Epidemiological, clinical and immune factors that influence the persistence of antiphospholipid antibodies in leprosy

Abstract Introduction: Antiphospholipid antibodies (aPL) are described in individuals with leprosy without the clinical features of antiphospholipid antibody syndrome (APS), a condition involving thromboembolic phenomena. We have described the persistence of these antibodies for over 5 years in patients with leprosy after specific treatment. Objectives: To determine whether epidemiological, clinical and immunological factors played a role in the longterm persistence of aPL antibodies in leprosy patients after multidrug therapy (MDT) had finished. Methods: The study sample consisted of 38 patients with a diagnosis of leprosy being followed up at the Dermatology and Venereology Outpatient Department at the Alfredo da Matta Foundation (FUAM) in Manaus, AM. ELISA was used to detect anticardiolipin (aCL) and anti-β2 glycoprotein I (anti-β2GPI) antibodies. Patients were reassessed on average of 5 years after specific treatment for the disease (MDT) had been completed. Results: Persistence of aPL antibodies among the 38 leprosy patients was 84% (32/38), and all had the IgM isotype. Mean age was 48.1 ± 15.9 years, and 23 (72.0%) were male. The lepromatous form (LL) of leprosy was the most common (n = 16, 50%). Reactional episodes were observed in three patients (9.4%). Eighteen (47.37%) were still taking medication (prednisone and/or thalidomide). Mean IgM levels were 64 U/mL for aCL and 62 U/mL for anti-β2GPI. In the multivariate binary logistic regression the following variables showed a significant association: age (p = 0.045, OR = 0.91 and CI 95% 0.82-0.98), LL clinical presention (p = 0.034; OR = 0.02 and CI 95% = 0.0-0.76) and bacterial index (p = 0.044; OR = 2.74 and CI 95% = 1.03-7.33). We did not find association between prednisone or thalidomide doses and positivity for aPL (p = 0.504 and p = 0.670, respectively). No differences in the variables vascular thrombosis, pregnancy morbidity, diabetes, smoking and alcoholism were found between aPL-positive and aPL-negative patients. Conclusion: Persistence of positivity for aPL antibodies was influenced by age, clinical presentation and bacterial index. However, further studies are needed to elucidate the reason for this persistence, the role played by aPL antibodies in the disease and the B cell lineages responsible for generation of these antibodies.

Oral manifestations and histopathology of minor salivary gland from patients with Sjögren's Syndrome and its diagnosis in a public health system

Objective: to analyze the oral manifestations, sialometry and the histopathology of the minor salivary glands of patients with Sjögren Syndrome (SS) treated in a public health system and diagnosed according to European American Consensus Group (EACG) criteria. Material and Methods: the 32 patients were submitted to Shirmer test, oral cavity exam, unstimulated and stimulated salivary flow measurement and, in some cases, to the serological testing. For certain patients a minor salivary gland biopsy was carried out. Results: 10 patients were diagnosed with Sjögren Syndrome (SS), among whom: 40% were diagnosed with primary (pSS) and 60% with secondary Sjögren Syndrome (sSS). All patients diagnosed with this condition complained of xerostomia and xeropthalmia. Besides xerostomia, the most frequent oral manifestations were difficulty in swallowing, dry lips, hyperemic gums and atrophic change in tongue papillae. The average scores of the Schirmer and salivary flow tests were lower in patients with sSS. Conclusion: the oral signs and symptoms are extremely important in the multisystem involvement of the SS, which emphasizes the dental surgeon responsibility in managing these patients. The establishment of multidisciplinary diagnostic centers is of utmost importance, as well as the ability to offer more objective exams in the public health system aiming at increasing the accuracy of Sjögren Syndrome diagnosis.

