.84, 3rd tertile) were associated with the HTGW phenotype, high VAI, high LAP, hypertriglyceridemia, high AIP, high very low-density lipoprotein-cholesterol (VLDL-c), pre-diabetes, and 3 and 4 MS components compared with individuals in the first tertile, independent of confounders. Our findings supported the lymphocyte-to-HDL-c ratio as a potential biomarker during the screening of subjects at high cardiovascular risk.

HIV-Induced Thymic Insufficiency and Aging-Related Immunosenescence on Immune Reconstitution in ART-Treated Patients.

The mechanisms underlying unsatisfactory immune reconstitution in HIV-1 positive patients under ART have not been fully elucidated, even after years of investigation. Thus, this study aimed to assess the correlation between age and thymic production profile, and its influence on inadequate immunological recovery. Here, 44 ART-treated patients with undetectable plasma HIV-1 load (<40 copies/mL) were classified as 31 immunological responders (IR) and 13 immunological non-responders (INR), according to their CD4+ T-cell count after 18 months of ART. The thymic function was assessed by identifying recent thymic emigrants (RTEs) CD4+ T cells (CD4+/CD45RA+CD31+) in PBMCs using flow cytometry. Clinical data were also analyzed from medical records. The INR group showed a higher age at ART initiation (41 ± 3.0) compared to the IR (33.7 ± 2.1) group (p = 0.041). Evaluating RTE CD4+ T-cells, we observed a lower percentage in the INR group (19.5 ± 6.3) compared to the IR group (29.9 ± 11.5) (p = 0.012). There was a strong negative correlation between age at ART initiation and RTE CD4+ T-cells in INRs (r = -0.784, p = 0.004). Our study has highlighted the thymic insufficiency and aging-related immunosenescence with unsatisfactory immunological recovery during ART in HIV-1 positive patients.

Feline leishmaniasis in an animal shelter in northeastern Brazil: Clinical aspects, coinfections, molecular detection, and serological study of a new recombinant protein.

Infection and clinical cases of leishmaniasis caused by Leishmania infantum in cats have been increasingly reported in several countries, including Brazil. In this study, we used an enzyme-linked immunosorbent assay (ELISA) and an immunochromatographic test (ICT) based on a recombinant antigen (rKDDR-plus) to detect anti-Leishmania antibodies in cats from an animal shelter in northeastern Brazil. We compared the results with an ELISA using L. infantum crude antigen (ELISA-CA). We also investigated the presence of Leishmania DNA in blood or ocular conjunctival samples as well as the association between Leishmania PCR positivity and serological positivity to feline immunodeficiency virus (FIV), feline leukemia virus (FeLV) and Toxoplasma gondii. Concerning serological assays, a higher positivity was detected using the ICT-rKDDR-plus (7.5%; 7/93) as compared to ELISA-rKDDR-plus (5.4%; 5/93) and ELISA-CA (4.3%; 4/93). Upon PCR testing, 52.7% (49/93) of the ocular conjunctival swabs and 48.3% (44/91) of the blood samples were positive. Together, PCR and serological testing revealed overall positivities of 73.1% (68/93) and 12.9% (12/93), respectively. Among PCR-positive samples, 45.5% (31/68) showed co-infection with FIV, 17.6% (12/68) with FeLV, and 82.3% (56/68) with T. gondii. More than half of the PCR-positive cats showed at least one clinical sign suggestive of leishmaniasis (58.8%; 40/68) and dermatological signs were the most frequent ones (45.5%; 31/68). Both tests employing the recombinant antigen rKDDR-plus (i.e., ICT-rKDDR-plus and ELISA-rKDDR-plus) detected more positive cats than the ELISA-CA but presented low overall accuracy. PCR testing using either blood or ocular conjunctival samples detected much more positive cats than serological tests.

The spleen is the graveyard of CD4+ cells in patients with immunological failure of visceral leishmaniasis and AIDS.

