Infliximab partially impairs the anti-Mycobacterium tuberculosis immune responses of severe psoriasis patients with positive tuberculin skin-test

Autor(es)

Silva, L. C. R. ^[1] ; Geluk, A. ^[2] ; Arnone, M. ^[3] ; Romiti, R. ^[3] ; Franken, K. C. L. M. ^[2] ; Duarte, A. J. S. ^[1] ; Takahashi, M. D. F. ^[3] ; Benard, G. ^{[1, 4]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Lab Dermatol & Immunodeficiencies, Sao Paulo - Brazil

^[2] Leiden Univ, Dept Infect Dis, Med Ctr, Leiden - Netherlands

^[3] Univ Sao Paulo, Sch Med, Hosp Clin, Div Clin Dermatol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Trop Med, Lab Med Mycol LIM 53, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY; v. 26, n. 3, p. 319-324, MAR 2012.
• Citações Web of Science: 2

Resumo

Background Infliximab and etarnecept are now widely used for treating severe psoriasis. However, these drugs, especially infliximab, increased the risk of tuberculosis reactivation. Surprisingly, epidemiological data suggest that the tuberculosis rate in patients taking infliximab in Sao Paulo State, Brazil, is similar to that of some developed, non-endemic countries. Objective The aim of this study was to better understand the effect of infliximab on Mycobacterium tuberculosis (Mtb) immune responses of psoriasis patients in an endemic setting (Brazil). Methods We evaluated the tuberculosis-specific immune responses of severe psoriasis patients and healthy individuals, both tuberculin skin test (TST) positive, in the presence/absence of infliximab. Patients had untreated severe psoriasis, no co-morbidities affecting the immune responses and a TST >10 mm. Healthy TST+ (>10 mm) individuals were evaluated in parallel. PBMC cultures from both groups were stimulated with different Mycobacterium tuberculosis (Mtb) antigens (ESAT-6, 85B and Mtb lysate) and phytohemagglutinin, with or without infliximab (5 mu g/mL). Parameters evaluated were TNF-alpha, IFN-gamma and IL-10 secretion by ELISA, overnight IFN-gamma ELISpot and lymphocyte proliferative response (LPR). Results Infliximab almost abolished TNF-alpha detection in PBMC supernatants of both groups. It also significantly reduced the LPR to phytohemagglutinin and the Mtb antigens as well as the IFN-gamma levels secreted into day 5 supernatants in both groups. There was no concomitant exaggerated IL-10 secretion that could account for the decreases in these responses. ELISpot showed that, contrasting with the central-memory responses above, infliximab did not affect effector-memory INF-gamma-releasing T-cell numbers. Conclusions Infliximab affected some, but not all aspects of the in vitro antituberculosis immune responses tested. The preserved effector-memory responses, putatively related to exposure to environmental mycobacteria, may help to explain the lower than expected susceptibility to tuberculosis reactivation in our setting. Received: 29 December 2010; Accepted: 9 March 2011 (AU)

• Processo FAPESP: 05/57761-7 - Avaliação do efeito do bloqueio de fator de necrose tumoral-a (TNF alfa) na resposta imune anti-Mycobacterium tuberculosis in vitro em pacientes com psoríase moderada a grave
• Beneficiário: Léia Cristina Rodrigues da Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 05/60075-8 - Avaliacao do efeito do bloqueio de fator de necrose tumoral-alfa (tnf-alfa) na resposta imune anti-mycobacterium tuberculosis in vitro em pacientes com psoriase moderada a grave.
• Beneficiário: Gil Benard
• Modalidade de apoio: Auxílio à Pesquisa - Regular