The effects of brief physical conditioning on immune cells and cytokines in elderly individuals in Manaus, Amazonas / Efeito do condicionamento físico breve em células imunes e citocinas em idosos na cidade de Manaus, Amazonas

Abstract Introduction: Aging is understood as the sum of all biological, psychological and social changes that occur over the years. Associated with aging we list up the changes of morphological and functional order of the immune system: Immunosenescence. Objective This study's objective was to characterize the effect of a brief exercise program on the profile of cytokines and peripheral blood mononuclear cells of elderly individuals in Manaus, AM, Brazil. Materials and methods: Twelve subjects aged 66.8 (± 3.7) years old on average engaged in three weekly sessions of exercises for 16 weeks and, seven subjects aged 66.1 (± 6.7) years on average, who practiced only recreational activities, composed the control group. Serum levels of IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and INF-γ were measured using the CBA technique (cytometric Bead Array) and the count of subpopulations of lymphocytes - B, B1, T/CD4, T/CD8, Treg, NK and NKT - was performed using flow cytometry. Results: The relative number of B lymphocytes, T/CD4+ and NKT (CD3+/CD16 +/CD56+) increased significantly (p <0.05) after physical activity, compared to the pre-exercise phase and the control group. In another analysis, each individual in the test group was classified either as major or minor producer of each cytokine; i.e., their values were above or below the cut-off point defined by the median of all measurements of that cytokine. Patterns of cytokine production were observed in the post-exercise group, which allowed defining sets ("signatures") of cytokines that were associated with the practice of short-term physical exercises. Conclusion: Our work showed that exercise induces changes in the count of immune cells, which allows us to infer that it can be used as an alternative to reverse or mitigate the implications of immunosenescence.

Resumo Introdução: O envelhecimento é compreendido como a soma de todas as alterações biológicas, psicológicas e sociais que ocorrem com o passar dos anos. Associadas ao envelhecimento elencam-se as alterações de ordem morfológica e funcional do sistema imunológico: Imunossenescência. Objetivo: Caracterizar o efeito do condicionamento físico breve sobre o perfil de citocinas e células mononucleares do sangue periférico de idosos na cidade de Manaus, AM. Materiais e métodos: Doze indivíduos com idade média de 66,8±3,7 anos realizaram 3 sessões semanais de exercícios físicos por 16 semanas e sete indivíduos com idade média de 66,1±6,7 anos, praticantes de atividades lúdicas, formaram um grupo controle. Os níveis séricos de IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α e INF-γ foram medidos pela técnica CBA (Cytometric Bead Array) e as contagens de subpopulações de linfócitos B, B1, T/CD4, T/CD8, TReg, NK e NKT foram realizadas por citometria de fluxo. Resultados: Observou-se que, após a atividade física, houve aumento significativo (p < 0,05) no número de linfócitos B, T/CD4 + e NKT (CD3 + /CD16 + /CD56 + ), quando comparados à fase pré-treinamento e ao grupo controle. Em outro modelo de análise, qualificando-se cada indivíduo do grupo teste como alto produtor ou baixo produtor das citocinas, observaram-se padrões na fase pós-treinamento que permitiram definir conjuntos ("assinaturas") de citocinas que se expressam associadas ao exercício. Conclusão: Nosso trabalho evidenciou que o exercício induz alterações na contagem de células imunes, o que nos permite inferir que pode ser usado como alternativa para reverter ou atenuar as implicações da imunossenescência.

Criptococose disseminada em lúpus eritematoso sistêmico juvenil / Disseminated cryptococcosis in juvenile systemic erythematosus lupus

O lúpus eritematoso sistêmico (LES) é uma doença inflamatória multissistêmica, na qual as infecções são responsáveis por altos índices de morbimortalidade. Os usos de corticóide e imunossupressores contribuem para o aumento das infecções. Embora as bactérias sejam os agentes mais comuns, grande variedade de patógenos tem sido relatada. Este artigo descreve um caso de LES em um menino de 15 anos com criptococose disseminada (sistema nervoso central, pulmão e rim) e encefalite tuberculosa presumível. A coexistência de infecção por Cryptococcus e LES é descrita na literatura, mas a associação desta com encefalite tuberculosa é incomum. O risco potencial de infecções em pacientes lúpicos imunossuprimidos deve alertar o médico a adotar estratégias diagnósticas e terapêuticas precoces visando ao espectro ampliado de possíveis patógenos.

Systemic lupus erythematosus (SLE) is a multisystem inflammatory disease, in which infection is responsible for high rates of mortality. The use of corticosteroids and immunosuppressive therapy contributes to this high incidence of infections. Although bacteria are the most common agents, a wide variety of pathogens has been reported. This article reports a case of SLE in a 15 years-old boy with disseminated criptococosis (central nervous system, lungs and kidneys) and presumptive tuberculous encephalitis. The coexistence of infection by Cryptococcus and SLE is described in the literature, but the combination of this with tuberculous encephalitis is uncommon. The potential risk of infection in immunosuppressed SLE patients should alert the physician to adopt early diagnostic and therapeutic strategies aiming at an extended spectrum of pathogens.