BACKGROUND: Visceral leishmaniasis (VL), or kala-azar, is a common comorbidity in patients with AIDS in endemic areas. Many patients continue to experiences relapses of VL despite virological control, but with immunological failure. These patients remain chronically symptomatic with hypersplenism, for example with anemia, leukopenia, and thrombocytopenia, and are at risk of severe co-infection due to low CD4+ count. Therefore, in this study, splenectomized patients with VL and HIV infection were investigated to understand why the CD4+ count fails to recover in these patients, evaluating the importance of spleen mass for hypersplenism and immunological failure. METHODS: From a retrospective open cohort of 13 patients who had previously undergone splenectomy as salvage therapy for relapsing VL, 11 patients with HIV infection were investigated. This study compared the patients' complete blood cell count (CBC) and CD4+ and CD8+ cell counts before and after splenectomy with respect to spleen weight. RESULTS: CBC was substantially improved after splenectomy, indicating hypersplenism. However, to the best of our knowledge, this is the first study to show that spleen mass is strongly and negatively correlated with CD4+ cell count (ρ = -0.71, P = 0.015). CONCLUSIONS: This finding was unexpected, as the spleen is the most extensive lymphoid tissue and T-lymphocyte source. After reviewing the literature and reasoning, we hypothesized that the immunological failure was secondary to CD4+ loss initially by apoptosis in the spleen induced by productive HIV infection and, subsequently, by pyroptosis sustained by parasitic infection in spleen macrophages.

HPV and Cervical Cancer: Molecular and Immunological Aspects, Epidemiology and Effect of Vaccination in Latin American Women.

Cervical cancer is primarily caused by Human Papillomavirus (HPV) infection and remains a significant public health concern, particularly in Latin American regions. This comprehensive narrative review addresses the relationship between Human Papillomavirus (HPV) and cervical cancer, focusing on Latin American women. It explores molecular and immunological aspects of HPV infection, its role in cervical cancer development, and the epidemiology in this region, highlighting the prevalence and diversity of HPV genotypes. The impact of vaccination initiatives on cervical cancer rates in Latin America is critically evaluated. The advent of HPV vaccines has presented a significant tool in combating the burden of this malignancy, with notable successes observed in various countries, the latter due to their impact on immune responses. The review synthesizes current knowledge, emphasizes the importance of continued research and strategies for cervical cancer prevention, and underscores the need for ongoing efforts in this field.

Inducción de tolerancia inmune en menores de 18 años con hemofilia A: experiencia en Uruguay, 2009-2020 / Induction of immune tolerance in children of under 18 years of age with hemophilia A: experience in uruguay, 2009-2020 / Indução de tolerância imune em crianças menores de 18 anos com hemofilia A: experiência no uruguai, 2009-2020

Introducción: el desarrollo de inhibidores contra el factor VIII (FVIII) es la complicación más seria del tratamiento en la hemofilia A. La inducción de tolerancia inmune (ITI) permite utilizar nuevamente el concentrado de FVIII para profilaxis o tratamiento. Objetivos: describir la experiencia con la ITI en menores de 18 años con hemofilia A severa (HAS) en un prestador integral de salud pública. Material y métodos: estudio descriptivo, retrospectivo, de menores de 18 años con HAS, concentraciones de inhibidores de FVIII ≥ a 5 UB, a quienes se les realizó ITI y seguimiento completo entre 2009 y 2020. Para la ITI se utilizó concentrado de FVIII derivado plasmático. El beneficio se expresa como la tasa de éxito definido por la negativización del inhibidor. Resultados: se incluyeron seis pacientes. Edad promedio al diagnóstico de inhibidor 2,96 años, luego de 24,4 días de exposición (DDE) a concentrados de FVIII. Media de inicio de ITI 3,76 niños y el tiempo de latencia del diagnóstico de inhibidor y el inicio de la ITI fue de 10,33 meses. El pico máximo del título pre-ITI fue en promedio de 114,7 UB. Cuatro pacientes iniciaron el régimen de ITI con títulos de inhibidor menor a 10 UB. El título del inhibidor se negativizó en 8,2 meses y el porcentaje de recuperación in vivo >65% se logró con una media de 15,7 meses. La ITI fue exitosa en 83% de los casos. Conclusiones: en niños con hemofilia A e inhibidores de alto título, la ITI tiene un elevado éxito, tal como ocurrió en esta serie. Dado que el tiempo de respuesta es variable, la ITI debe ser individualizada.

