Decrease in Mycobacterium tuberculosis specific immune responses in patients with untreated psoriasis living in a tuberculosis endemic area

Abstract

Tuberculosis has emerged as a major concern in patients with immuno-mediated diseases, including psoriasis, undergoing treatment with biologicals. However, it is not known whether the chronically activated immune system of psoriasis patients interferes with their Mycobacterium tuberculosis (Mtb)-specific immunity, especially in tuberculosis-endemic areas like Brazil. We evaluated T-cell responses to a Mtb lysate and to the recombinant Mtb proteins ESAT-6 and Ag85B of tuberculin skin test (TST) positive and TST negative patients with severe or mild/moderate, untreated psoriasis in three different assays: lymphocyte proliferation, enzyme immunoassay for interferon (IFN)-gamma and interleukin (IL)-10 production by peripheral blood mononuclear cells and overnight enzyme immunospot (ELISpot) for enumerating IFN-gamma-secreting cells. In our cohort, a low proportion (29%) of the severe psoriasis patients tested were TST-positive. IFN-gamma and IL-10 secretion and T-cell proliferation to Mtb antigens were reduced in TST-negative but not in TST-positive patients with severe psoriasis when compared to healthy controls with the same TST status. Similarly, severe psoriasis patients had decreased cytokine secretion and proliferative response to phytohemagglutinin. However, most psoriasis patients and healthy controls showed detectable numbers of IFN-gamma-secreting effector-memory T-cells in response to Mtb antigens by ELISpot. TST-negative, mild/moderate psoriasis patients had responses that were mostly intermediary between TST-negative controls and severe psoriasis patients. Thus, patients with severe psoriasis possess decreased anti-Mtb central memory T-cell responses, which may lead to false-negative results in the diagnosis of TB infection, but retain T-cell memory-effector activity against Mtb antigens. We hypothesize that the latter may confer some protection against tuberculosis reactivation.

Association between traditional systemic antipsoriatic drugs and tuberculosis risk in patients with psoriasis with or without psoriatic arthritis: Results of a nationwide cohort study from Taiwan

“…33 These results suggested that aberrant T-cell response to M tuberculosis antigen in severe psoriasis may lead to reactivation of latent TB. Long-term use of systemic immunosuppressive drugs may partly explain the association between TB and psoriasis.…”

Infliximab Does Not Lead to Reduction in the Interferon-gamma and Lymphoproliferative Responses of Patients with Moderate to Severe Psoriasis

“…PBMC were stimulated with the mitogen phytohaemagglutinin (PHA), the superantigen enterotoxin B (SEB), from Staphylococcus aureus, a cytomegalovirus (CMV) lysate, and M. tuberculosis (Mtb) antigens, and the lymphocyte aetivation was evaluated by enzyme-linked immunosorbent spot assay (ELISpot) for enumeration of IFN-y-secreting cells, enzyme-linked immunoassay (ELISA) for detection of seereted IFN-y, and by [^H] thymidine incorporation for lymphocyte proliferation measurement. These assays were selected as in previous studies (12) because the ELISpot deteets T cells that, after a few hours (overnight) exposure to antigens or other stimuli, secrete IFN-y, a feature of effector memory T eells, while the IFN-y ELISA and lymphocyte proliferation assay preferentially measure functions of central memory T eells, which need several days after activation to undergo clonal expansion or secrete large amounts of cytokines.…”

Investigação de infecção tuberculosa latente em pacientes com psoríase candidatos ao uso de drogas imunobiológicas

“…TNF participation in the pathogenesis of psoriasis and stabilization of the granuloma in tuberculosis supports the hypothesis that anti-TNF therapy promotes reactivation of LTBI. 18 Between 1998 and 2002, the Adverse Event Reporting System of the FDA found 716 granulomatous infections associated with anti-TNF therapies, including tuberculosis, histoplasmosis, aspergillosis, listeriosis and cryptococcosis. Patients who developed tuberculosis during the anti-TNF therapy presented inability to form a granuloma, prominent interstitial fibrosis and lymph node inflammation.…”

“…When the memory function of T cells was tested, by means of a study in vitro via measuring the production of INF-γ, a decrease in this response was also observed, suggesting a characteristic similar to that presented by patients with rheumatoid arthritis. 18 The anti-M. tuberculosis reaction in these individuals is probably affected, especially if the housing area is endemic for infection with this bacillus. Therefore, one can expect that there is a higher incidence of false negative results for the PPD test in these patients compared with the population not affected by the disease, further distancing this test from being recognized as the gold standard in diagnosing latent tuberculosis.…”