RESUMEN

The cross-talk between the innate and adaptive immune response represents the first defense weapon against the threat of pathogens. Substantial evidence has shown a relationship between immune phenotype lymphocytes and COVID-19 disease severity and/or implication in susceptibility to SARS-CoV-2 infection. Recently, belonging to ABO blood groups has been investigated as a correlation factor to COVID-19 disease. This pilot study investigated lymphocyte typing in a cohort of blood donors to understand the underlying mechanism in SARS-CoV-2 infection linked to the blood group. The study cohort consisted of 20-64-year-old subjects, without comorbidities, from both sexes, who were COVID-19 vaccinated with previous or no infection history. Whole blood samples, collected at A.O.R.N. Sant'Anna and San Sebastiano Hospital (Campania Region), were processed by multiparametric cytofluorimetric assay, to characterize CD4+ helper and CD8+ cytotoxic T cell CD3+ subpopulations. The CD45RA, CCR7, CD27, CD28, CD57 and PD-1 markers were investigated to delineate the peripheral T-cell maturation stages. Differences were detected in ABO blood types in CD3+, CD4+ gated on CD3+, CD8+ and CD8+ gated on CD3+ percentage. These results contribute to identifying a memory cell "identikit" profile in COVID-19 disease, thus leading to a useful tool in precision medicine.

RESUMEN

Anticytoplasmic neutrophil antibodies (ANCA)-associated vasculitis (AAV) are rare systemic immune-mediated diseases characterized by small vessel necrotizing vasculitis and/or respiratory tract inflammation. Over the last 2 decades, anti-MPO vasculitis mouse model has enlightened the role of ANCA, neutrophils, complement activation, T helper cells (Th1, Th17) and microbial agents. In humans, CD4T cells have been extensively studied, while the dramatic efficacy of rituximab demonstrated the key role of B cells. Many areas of uncertainty remain, such as the driving force of GPA extra-vascular granulomatous inflammation and the relapse risk of anti-PR3 AAV pathogenesis. Animal models eventually led to identify complement activation as a promising therapeutic target. New investigation tools, which permit in depth immune profiling of human blood and tissues, may open a new era for the studying of AAV pathogenesis.

Asunto(s)

RESUMEN

@#Objective To investigate the effects of mercury on T lymphocytes and serum immune indexes of workers with Methods occupational mercury exposure. A total of 45 workers with occupational mercury exposure were selected as the ， mercury exposure group and 47 workers without occupational mercury exposure were selected as the control group using the judgment sampling method. Cold atomic absorption spectrometry was used to detect the urinary mercury level of the two groups. （ ） +， + +， + + - + Flow cytometry was used to detect the proportion of cluster of differentiation CD 3 CD3CD4 CD3CD8 and CD3CD19 ， - （ - ） - （ - ） cells in peripheral blood and the levels of tumor necrosis factor α TNF α and interleukin 8 IL 8 in serum. The levels of （ ） ， Results immunoglobulin Ig A IgG and IgM in serum were measured by immune nephelometry. The urinary mercury level of （ ： vs ，P ） individuals in the mercury exposed group was higher than that of the control group median 92.7 13.2 μg/g Cr <0.01 . The +， + +， - + proportion of CD3 CD3CD4 CD3CD19 cells in peripheral blood and serum IgG level in the mercury exposed group （ P ）， - - （ P ） decreased all <0.05 and the serum TNF α and IL 8 levels increased all <0.01 compared with the control group. Urinary - + mercury level was negatively correlated with the proportion of CD3CD19 cells in peripheral blood and serum IgG level in the ［ （r） ， ， P ］， study subjects Spearman correlation coefficient S were −0.21 and −0.31 respectively all <0.05 and positively - - （r ， ， P ） ， correlated with serum TNF α and IL 8 levels S were 0.36 and 0.39 respectively all <0.05 . However the urinary mercury （ P ）， +， + +， level was neither correlated with IgA and IgM levels in serum all >0.05 nor with the proportion of CD3 CD3CD4 + + （ P ） Conclusion CD3CD8 cells in peripheral blood all >0.05 . Occupational exposure to mercury can lead to abnormal ， changes in peripheral blood T lymphocyte subsets B lymphocytes and serum immune factors in workers. The mercury load of occupational mercury exposure workers may impact their immune function.

RESUMEN

Resumen El pénfigo vulgar es una enfermedad ampollar crónica de etiología autoinmune, en la cual el diagnóstico y tratamiento precoz disminuye la morbimortalidad de los pacientes. Actualmente se utilizan corticosteroides de primera línea asociados a inmunosupresores. Sin embargo,se ha visto que el uso de Rituximab como terapéutica de primera elección en los países desarrollados ha disminuido las reacciones adversas, con lo que mejora la calidad de vida de los pacientes. Se presentan cinco pacientes con diagnóstico de pénfigo vulgar refractario a tratamientos convencionalesque requirieron tratamiento con Rituximab.