Introduction: the development of inhibitors against factor VIII is the most serious complication of treatment in hemophilia A. Immune tolerance induction (ITI) enables the factor VIII concentrate to be used again for prophylaxis or treatment. Objectives: describe the experience with ITI in children of under 18 years of age with severe hemophilia A (SAH) in a health care provider. Material and methods: descriptive, retrospective study of children under 18 years of age with SAH, concentrations of FVIII inhibitors ≥ 5BU, who underwent ITI and full follow-up between 2009-2020. For ITI, we used plasma derived FVIII concentrate. The benefit is expressed as the success rate defined by the inhibitor's negativization. Results: 6 patients were included. Mean age at diagnosis of inhibitor 2,96 years, after 24,4 days of exposure (DAE) to FVIII concentrates. Mean ITI onset was 3,76 years and latency time from inhibitor diagnosis and ITI onset was 10,33 months. Maximum peak of the pre ITI title was an average of 114,7 UB. Four patients started the ITI regimen with inhibitors titers less than 10 BU. The inhibitor titer negative in 8,2 months and in vivo recovery rate >65% was achieved with a mean of 15,7 months. The ITI was successful in 83% of the cases. Conclusions: ITI is highly successful in children with hemophilia A and high-titer inhibitors, as this case suggests. Since the response time is variable, the ITI must be individualized.

Introdução: o desenvolvimento de inibidores contra o fator VIII é a complicação mais grave do tratamento da hemofilia A. A indução de tolerância imunológica (ITI) permite que o concentrado de fator VIII seja novamente utilizado para profilaxia ou tratamento. Objetivos: descrever a experiência com ITI em crianças menores de 18 anos com hemofilia A grave (HAS) em um serviço de saúde pública abrangente. Material e métodos: estudo descritivo e retrospectivo de crianças menores de 18 anos com HAS, concentrações de inibidor do FVIII ≥ 5 BU), que realizaram ITI e acompanhamento completo entre 2009-2020. Concentrado de FVIII derivado de plasma foi utilizado para ITI. O benefício é expresso como a taxa de sucesso definida pela negativação do inibidor. Resultados: 6 pacientes foram incluídos. Idade média no diagnóstico do inibidor 2,96 anos, após 24,4 dias de exposição (DDE) a concentrados de FVIII. A média de início da ITI foi de 3,76 crianças e o tempo de latência do diagnóstico do inibidor e início da ITI foi de 10,33 meses. O pico máximo do título pré-ITI foi em média 114,7 BU. Quatro pacientes iniciaram o regime ITI com títulos de inibidor inferiores a 10 BU. O título do inibidor tornou-se negativo em 8,2 meses e a percentagem de recuperação in vivo >65% foi alcançada com uma média de 15,7 meses. O ITI foi bem-sucedido em 83% dos casos. Conclusões: em crianças com hemofilia A e inibidores de títulos elevados, a ITI é altamente bem sucedida, como ocorreu nesta série. Como o tempo de resposta é variável, o ITI deve ser individualizado.

New Immunological Markers in Chromoblastomycosis-The Importance of PD-1 and PD-L1 Molecules in Human Infection.

