Seroprevalencia del SARS-CoV-2 en los pacientes con enfermedades inmunomediadas en tratamiento con terapias biológicas y sintéticos dirigidos / Seroprevalence of SARS-CoV-2 antibodies in patients with immune-mediated inflammatory diseases treated with biological and synthetic targeted therapies

INTRODUCCIÓN: La seroprevalencia del SARS-CoV-2 en las enfermedades inflamatorias inmunomediadas (IMID) sigue siendo fuente de controversia. OBJETIVO: Comparar la seroprevalencia de anticuerpos (Ac) anti SARS-CoV-2 en pacientes con IMID en tratamientos con fármacos antirreumáticos modificadores de la enfermedad biológicos (FAMEb) o sintéticos dirigidos (FAMEsd) frente a un grupo de personas sin IMID. MÉTODOS: Estudio de pacientes con IMID y tratamientos con FAMEb y FAMEsd y de individuos sin IMID. Mediante la técnica de inmunoensayo por quimioluminiscencia indirecta, se determinaron las serologías IgG frente al SARS-CoV-2 entre octubre/2020 y mayo/2021. RESULTADOS: Se estudiaron 1.100 sujetos, 550 pacientes con IMID y 550 personas sin IMID. Se observó una seroprevalencia de 16% (88/550) en los pacientes frente a 19,3% (106/550) en el grupo de personas sin IMID, sin significación estadística (OR 0,790 [IC 95% 0,558-1,118]). Comparando los tratamientos con FAMEb o FAMEsd, se observó una tendencia a una menor seroprevalencia con rituximab, en relación con los individuos sin IMID (OR 0,296 [IC 95% 0,0871,007]). Asimismo, se encontró menor seroprevalencia en los pacientes que además de su FAMEb recibían tratamiento con metotrexato, en comparación con el grupo de personas sin IMID (OR 0,432 [IC 95% 0,223-0,835]). CONCLUSIONES: Las IMID en tratamiento con FAMEb o FAMEsd no influyen en la seroprevalencia frente al SARS-CoV-2 de los pacientes. El tratamiento concomitante con metotrexato disminuye de forma significativa la seroprevalencia en estos pacientes.

BACKGROUND: The seroprevalence of SARS-CoV-2 in immunemediated inflammatory diseases (IMID) remains controversial. AIM: To compare the seroprevalence of antibodies (Ab) to SARS-CoV-2 in patients with IMID receiving treatment with biological diseasemodifying antirheumatic drugs (bDMARD) or targeted synthetic (tsDMARD) versus a group of people without IMID. METHODS: Study of patients with IMID and treatments with bDMARD and tsDMARD and individuals without IMID. IgG serology against SARS-CoV-2 was measured using the two-step sandwich immunoassay technique by indirect chemiluminescence between October 2020 and May 2021. RESULTS: A total of 1100 subjects were studied, 550 patients with IMID and 550 persons without IMID. A seroprevalence of 16% (88/550) was observed in patients versus 19.3% (106/550) in the group of people without IMID, without statistical significance (OR 0.790 [95% CI 0.558-1.118]). Comparing the treatments with bD- MARD or tsDMARD, there was a tendency to lower seroprevalence with rituximab, in relation to individuals without IMID (OR 0.296 [95% CI 0.087-1.007]). In addition, lower seroprevalence was found in patients who received methotrexate treatment in addition to their bDMARD, compared to the group of individuals without IMID (OR 0.432 [95% CI 0.223-0.835]). CONCLUSIONS: IMIDs in treatment with bDMARDs or tsDMARDs do not influence the seroprevalence against SARS-CoV-2 in patients. Concomitant treatment with methotrexate significantly decreased seroprevalence in these patients.

Characterization of Dental Surgeons of Pernambuco State in the COVID-19 Pandemic Context: Preliminary Data

Abstract Objective: To present the results of preliminary research on the characterization of dental surgeons in the state of Pernambuco, during a pandemic of COVID-19. Material and Methods: This is a cross-sectional, descriptive, and exploratory study, whose population was composed of dental surgeons with active enrollment in the Regional Dentistry Council of Pernambuco. Data collection was performed using an electronic form and included characterization of professionals (gender, age, time since graduation, marital status, family income and field of work) and health status (vaccination schedule, presence of comorbidities, biosafety knowledge and testing for COVID-19). Preliminary data correspond to the first week of collection, which were analyzed from the frequency, proportions, and measures of central tendency distributions. Results: Of the 363 dental surgeons, for the field of work, 38.6% work in both the public and private sectors. Comorbidities related to the worsening of COVID-19 were identified in 35.0% of participants, 24.5% are not up to date with influenza and hepatitis vaccines, and 79.3% have not been tested for COVID-19. Regarding the biosafety instructions for COVID-19, 30.7% received no training. Conclusion: It is necessary to immunize dental surgeons to prevent immunological diseases and expansion of the testing capacity for COVID-19, especially for professionals belonging to the risk group. In addition to guaranteeing the offer of qualification courses on biosafety, which is essential for the safe resumption of activities.

