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

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 São Paulo Stat...

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Published in:Journal of the European Academy of Dermatology and Venereology 2012-03, Vol.26 (3), p.319-324
Main Authors: Silva, L.C.R., Geluk, A., Arnone, M., Romiti, R., Franken, K.C.L.M., Duarte, A.J.S., Takahashi, M.D.F., Benard, G.
Format: Article
Language:English
Subjects:
Adult
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - therapeutic use
Data processing
Enzyme-Linked Immunosorbent Assay
Enzyme-Linked Immunospot Assay
ESAT-6 antigen
Female
gamma -Interferon
Humans
Immune response
Immunosuppressive agents
Infliximab
Interferon-gamma - blood
Interleukin 10
Interleukin-10 - blood
Lymphocytes
Lymphocytes T
Male
Monoclonal antibodies
Mycobacterium tuberculosis
Mycobacterium tuberculosis - immunology
Peripheral blood mononuclear cells
phytohemagglutinins
Psoriasis
Psoriasis - drug therapy
Psoriasis - immunology
Skin tests
Statistics, Nonparametric
Tuberculin
Tuberculin Test
Tuberculosis
Tumor necrosis factor- alpha
Tumor Necrosis Factor-alpha - blood
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Summary: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 São 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 μg/mL). Parameters evaluated were TNF‐α, IFN‐γ and IL‐10 secretion by ELISA, overnight IFN‐γ ELISpot and lymphocyte proliferative response (LPR). Results  Infliximab almost abolished TNF‐α detection in PBMC supernatants of both groups. It also significantly reduced the LPR to phytohemagglutinin and the Mtb antigens as well as the IFN‐γ 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‐γ‐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.
ISSN:0926-9959
1468-3083
DOI:10.1111/j.1468-3083.2011.04067.x