The pathogenesis of chromoblastomycosis (CBM) is associated with Th2 and/or T regulatory immune responses, while resistance is associated with a Th1 response. However, even in the presence of IFN-γ, fungi persist in the lesions, and the reason for this persistence is unknown. To clarify the factors associated with pathogenesis, this study aimed to determine the polarization of the cellular immune response and the densities of cells that express markers of exhaustion in the skin of CBM patients. In the skin of patients with CBM, a moderate inflammatory infiltrate was observed, characterized primarily by the occurrence of histiocytes. Analysis of fungal density allowed us to divide patients into groups that exhibited low and high fungal densities; however, the intensity of the inflammatory response was not related to mycotic loads. Furthermore, patients with CBM exhibited a significant increase in the number of CD4+ and CD8+ cells associated with a high density of IL-10-, IL-17-, and IFN-γ-producing cells, indicating the presence of a chronic and mixed cellular immune response, which was also independent of fungal load. A significant increase in the number of PD-1+ and PD-L1+ cells was observed, which may be associated with the maintenance of the fungus in the skin and the progression of the disease.

Surface immunogenic protein from Streptococcus agalactiae and Fissurella latimarginata hemocyanin are TLR4 ligands and activate MyD88- and TRIF dependent signaling pathways.

The development of vaccine adjuvants is of interest for the management of chronic diseases, cancer, and future pandemics. Therefore, the role of Toll-like receptors (TLRs) in the effects of vaccine adjuvants has been investigated. TLR4 ligand-based adjuvants are the most frequently used adjuvants for human vaccines. Among TLR family members, TLR4 has unique dual signaling capabilities due to the recruitment of two adapter proteins, myeloid differentiation marker 88 (MyD88) and interferon-ß adapter inducer containing the toll-interleukin-1 receptor (TIR) domain (TRIF). MyD88-mediated signaling triggers a proinflammatory innate immune response, while TRIF-mediated signaling leads to an adaptive immune response. Most studies have used lipopolysaccharide-based ligands as TLR4 ligand-based adjuvants; however, although protein-based ligands have been proven advantageous as adjuvants, their mechanisms of action, including their ability to undergo structural modifications to achieve optimal immunogenicity, have been explored less thoroughly. In this work, we characterized the effects of two protein-based adjuvants (PBAs) on TLR4 signaling via the recruitment of MyD88 and TRIF. As models of TLR4-PBAs, we used hemocyanin from Fissurella latimarginata (FLH) and a recombinant surface immunogenic protein (rSIP) from Streptococcus agalactiae. We determined that rSIP and FLH are partial TLR4 agonists, and depending on the protein agonist used, TLR4 has a unique bias toward the TRIF or MyD88 pathway. Furthermore, when characterizing gene products with MyD88 and TRIF pathway-dependent expression, differences in TLR4-associated signaling were observed. rSIP and FLH require MyD88 and TRIF to activate nuclear factor kappa beta (NF-κB) and interferon regulatory factor (IRF). However, rSIP and FLH have a specific pattern of interleukin 6 (IL-6) and interferon gamma-induced protein 10 (IP-10) secretion associated with MyD88 and TRIF recruitment. Functionally, rSIP and FLH promote antigen cross-presentation in a manner dependent on TLR4, MyD88 and TRIF signaling. However, FLH activates a specific TRIF-dependent signaling pathway associated with cytokine expression and a pathway dependent on MyD88 and TRIF recruitment for antigen cross-presentation. Finally, this work supports the use of these TLR4-PBAs as clinically useful vaccine adjuvants that selectively activate TRIF- and MyD88-dependent signaling to drive safe innate immune responses and vigorous Th1 adaptive immune responses.

Prevalence and incidence of canine visceral leishmaniasis and its clinical-immunological features in an endemic area of the Brazilian Amazon.