Plasticity of neutrophils reveals modulatory capacity

Neutrophils are widely known as proinflammatory cells associated with tissue damage and for their early arrival at sites of infection, where they exert their phagocytic activity, release their granule contents, and subsequently die. However, this view has been challenged by emerging evidence that neutrophils have other activities and are not so short-lived. Following activation, neutrophil effector functions include production and release of granule contents, reactive oxygen species (ROS), and neutrophil extracellular traps (NETs). Neutrophils have also been shown to produce a wide range of cytokines that have pro- or anti-inflammatory activity, adding a modulatory role for this cell, previously known as a suicide effector. The presence of cytokines almost always implies intercellular modulation, potentially unmasking interactions of neutrophils with other immune cells. In fact, neutrophils have been found to help B cells and to modulate dendritic cell (DC), macrophage, and T-cell activities. In this review, we describe some ways in which neutrophils influence the inflammatory environment in infection, cancer, and autoimmunity, regulating both innate and adaptive immune responses. These cells can switch phenotypes and exert functions beyond cytotoxicity against invading pathogens, extending the view of neutrophils beyond suicide effectors to include functions as regulatory and suppressor cells.

Deficiência da STAT5B: uma nova síndrome de insensibilidade ao hormônio de crescimento associada a acometimento imunológico / STAT5B deficiency: a new growth hormone insensitivity syndrome associated to immunological dysfunction

Uma nova apresentação da insensibilidade ao hormônio de crescimento (IGH), causada por mutações em homozigose no gene STAT5B (transdutor de sinal e ativador de transcrição tipo 5B), foi caracterizada nos últimos anos. Sua particularidade é a associação com quadros de disfunção imunológica grave, sendo o mais característico a pneumonite intersticial linfocítica. A presença concomitante de doenças crônicas imunológicas pode fazer com que a baixa estatura seja erroneamente considerada uma consequência do quadro clínico, levando ao subdiagnóstico dessa forma de IGH. O objetivo desta revisão é divulgar o conhecimento atual sobre essa rara patologia, facilitando o reconhecimento de pacientes com IGH secundária a mutações no gene STAT5B em ambulatórios de endocrinologia e de outras especialidades.

A new presentation of growth hormone insensitivity (GHI) caused by homozygous mutations in STAT5B (signal transducer and activator of transcription 5B) gene has been characterized in the last years. Its particularity is the association with severe immune dysfunction, especially with lymphocytic interstitial pneumonitis. This may mislead physicians into considering short stature as secondary to chronic immunological disease and consequently into underdiagnosing this form of GHI. The objective of this review is to propagate current knowledge about this rare pathology, facilitating the diagnosis of patients with GHI due to STAT5B mutations in endocrinology and other specialties clinics.

Mecanismos de daño inmunológico / Immune mediated damage

Las fallas en el control de las respuestas inmunes fisiológicas o en la mantención de la tolerancia a lo propio, produce enfermedades en las cuales el mecanismo patogénico primario es inmunológico. Estas respuestas inmunes descontroladas se llaman mecanismo de hipersensibilidad y serán revisadas en este artículo, basándonos en las clasificaciones de Gell y Coombs y la más reciente de los mecanismos de daño mediados por células.

Failure to control physiologic immune responses or to maintain self-tolerance leads to diseases in wich the primary pathogenic mechanism is immunologic. These uncontrolled immune reactions are called hypersensitivity responses, and are reviewed in this article, based upon the Gell and Coombs and the more recent cell-mediated hypersensitivity reactions classifications.

Toll-like receptors in autoimmunity with special reference to systemic lupus erythematosus.

The Toll-like receptor (TLR) family plays a fundamental role in host innate immunity by mounting a rapid and potent inflammatory response to pathogen infection. TLRs recognize distinct microbial components and activate intracellular signaling pathways that induce expression of host inflammatory genes. Several studies have indicated that TLRs are implicated in many inflammatory and immune disorders. Extensive research in the past decade to understand TLR-mediated mechanisms of innate immunity has enabled pharmaceutical companies to begin to develop novel therapeutics for the purpose of controlling an inflammatory disease. The roles of TLRs in the development of autoimmune diseases have been studied. TLR7 and TLR9 have key roles in production of autoantibodies and/or in development of systemic autoimmune disease. It remains to be determined their role in apoptosis, in the pathogenesis of RNA containing immune complexes, differential expression of TLRs by T regulatory cells.

