title: 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.
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, Medical School of the University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, Sao Paulo, Brazil.
authors.forename: Léia C R
authors.initials: LC
authors.lastname: Silva
authors.forename: Guilherme G
authors.initials: GG
authors.lastname: Silveira
authors.forename: Marcelo
authors.initials: M
authors.lastname: Arnone
authors.forename: Ricardo
authors.initials: R
authors.lastname: Romiti
authors.forename: Annemiek
authors.initials: A
authors.lastname: Geluk
authors.forename: Kees C L M
authors.initials: KC
authors.lastname: Franken
authors.forename: Alberto José da Silva
authors.initials: AJ
authors.lastname: Duarte
authors.forename: Maria Denise Fonseca
authors.initials: MD
authors.lastname: Takahashi
authors.forename: Gil
authors.initials: G
authors.lastname: Benard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D001938:Brazil; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007109:Immunity; D007211:Indoles / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D011565:Psoriasis / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007211:Indoles; D016753:Interleukin-10; C093656:AG 85; D007371:Interferon-gamma