BACKGROUND: A cohort study for 2 years period analysed the prevalence, incidence and clinical-immunological features of canine Leishmania (L.) chagasi-infection in 316 mongrel dogs in a visceral leishmaniasis-endemic area in Pará State, Brazil. OBJECTIVE/METHODS: Diagnosis of infection was performed by the indirect fluorescent antibody test (IFAT-IgG), the leishmanin skin test (LST) and a parasite search (from the popliteal lymph node aspiration) at the beginning of the study and at 6, 12 and 24 months intervals. RESULTS: IFAT/LST revealed three immune profiles of infection: (I) IFAT(+) /LST(-) (81), (II) IFAT(-) /LST(+) (17) and (III) IFAT(+) /LST(+) (13). Prevalence of profiles I, II and III were 25.6, 5.4 and 4.1%, and an overall prevalence 35.1%. Incidence of profiles I, II and III were 5.4, 0.3 and 0.0%, and an overall incidence 5.7% dogs per month. Incidence at the age ranges <1 year, ≥1 year, <7 years and ≥7 years evidenced a highest rate in the age range <1 year (6.6% dogs per month). Parasitological diagnosis was positive in 19% dogs at the prevalence (85.7% profile I), and in 11% at the incidence (100% profile I). The clinical picture of 179 infected dogs showed 145 (81%) of profile I (82% subclinical); 21 (11.7%) of profile II (100% subclinical); and 13 (7.3%) of profile III (84.6% subclinical). Conversion from subclinical to sick dogs was higher (p < 0.05) in profile I (40.2%) than in profiles II (5.8%) and III (9%). Immunological conversion showed that only 3.2% of profile I dogs (prevalence) converted to LST(+) (two at the end of the first 6 months and 1 after 24 months), while 82.3% of profile II dogs converted to IFAT(+) (11 in the first 6 months, whereas three after 12 months). A 100% death rate was observed in dogs from profile I alone. CONCLUSION: These results reinforce the need of adopting preventive strategies against CVL as early as in the first semester of the dog's life.

Immune response modulation in inflammatory bowel diseases by Helicobacter pylori infection.

Many studies point to an association between Helicobacter pylori (H. pylori) infection and inflammatory bowel diseases (IBD). Although controversial, this association indicates that the presence of the bacterium somehow affects the course of IBD. It appears that H. pylori infection influences IBD through changes in the diversity of the gut microbiota, and hence in local chemical characteristics, and alteration in the pattern of gut immune response. The gut immune response appears to be modulated by H. pylori infection towards a less aggressive inflammatory response and the establishment of a targeted response to tissue repair. Therefore, a T helper 2 (Th2)/macrophage M2 response is stimulated, while the Th1/macrophage M1 response is suppressed. The immunomodulation appears to be associated with intrinsic factors of the bacteria, such as virulence factors - such oncogenic protein cytotoxin-associated antigen A, proteins such H. pylori neutrophil-activating protein, but also with microenvironmental changes that favor permanence of H. pylori in the stomach. These changes include the increase of gastric mucosal pH by urease activity, and suppression of the stomach immune response promoted by evasion mechanisms of the bacterium. Furthermore, there is a causal relationship between H. pylori infection and components of the innate immunity such as the NLR family pyrin domain containing 3 inflammasome that directs IBD toward a better prognosis.

Enfermedad periodontal y su relación con la diabetes

La diabetes mellitus es una enfermedad sistémica padecida en la actualidad por gran parte de la población. Padecer una enfermedad sistémica predispone la aparición de enfermedades periodontales. La gravedad de la enfermedad periodontal está afectada por la respuesta inflamatoria. Células como IL-1β, IL-6 y TNF-α se elevan de forma crónica y persistente. La enfermedad periodontal prevalente en el paciente diabético suele ser la periodontitis por enfermedades sistémicas. Se observan ciertas afectaciones en ligamentos y hueso (deterioro o pérdida), por lo que resulta importante que el odontólogo conozca todo lo que involucra la enfermedad periodontal en un paciente diabético. Para la presente investigación se realizó una revisión bibliográfica en importantes bases de datos como: Pubmed y Scopus. El objetivo propuesto fue: establecer la interrelación entre las enfermedades periodontales y la diabetes y determinar entre las enfermedades periodontales la de mayor prevalencia en pacientes diabéticos.