Asma e rinite ocupacionais: visão imunoalérgica / Occupational asthma and rhinitis: immunoallergic view

Objetivo: Revisar as características clínicas e diagnósticas da asma e da rinite ocupacionais, citando dados epidemiológicos e particularidades na terapêutica, com ênfase nos aspectos imunológicos que devem ser consideradas na visão do alergista. Fonte de Dados: Revisamos periódicos específicos na área de alergia e imunologia nos últimos 10 anos (1999-2009), considerando principalmente as publicações em inglês, indexadas no Medline e capítulos de livros. Síntese de Dados: São apresentados os aspectos epidemiológicos, clínicos e diagnósticos das doenças respiratórias ocupacionais alérgicas (asma e rinite), e ainda as dos agentes ocupacionais mais comumente envolvidos, descrevendo resumidamente os mecanismos imunológicos e não imunológicos responsáveis pelo quadro clínico. Conclusões: A maioria dos quadros de asma/rinite ocupacionais envolvem mecanismos imunológicos com ou sem a participação de anticorpos IgE, sendo que os quadros IgE mediados correspondem a menos que 5% do total, o que limita o uso de testes alérgicos no diagnóstico. O padrão ouro para a confirmação diagnóstica seria, portanto a provocação específica que reproduz a exposição no ambiente de trabalho, independentemente do mecanismo envolvido. A abordagem multiprofissional é muitas vezes necessária para restabelecer a qualidade de vida do trabalhador afetado.

Objective: To review the clinical and diagnostic features of occupational asthma and rhinitis, showing epidemiological data and a summarized therapy, with emphasis on immunological aspects that should be considered in view of the allergist. Sources of data: The author reviewed specific journals in the field of allergy and immunology in the last 10 years (1999-2009), considering the publications in english, indexed in Medline and also book chapters. Summary of data: The author reported epidemiological, clinical and diagnostic data of work-related allergic respiratory diseases (asthma and rhinitis), and also the characteristics of the most commonly involved occupational agents, describing briefly the immunological and not immunological mechanisms responsible for the cases. Conclusions: Most of the cases of occupational asthma/rhinitis involve immunological mechanisms with or without the participation of IgE antibodies, and the IgE-mediated cases correspond to less than 5% of the total, which limits the use of allergy tests in the diagnosis. The gold standard for diagnostic confirmation is therefore the specific challenge tests that intend to reproduce the exposure in the workplace, regardless of the mechanism involved. A multidisciplinary approach is often necessary to restore the quality of life of the affected workers.

Aloimunização: [revisão] / Alloimmunization: [review]

Aloimunização é a formação de anticorpos quando há a exposição do indivíduo a antígenos não próprios, como ocorre, por exemplo, na transfusão de sangue incompatível e nas gestantes, cujos fetos expressam em suas células sanguíneas antígenos exclusivamente de origem paterna. Este artigo se restringe à aloimunização contra antígenos eritrocitários em pacientes obstétricas. Quase todos os anticorpos antieritrocitários podem ser enquadrados em um dos 29 sistemas de grupos sanguíneos já reconhecidos, sendo os mais comumente implicados na doença hemolítica perinatal o anti-D, anti-c e anti-Kell, seguidos por anti-C, anti-E, anti e, anti-Fyª e anti-Jkª. A pesquisa de anticorpos irregulares permite o diagnóstico de indivíduos aloimunizados e modernas técnicas genéticas têm melhor caracterizado estas pacientes para a profilaxia e segmento pré-natal. O tradicional acompanhamento das gestações de risco para a doença hemolítica perinatal, com a espectrofotometria do líquido amniótico e a transfusão intraperitoneal, vem rapidamente sendo substituído pela doplervelocimetria na artéria cerebral média e a transfusão intravascular guiada por ultrassonografia em tempo real. É possível também citar como avanços melhorias nos materiais e na qualidade do sangue transfundido, que, em conjunto, têm elevado a sobrevivência de fetos acometidos. Indubitavelmente, a correta aplicação da profilaxia com uso do anti-D é exitosa com potencial para reduzir os casos de aloimunização.

Alloimmunization is the formation of antibodies when there is an exposition of the individual to non-self antigens, as it occurs, for example, in the transfusion of incompatible blood and pregnancies, in whom the fetus express in its sanguineous cells antigens exclusively of paternal origin. This article is restricted to the alloimmunization against erythrocytes antigens in obstetric patients. Almost all the anti-erythrocytes antibodies can be fit in one of the 29 systems of already recognized sanguineous groups, being more implied in the hemolytic disease of the newborn anti-D, anti-c and anti-Kell, followed by anti-C, anti-E, anti e, anti-Fyª and anti-Jkª. The research of irregular antibodies, to permit the diagnosis of alloimmunizated people, and the modern genetic techniques have better characterized these patients for the prophylaxis and prenatal segment. The traditional accompaniment of the gestations of risk for hemolytic disease of the newborn, with the spectral analysis of the amniotic liquid and the intraperitoneal transfusion, has being quickly substituted for the Doppler ultrasound evaluation in the middle cerebral artery, the intravascular transfusion guided for ultrasonography in real time, beyond improvements in the materials and the quality of the blood, that in set, have raised the survival of the attempting fetus. Doubtlessly, the correct application of the prophylaxis with use of anti-D is successful with potential to reduce the alloimmunization cases.

