title: Infliximab partially impairs the anti-Mycobacterium tuberculosis immune responses of severe psoriasis patients with positive tuberculin skin-test.
abstract: 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.
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, Medical School of the University of São Paulo, São Paulo, Brazil.
authors.forename: L C R
authors.initials: LC
authors.lastname: Silva
authors.forename: A
authors.initials: A
authors.lastname: Geluk
authors.forename: M
authors.initials: M
authors.lastname: Arnone
authors.forename: R
authors.initials: R
authors.lastname: Romiti
authors.forename: K C L M
authors.initials: KC
authors.lastname: Franken
authors.forename: A J S
authors.initials: AJ
authors.lastname: Duarte
authors.forename: M D F
authors.initials: MD
authors.lastname: Takahashi
authors.forename: G
authors.initials: G
authors.lastname: Benard
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D000069285:Infliximab; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D018709:Statistics, Nonparametric; D014374:Tuberculin Test; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D000069285:Infliximab