Diabetes mellitus is a systemic disease currently suffered by a large part of the population. Having a systemic disease predisposes the appearance of periodontal diseases. The severity of periodontal disease is affected by the inflammatory response. Cells such as IL-1β, IL-6, and TNF-α are chronically and persistently elevated. The prevalent periodontal disease in diabetic patients is usually periodontitis due to systemic diseases. Certain affectations are observed in ligaments and bone (deterioration or loss), so it is important that the dentist knows everything that periodontal disease involves in a diabetic patient. For the present investigation, a bibliographic review was carried out in important databases such as: Pubmed and Scopus. The proposed objective was: to establish the relationship between periodontal diseases and diabetes and to determine the periodontal diseases with the highest prevalence in diabetic patients.

Imunoterapia de dessensibilização para Malassezia spp. - Relato de caso experimental / Desensitization immunotherapy for Malassezia spp: experimental case report

A pitiríase versicolor (PV) consiste em uma infecção fúngica ocasionada por leveduras de Malassezia spp., que apesar de manejo simples, é uma doença com elevadas chances de recidiva e cronificação, além da pouca variedade de terapias efetivas para tratar cepas resistentes. Existem relatos na literatura sobre utilização de dessensibilização para Malassezia spp., mas para o tratamento de dermatite atópica e não PV, conferindo caráter inovador ao relato em questão. O caso apresentado consiste em um paciente de 28 anos, do sexo masculino, com manifestações típicas de PV em região de face, cervical, dorsal e axilar, há 4 anos, com resistência aos esquemas terapêuticos tópicos e sistêmicos. Uma vez identificada a ineficácia das terapias tradicionais, foi iniciado o tratamento com dessensiblização para Malassezia spp., em aplicações semanais, com aumento progressivo da dosagem e posterior aumento no intervalo das aplicações. Após onze meses de realização do novo tratamento, o paciente evoluiu com melhora completa das lesões. Conclui-se que a utilização de técnicas imunoterápicas para o tratamento de PV foi considerado eficaz no caso relatado, apesar de ainda não haver evidências que amparem sua utilização em maior escala.

Pityriasis versicolor is a infection caused by Malassezia yeast species, which, despite simple management, involves a high risk of recurrence and chronicity, and there are few effective therapies for resistant strains. Desensitization for Malassezia spp. has been reported in the literature, but for atopic dermatitis, rather than pityriasis versicolor, making this an innovative report. The case presented herein is of a 28-year-old man who had typical manifestations of pityriasis versicolor in the face, cervical, dorsal, and axillary region for 4 years that were resistant to topical and systemic therapies. Once the ineffectiveness of traditional therapies had been determined, weekly Malassezia desensitization sessions were begun, progressively increasing first in dosage and then in frequency. After 11 months, the lesions had improved completely. In this case, immunotherapeutic techniques effectively treated pityriasis versicolor, although the evidence is as yet insufficient to support large-scale use.

Actualización en marcadores inmunológicos en el estudio de la infección por HIV: aportes desde el laboratorio clínico / Immunological markers in the study of HIV infection: contributions from the clinical laboratory. An update / Atualização em marcadores imunológicos no estudo da infecção pelo HIV: contribuições do laboratório clínico

Resumen Si bien la buena adherencia al tratamiento antirretroviral en la infección por el virus de la inmunodeficiencia humana (HIV por Human Immunodeficiency virus en inglés o VIH, por su sigla en español) demostró una sustancial mejoría clínica en las personas que viven con él, lograr el acceso al tratamiento continúa siendo un desafío en los tiempos que corren. Los estudios de laboratorio para diagnóstico y seguimiento de la infección por HIV se centran en estudios virológicos y recuento de linfocitos CD4+ y CD8+. Sin embargo, no se evalúa de forma detallada el perfil inmunológico de las personas que viven con HIV, ni la reconstitución inmune luego de recibido el tratamiento. Es por ello que el objetivo de esta revisión fue describir, por un lado, los diversos estudios realizados desde el laboratorio para el diagnóstico y seguimiento de la infección por HIV. Por otro lado, describir los aportes del laboratorio bioquímico en el estudio del perfil inmunológico de las personas que viven con HIV, el cual incluye desde determinaciones actualmente en uso, hasta nuevos biomarcadores inflamatorios solubles o de membrana celular, como así también las subpoblaciones linfocitarias. Dichos biomarcadores podrían ser herramientas valiosas como descriptores del estado inmunológico de las personas e, incluso, predictores de patologías asociadas a la infección por HIV.