Síndrome de Felty: relato de caso e revisão da terapêutica / Felty's syndrome: case report and review of therapeutics

Os autores relatam um caso de artrite reumatóide, com 20 anos de evolução, que desenvolveu neutropenia e esplenomegalia em uso de 20 mg de metotrexato, que persistiu mesmo com sua substituição pela ciclosporina A. Apresentou infecções de orofaringe, pele e trato urinário. Após afastar doenças hematológicas, o diagnóstico foi de síndrome de Felty. Realizou-se o tratamento com antibioticoterapia, fator estimulador de colônia de granulócitos e macrófagos, pulsoterapia com metilprednisolona e leflunomida. Evoluiu inicialmente com melhora clínica e laboratorial. Após 2 meses de uso do leflunomida, foi admitida em pronto-socorro com quadro de sepse, ocorrendo o óbito em poucas horas.

The authors describe the case of a 42 years-old female patient with rheumatoid arthritis with a 20 years of follow-up. The patient was using methotrexate (20 mg/week); she developed neutropenia and splenomegaly that persisted despite changing medication for cyclosporine A. She then developed oropharyngeal, skin and urinary tract infections. After excluding for hematological affections, she was diagnosed as presenting Felty's syndrome. She was started on antibiotics while receiving also granulocyte-macrophage colony stimulating factor, pulsed methylprednisolone, and leflunomide. Two moths after the initiation of leflunomide, she was admitted to an emergency hospital unit with septic shock that resulted in her death in a few hours.

Great expectations: SLE and the Human Genome Project

O lúpus eritematoso sistêmico é uma doença tipicamente multigênica e multifatorial, com grande complexidade clínica e fisiopatológica. O Projeto Genoma Humano constitui um passo decisivo para decifrar seus enigmas. Nos últimos 50 anos foi reconhecida uma série de disfunções no sistema imune de pacientes lúpicos, incluindo alterações em células B CD5* produtoras de anticorpos antinucleares naturais; em linfócitos T com deficiências de sinalização (cadeia do receptor CD3, CD40-ligand); em diversas fases da apoptose (indução do processo e catabolismo dos fragmentos nucleares); nos perfis de produçao de citocinas com desvio TH2; sem falar na importante participação do sexo e do meio ambiente no determinismo da doença. Estima-se que cerca de 100 genes possam participar em sua patogenia, mas que apenas 10 ou 20 deles atuem em pacientes individuais. A construção de um modelo fisiopatológico em que esses mecanismos possam ser integrados é uma necessidade premente, que ajudará a visualizar que genes podem participar em cada uma das etapas biológicas que conduzem ao lúpus eritematoso sistêmico

Apoptosis and SLE: another piece in the puzzle

Recentes estudos apontam a apoptose - morte celular programada, organizada, necessária - como possível elemento participante da patogenia de lúpus eritematoso sistêmico e de outras doenças auto-imunes. Trabalhos iniciais demonstraram que camundongos com anomalia nos genes Fas e BCL-2 desenvolvem distúrbios auto-imunes, correspondentes na espécie humana à síndrome de Canale-Smith. No LES, pelo contrário, a funçäo Fas/BCL-2 é normal e observa-se aumento da taxa de células apoptóticas, em linhagens linfocíticas, monocíticas e queratinócitos. O interesse na relaçäo LES/apoptose cresce com a importante observaçÝo de que corpúsculo apoptóticos expressam antígenos nucleares - Ro, La, RNP, DNA, Sm, Ku, PARP - em sua membrana externa. Em doenças com aumento de apoptose, como a malária, observa-se aumento dos níveis dos anticorpos antinucleares. O autor discute a hipótese de que o aumento da oferta de antígenos nucleares, ligada à apoptose, poderia ser, no LES, fator determinante de mutaçäo somática, mudança de isotipo e refinamento de afinidade nos anticorpos antinucleares naturais, de linhagem germinativa. Maior conhecimento em questäo como essas certamente ajudaräo a desvendar a etiopatogenia do LES e doenças auto-imunes correlatas