La inmunología clínica actual: una perspectiva genética y molecular / Present time clinical immunology: a genetic and molecular perspective

During the last few decades, basic scientists and clinicians have gained a deeper insight of the cellular and molecular physiology of the immune system. The widespread application of molecular biology and genetic techniques has advanced our understanding of states of health and disease, bringing forth renewed hopes concerning the advent of a more ÒspecificÓ therapeutic era of clinical immunology. The precise structural and genetic characterization of molecular complexes such as B and T-cell receptors, the Major Histocompatibility Complex (MHC), cytokines, chemokines, cellular receptors and co-receptors has produced a wealth of information open to both diagnostic and therapeutic purposes. We herein review several recent advances in the molecular and genetic characterization of immune deficiency states, autoimmunity and the induction of antigen specific immune unresponsiveness or tolerance, together with the therapeutic implications of these findings

Ultramicrometodo inmunocitoquimico. Titulacion de anticuerpos utilizados para el inmunofenotipaje celular

Se describe el procedimiento para la titulacion de los anticuerpos primarios y los antisueros conjugados, que hizo posible la introduccion en el Instituto de Hematologia Inmunologia, de un ultrametodo inmunocitoquimico para el estudio del inmunofenotipo en enfermedades inmunologicas y en las hemopatias malignas. Este metodo emplea celulas no deshidratadas adheridas a laminas portaobjetostratadas con poli-lisina. Al determinar la dilucion de trabajo de 32 anticuerpos monoclonales y 3 policlonales, se observo que con la misma cantidad de estos reactivos se pueden realizar entre 5 y 100 veces mas determinaciones con respecto al metodo de inmunofluorescencia indirecta. Entre otras ventajas, este metodo permite realizar 21 determinaciones en una misma lamina portaobjeto, requiere una menor cantidad de celulas, los resultados se evaluan en un microscopio de luz visible y las colaboraciones no se desvanecen con el tiempo, lo que permite realizar estudios retrospectivos

Apoptose ou morte celular programada: um novo conceito em patologia? / Apoptosis or programmed cel death: a new concept in pathology?

A apoptose pode ser considerada como um tipo novo e fascinante de morte celular, e está envolvida em diversos fenômenos fisiológicos e patológicos. O objetivo da presente revisäo é atualizar os conceitos mais recentes de morte celular, sumariando-os e dando-se ênfase à apoptose e à sua diferenciaçäo com a necrose. O papel da apoptose na maturaçäo do sistema imunológico, seu desenvolvimento no desenvolvimento de auto-imunidade e de doenças imunossupressivas, assim como sua possível conexäo no processo de oncogênese recebem atençäo especial nesse enfoque.

Efecto de la gamaglobulina humana intravenosa sobre el cultivo mixto de linfocitos

Se estudio el efecto de la gamaglobulina humana intravenosa (GGHIV)(Sandoblogulin) sobre la reacción alogénica in vitro mediante el cultivo mixto de linfocitos (CML) en individuos normales. LA GGHIV en concentraciones superiores a 0.5 mg/ml inhibió en 61 por ciento y 99 por ciento la respuesta proliferativa. Se descartó que la inhibición fuese debida a factores citotóxicos presentes en la GGHIV comercial y/o deficit nutricional en los medios de cultivo. La incubación de los CML con 4 mg/ml de GGHIV durante 4 h/37 grados Centigrados produjo un 74 por ciento de inhibición. Se observó un efecto más acentuado al preincubar las células estimuladoras. La adición de GGHIV al CML, ocasionó una inhibición dependiente del tiempo de adición, mayor entre las 0 horas (h)(90 por ciento) y las 48 h (40 por ciento). El fenómeno inhibitorio no fue específico sobre la reacción alogénica puesto que también se encontró sobre la respuesta proliferativa a concavalina A (Con A) (63 por ciento), fitohematoglutinina A (PHA) (62 por ciento) y derivado protéico purificado (PPD) (84 por ciento). La inhibición sobre el CML, se revirtió parcialmente con la adición de 100 U de IL-2rH en las primeras 24h. La GGHIV redujo en un 79 por ciento la expresión del receptor de IL-2 al quinto día del CML. Los resultados de cuantificación de IL-1B en los sobrenadantes de CML con y sin GGHIV no arrojaron datos concluyentes. Se discuten los posibles mecanismos de acción y futuras utilidades de la GGHIV como inmunomoduladora en los transplantes de tejidos.