Abstract Although a correct adherence rate to antiretroviral treatment in human immunodeficiency virus (HIV) infection reveals a substantial clinical improvement in people living with HIV, achieving access to treatment is still challenging. Laboratory studies for diagnosis and follow-up are mainly focused on virological status, CD4+ and CD8+ T cells counts. However, the immunological profile of people living with HIV is not evaluated in detail, neither is the immune reconstitution after treatment. Consequently, the aim of this review was is to describe, on the one hand, the studies carried out in the laboratory for the diagnosis and monitoring of HIV infection, and on the other hand, is to describe the contributions of the biochemical laboratory in the study of the immunological profile of people living with HIV. This study includes determinations currently in use, and the determination of new soluble or cell membrane inflammatory biomarkers, as well as T cell subsets. These biomarkers could be valuable tools as descriptors of the impervious state of people, and even predictors of pathologies associated with HIV infection.

Resumo Embora a boa adesão ao tratamento antirretroviral na infecção pelo vírus da imunodeficiência humana (HIV) tenha demonstrado melhora clínica substancial em pessoas que vivem com HIV, conseguir o acesso ao tratamento continua sendo um desafio nos momentos em que correm. Os estudos laboratoriais para diagnóstico e monitoramento da infecção pelo HIV concentram-se em estudos virológicos e contagem de linfócitos CD4+ e CD8+. No entanto, o perfil imunológico das pessoas que vivem com HIV não é avaliado detalhadamente, nem a reconstituição imunológica após o tratamento. É por isso que o objetivo desta revisão foi descrever, por um lado, os vários estudos realizados em laboratório para o diagnóstico e monitoramento da infecção pelo HIV. Por outro lado, descrever as contribuições do laboratório bioquímico no estudo do perfil imunológico de pessoas que vivem com HIV, que inclui desde determinações atualmente em uso, até novos biomarcadores inflamatórios solúveis ou de membrana celular, bem como subpopulações de linfócitos. Esses biomarcadores podem ser ferramentas valiosas como descritores do estado imunológico das pessoas e até mesmo como preditores de patologias associadas à infecção pelo HIV.

Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients.

Introduction: The aim of the present study was to investigate the association between the single nucleotide polymorphism (SNP) rs1927914 A/G in TLR4 gene and the immunological profile of household contacts (HHC) of leprosy patients. Leprosy classification is usually complex and requires the assessment of several clinical and laboratorial features. Methods: Herein, we have applied distinct models of descriptive analysis to explore qualitative/quantitative changes in chemokine and cytokine production in HHC further categorized according to operational classification [HHC(PB) and HHC(MB)] and according to TLR4SNP. Results and discussion: Our results showed that M. leprae stimuli induced an outstanding production of chemokines (CXCL8;CCL2; CXCL9; CXCL10) by HHC(PB), while increase levels of pro-inflammatory cytokines (IL-6; TNF; IFN-γ; IL-17) were observed for HHC(MB). Moreover, the analysis of chemokine and cytokine signatures demonstrated that A allele was associated with a prominent soluble mediator secretion (CXCL8; CXCL9; IL-6; TNF; IFN-γ). Data analysis according to TLR4 SNP genotypes further demonstrated that AA and AG were associated with a more prominent secretion of soluble mediators as compared to GG, supporting the clustering of AA and AG genotypes into dominant genetic model. CXCL8, IL-6, TNF and IL-17 displayed distinct profiles in HHC(PB) vs HHC(MB) or AA+AG vs GG genotype. In general, chemokine/cytokine networks analysis showed an overall profile of AA+GA-selective (CXCL9-CXCL10) and GG-selective (CXCL10-IL-6) axis regardless of the operational classification. However, mirrored inverted CCL2-IL-10 axis and a (IFN-γ-IL-2)-selective axis were identified in HHC(MB). CXCL8 presented outstanding performance to classify AA+AG from GG genotypes and HHC(PB) from HHC(MB). TNF and IL-17 presented elevated accuracy to classify AA+AG from GG genotypes and HHC(PB) (low levels) from HHC(MB) (high levels), respectively. Our results highlighted that both factors: i) differential exposure to M. leprae and ii) TLR4 rs1927914 genetic background impact the immune response of HHC. Our main results reinforce the relevance of integrated studies of immunological and genetic biomarkers that may have implications to improve the classification and monitoring of HHC in future studies.