Abstract Pemphigus vulgaris is an autoimmune chronic blistering disease. Its early diagnosis and treatment help reduce patient mortality and morbidity. Corticosteroids associated with immunosuppressants remain the standard treatment for pemphigus vulgaris. However, the use of Rituximab as first-line therapy in developed countries has been effective in reducing adverse effects improving the quality of life of patients. We report five patients with a diagnosis of pemphigus vulgaris refractory to conventional treatments requiring treatment with Rituximab.

RESUMEN

Sjögren's syndrome (SS) is a systemic autoimmune epithelitis with a major female incidence, and characterized by a dry syndrome, impaired quality of life, visceral involvement, and lymphoma for the most aggressive cases. During this process, epithelial cells acquire the capacity to produce cytokines, chemokines, and autoantigens which can in turn be presented to the immune system. Consequently, this epithelitis is accompanied by lymphocytic infiltrations leading to the formation of pseudo-follicles in which self-reactive B lymphocytes are present. The recent integration of genomic and especially of epigenomic data, which make it possible to analyze the different cellular partners, opens new perspectives and allows to a better understanding of this complex and still incurable disease.

Asunto(s)

RESUMEN

Waldenström's macroglobulinemia (WM) is a lymphoproliferative disease of B lymphocytes, characterized by a lymphoplasmocytic lymphoma in the bone marrow and by IgM monoclonal hypergammaglobulinemia. It was first described in 1944 by Jan Gösta Waldenström, reporting two patients with oronasal bleeding, lymphadenopathy, anemia, thrombocytopenia, high erythrocyte sedimentation rate and serum viscosity, normal radiography and bone marrow infiltrated by lymphoid cells. The WM is a rare disease with a typically indolent clinical course, affecting mainly individuals aged between 63 and 68 years. Most patients have clinical signs and symptoms related to hyperviscosity resulting from IgM monoclonal gammopathy, and/or cytopenias resulting from bone marrow infiltration by lymphoma. The differential diagnosis with other lymphomas is essential for the assessment of prognosis and therapeutic approach. Treatment of patients with asymptomatic WM does not improve the quality of life of patients, or increase their survival, being recommended, therefore, their follow-up. For the treatment of symptomatic patients, alkylating agents, purine analogs and anti-CD20 monoclonal antibodies are used. However, the disease is incurable and the response to therapy is not always favorable. Recent studies have shown promising results with bortezomib, an inhibitor of proteasomes, and some patients respond to thalidomide. In patients with relapse or refractory to therapy, autologous transplantation may be indicated. The aim of this paper is to describe in detail the current knowledge on the pathophysiology of WM, main clinical manifestations, diagnosis, prognosis and treatment.

A macroglobulinemia de Waldenström (MW) é uma doença linfoproliferativa dos linfócitos B, caracterizada por um linfoma linfoplasmocítico na medula óssea e por hipergamaglobulinemia monoclonal de tipo IgM. Foi descrita pela primeira vez em 1944, por Jan Gösta Waldenström, que descreveu dois doentes com hemorragia oronasal, adenopatias, anemia, trombocitopenia, velocidade de sedimentação eritrocitária e viscosidade sérica elevadas, radiografia óssea normal e medula óssea infiltrada por células linfoides. A MW é uma doença rara com um percurso clínico normalmente indolente, atingindo principalmente os indivíduos com idades entre 63 e 68 anos. A maioria dos doentes apresenta sintomas e manifestações clínicas relacionadas com a hiperviscosidade, resultante da gamopatia monoclonal IgM e/ou com as citopenias, resultantes da infiltração medular pelo linfoma. O diagnóstico diferencial com outros linfomas é essencial para a avaliação do prognóstico e a abordagem terapêutica. O tratamento dos doentes com MW assintomática não melhora a qualidade de vida do doente nem aumenta a sua sobrevivência, recomendando-se o acompanhamento clínico. Para o tratamento dos doentes sintomáticos, são usados agentes alquilantes, análogos das purinas e anticorpos monoclonais anti-CD20. No entanto, a doença é incurável e a resposta à terapêutica nem sempre é favorável. Estudos relativamente recentes mostram resultados promissores com o bortezomibe, um inibidor dos proteossomas, e alguns doentes respondem à talidomida. Nos doentes com recidivas ou refratários à terapêutica, pode-se indicar o transplante autólogo. O objetivo deste trabalho é descrever, de forma detalhada, o conhecimento atual sobre a fisiopatologia da MW, as principais manifestações clínicas, o diagnóstico, o prognóstico e o tratamento.

