Análise das subpopulaçoes linfocitárias na esclerose sistemica

Orientador: Acir RachidCo-orientadora: Mariester MalvezziTese (doutorado) - Universidade Federal do Paraná, Setor de Ciencias da SaúdeResumo: A Esclerose Sistemica (ES) e uma doenca inflamatoria cronica do tecido conjuntivo, de etiologia desconhecida, caracterizada por fibrose e dano microvascular dos orgaos afetados. Ha varias evidencias de que a ativacao do sistema imune celular participa de maneira expressiva na sua patogenese. O objetivo deste estudo foi analisar numericamente as subpopulacoes linfocitarias de pacientes com ES e sua possivel correlacao com fatores clinicos e laboratoriais. Foi estudado um grupo de 42 pacientes que preencheram os criterios de diagnostico do Colegio Americano de Reumatologia para ES e um grupo de 28 controles normais. Os pacientes foram selecionados no ambulatorio de Reumatologia do Hospital de Clinicas da Universidade Federal do Parana, no periodo de outubro de 1997 a setembro de 1999. Foram realizadas avaliacao clinica, capilaroscopia periungueal e pesquisa dos seguintes parametros imunes: anticorpo antinuclear, anti-Scl-70, anticentromero, anti-RNP, anti-Ro, anti-La, anti- Sm e antigenos linfocitarios CD2, CD3, CD4, CD8, CD19, CD25, CD45RA, CD56, CD71, HLA-DR, TCRa/p e TCRy/o. Ambos os grupos tiveram suas subpopulacoes linfocitarias avaliadas atraves da citometria de fluxo. Dos 42 pacientes, 38 (90,5%) eram do sexo feminino e 4 (9,5%) do sexo masculino. A idade por ocasiao do inicio da doenca variou de 11 a 54 anos, com media de 37,5 anos e o tempo de duracao da doenca variou de 1 a 30 anos, com media de 6,1 anos. Nos pacientes com ES comparados ao grupo controle foram encontrados valores percentuais normais para os linfocitos T CD2+, CD3+, CD3+CD4+, CD3+CD8+, CD25+, CD4+CD45RA+, CD8+CD45RA+, CD71+ e para a relacao CD4+/CD8+. Em contraste, os linfocitos T CD3+TCRy/o+ mostraram-se com percentuais diminuidos nos pacientes com ES difusa, de longa duracao, com envolvimento pulmonar caracterizado por doenca pulmonar restritiva, envolvimento muscular e presenca de anticorpo anti-Scl-70. Os pacientes com a forma difusa da ES apresentaram tanto na fase recente como na tardia aumento na percentagem de linfocitos T CD4+ e CD8+ expressando moleculas de ativacao HLA-DR. Na fase tardia da doenca, nao importando a forma clinica, foi encontrado aumento na percentagem de linfocitos T CD4+CD45RA+. Os pacientes com ES limitada e fase recente mostraram diminuicao na percentagem de linfocitos B CD19+. Os pacientes com doenca difusa e fase tardia apresentaram diminuicao na percentagem dos linfocitos NK CD56+. Estes resultados sugerem que as alteracoes dos linfocitos T, B e NK possam estar envolvidas no processo de desencadeamento e/ou perpetuacao da ES, podendo talvez, em alguns subgrupos particulares de pacientes, ter utilidade prognostica.Abstract: Systemic sclerosis (SSc) is a chronic inflammatory connective tissue disease, of unknown etiology, characterized by fibrosis and microvascular injury in affected organs. It has become clear that activated cellular immune system plays a central role in the pathogenesis of SSc. The purpose of this study was to analyze the lymphocyte sub-populations numbers and their correlations with clinical and laboratoryal manifestations. We studied a group of 42 patients who fulfilled the American College Rheumatism criteria for SSc and a group of 28 matched normal controls. The patients were followed at Rheumatology Unit of Hospital de Clinicas - Federal University of Parana - Brazil, from october 1997 to September 1999. Clinical involvement, nailfold capillaroscopy and immunologic parameters: antinuclear antibodies, anti-Scl-70 antibodies, anticentromeric antibodies, anti- RNP antibodies, anti-Ro antibodies, anti-La antibodies, anti-Sm antibodies and lymphocyte cell-surface markers CD2, CD3, CD4, CD8, CD19, CD25, CD45RA, CD56, CD71, HLA-DR, TCRa/p and TCRy/5 were analyzed. Both groups had lymphocyte sub-populations evaluated by flow cytometry. Among the 42 patients 38 (90,5%) were female, and 4 (9,5%) male, the age of disease onset ranged from 11 to 54 years (mean: 37,5 years) and the disease duration ranged from 1 to 30 years (mean: 6,1 years). Patients with SSc had similar percentages of CD2+, CD3+, CD3+CD4+, CD3+CD8+, CD25+, CD4+CD45RA+, CD8+CD45RA+, CD71+ cells and CD4+/CD8+ cells ratio whem compared to normal controls. In contrast, the TCRy/5 cells had significantly smaller percentages in SSc patients with diffuse and late-stage disease with pulmonary involvement (intersticial pulmonary changes), muscle involvement and anti-Scl-70 antibodies presence. Patients with early and late-stage disease and diffuse SSc had significantly increased percentages of HLA-DR in CD4+ and CD8+ T cells. Patients with latestage disease had increased percentages of CD4+CD45RA+ T cells. Patients with limited and early-stage disease had smaller percentages of B cells (CD19+). Patients with diffuse and late-stage disease had smaller percentages of NK cells (CD56+). These results suggest that T, B and NK cells alterations may be involved at the onset and/or perpetuation of the disease processes and may eventually be useful as a prognostic indicator in selected patient subgroups