Evaluation of Five Non-Culture-Based Methods for the Diagnosis of Meningeal Sporotrichosis.

Sporotrichosis is the main subcutaneous mycosis worldwide. Several complications, including meningeal forms, can be observed in immunocompromised individuals. The sporotrichosis diagnosis is time-consuming due to the culture's limitations. The low fungal burden in cerebrospinal fluid (CSF) samples is another important drawback in the diagnosis of meningeal sporotrichosis. Molecular and immunological tests can improve the detection of Sporothrix spp. in clinical specimens. Therefore, the following five non-culture-based methods were evaluated for the detection of Sporothrix spp. in 30 CSF samples: (i) species-specific polymerase chain reaction (PCR); (ii) nested PCR; (iii) quantitative PCR; (iv) enzyme-linked immunosorbent assay (ELISA) for IgG detection; and (v) ELISA for IgM detection. The species-specific PCR was unsuccessful in the diagnosis of the meningeal sporotrichosis. The other four methods presented substantial levels of sensitivity (78.6% to 92.9%) and specificity (75% to 100%) for the indirect detection of Sporothrix spp. Both DNA-based methods presented similar accuracy (84.6%). Both ELISA methods were concomitantly positive only for patients with sporotrichosis and clinical signs of meningitis. We suggest that these methods should be implemented in clinical practice to detect Sporothrix spp. in CSF early, which may optimize treatment, augment the chances of a cure, and improve the prognosis of affected individuals.

High-Throughput IgG Epitope Mapping of Tetanus Neurotoxin: Implications for Immunotherapy and Vaccine Design.

Tetanus is an acute, fatal disease caused by exotoxins released from Clostridium tetani during infections. A protective humoral immune response can be induced by vaccinations with pediatric and booster combinatorial vaccines that contain inactivated tetanus neurotoxin (TeNT) as a major antigen. Although some epitopes in TeNT have been described using various approaches, a comprehensive list of its antigenic determinants that are involved with immunity has not been elucidated. To this end, a high-resolution analysis of the linear B-cell epitopes in TeNT was performed using antibodies generated in vaccinated children. Two hundred sixty-four peptides that cover the entire coding sequence of the TeNT protein were prepared in situ on a cellulose membrane through SPOT synthesis and probed with sera from children vaccinated (ChVS) with a triple DTP-vaccine to map continuous B-cell epitopes, which were further characterized and validated using immunoassays. Forty-four IgG epitopes were identified. Four (TT-215-218) were chemically synthesized as multiple antigen peptides (MAPs) and used in peptide ELISAs to screen post-pandemic DTP vaccinations. The assay displayed a high performance with high sensitivity (99.99%) and specificity (100%). The complete map of linear IgG epitopes induced by vaccination with inactivated TeNT highlights three key epitopes involved in the efficacy of the vaccine. Antibodies against epitope TT-8/G can block enzymatic activity, and those against epitopes TT-41/G and TT-43/G can interfere with TeNT binding to neuronal cell receptors. We further show that four of the epitopes identified can be employed in peptide ELISAs to assess vaccine coverage. Overall, the data suggest a set of select epitopes to engineer new, directed vaccines.