RESUMEN

Primary Sgögren's syndrome (SSP) is one of the most common connective tissue disorder with an estimated prevalence between 0.6 and 1.7% of the general population. Lymphocytic infiltration of salivary gland is easily accessible favoring the diagnosis, and clinical and fundamental research. However, while many advances have been obtained in the recent decades, the pathophysiology of SSP remains unclear combining environmental factors with genetic predisposition. A central role tends to be attributed to salivary gland epithelial cells, originally designated as "innocent bystanders" and to B cells through the intervention of survey factors like BAFF. New T cells subsets are also carefully studied, particularly natural T regulatory and Th17 cells. They could indeed represent new therapeutic targets.

Asunto(s)

RESUMEN

Introdução: A Imunodeficiência Comum Variável (ICV) faz parte de um grupo de imunodeficiências primárias na qual os pacientes apresentam defeitos na maturação e diferenciação dos linfócitos B (LB), resultando em distúrbios funcionais além de alterações na distribuição de seus subtipos. Consequentemente, estes pacientes apresentam hipogamaglobulinemia, susceptibilidade a infecções e ausência de produção de anticorpos a antígenos específicos. Na tentativa de reduzir os episódios de infecções recorrentes, alguns trabalhos têm recomendado a vacinação com patógenos mortos ou subunidades e em trabalho anterior demonstramos a eficácia clínica da vacinação de pacientes com ICV, porém, a experiência com a administração de vacinas em imunocomprometidos é limitada. Objetivos: Avaliar a cinética da distribuição das subpopulações de linfócitos B antes e após a vacinação com antígenos proteicos e polissacarídicos em pacientes com ICV acompanhados no Ambulatório de Imunodeficiências Primárias do Hospital das Clínicas, FMUSP, além da produção de anticorpos específicos aos antígenos vacinais. Pacientes e Métodos: Um grupo de 35 pacientes com ICV e 16 controles foram vacinados contra Influenza, H1N1 e S. pneumoniae. Após as coletas nos tempos pré e pós 1, 3 e 6 meses foram realizados a separação de PBMC e cultura de linfócitos com lisado viral e hemaglutinina de Influenza, além da citometria de fluxo para identificação das subpopulações de LB naive, zona marginal (MZB), memória com troca de isotipo (SMB) e plasmoblastos (PBL). Foram dosados os anticorpos específicos e no grupo dos pacientes foi aplicado um score de sintomas antes e após a imunização. Resultados: Apesar da redução significativa na pontuação do score de sintomas, a maioria dos pacientes não produziu anticorpos específicos para Influenza, H1N1 e S. pneumoniae...

Introduction: Common Variable Immunodeficiency (CVID) is a primary antibody deficiency characterized by defects in B lymphocyte maturation, resulting in disturbed differentiation, distribution and functional variations on its subtypes. As a result , CVID patients have hypogammaglobulinemia and poor antibody response to specific antigens with increased susceptibility to infections. In an effort to minimize the recurrent episodes of infections, some studies have recommended immunization with inactivated pathogens or subunits and in a former study we have shown the clinical improvement determined by immunization in CVID patients, but the experience with vaccines' administration to immunodeficient patients is limited. Objectives: To evaluate the changes in distribution of B cell subtypes before and after vaccination of CVID patients followed at the Division of Clinical Immunology and Allergy of University of São Paulo Medical School with protein and polysaccharide antigens, as well as specific antibody production . Methods: A group of 35 CVID patients and 16 controls were vaccinated against Influenza, H1N1 and S. pneumoniae vaccines. Blood samples were collected before and 1, 3 and 6 months post vaccination. PBMCs were stimulated with Influenza viral lysate and hemagglutinin peptide. Flow cytometry was performed to identify naïve B cells, marginal zone (MZB), switched memory B cells (SMB) and plasmablasts (PBL). Specific antibody production was measured and a symptoms score was applied for clinical evaluation before and after immunization. Results: In spite of the significant reduction in symptoms score after vaccination, most patients didn't produce specific antibodies to Influenza, H1N1 and S. pneumoniae...

Asunto(s)

RESUMEN

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). The appearance of demyelinating patches in the CNS of patients with MS is associated with an inflammatory infiltrate mainly composed of macrophages and T lymphocytes. In this review, we focus on the evidence linking the development of the disease and the cell populations of the adaptative immune system. This evidence arises from anatomopathological, genetical and immunological studies, both on human and the animal model of the disease. Hence, we detail the implication of the effector lymphocytes, i.e. CD4(+) and CD8(+) T lymphocytes, but also B lymphocytes, in the disease. The implication of the regulatory T and B lymphocytes is also approached. Finally, the main hypotheses proposing an explanation to the development of MS are presented.

Asunto(s)