{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T04:14:06Z","timestamp":1747196046887,"version":"3.40.5"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T00:00:00Z","timestamp":1627862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>This study was aimed at exploring whether latent tuberculosis infection (LTBI) contributes to the pathogenesis of immune-mediated inflammatory diseases in a TB endemic setting. We screened 198 rheumatoid arthritis (RA) patients with tuberculin skin test (TST) and studied 61 (median DAS28-ESR = 6.3) who were positive. Whole blood T cell proliferative responses to<jats:italic>Mycobacterium tuberculosis<\/jats:italic>(Mtb) membrane (MtM) antigens, including the latency-induced protein alpha crystallin (Acr), were determined by flow cytometry using Ki67 expression as the marker for nuclear proliferation. Serum antibody levels were determined by ELISA. Follow-up investigations (at 3\u20136, 9\u201312 and 15\u201318 months after baseline) were performed in 41 patients who were classified empirically as \u2018high\u2019 (HR-T\/HR-B) or \u2018low\u2019 (LR-T\/LR-B) responders based on their dynamic T cell or antibody responses. Significant correlations were seen between baseline T cell responses to MtM and Acr, and between IgG, IgA and IgM antibody responses to MtM. However, no correlation was seen between T and B cell responses. At all time points during the follow-up, T cell responses to both antigens (except for MtM at one point) were significantly higher in HR-T (n = 25) than LR-T (n = 16) patients. Levels of IgA and IgM (but not IgG) antibodies to MtM were also significantly higher in HR-B (n = 13) than LR-B (n = 28) at all time points. Importantly, HR-T patients exhibited significantly higher baseline and follow-up DAS28 scores than LR-T. Ten (of 61) patients had a history of TB and developed RA 6 years (median) after contracting TB. Three new TB cases (1 from TST-positive and 2 from TST-negative groups) emerged during the follow-up. Our results suggest that persistently elevated T cell responses to Mtb antigens may contribute to disease activity in RA.<\/jats:p>","DOI":"10.1371\/journal.pone.0255639","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T17:35:35Z","timestamp":1627925735000},"page":"e0255639","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Patterns of T and B cell responses to Mycobacterium tuberculosis membrane-associated antigens and their relationship with disease activity in rheumatoid arthritis patients with latent tuberculosis infection"],"prefix":"10.1371","volume":"16","author":[{"given":"Shashi Kant","family":"Kumar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suvrat","family":"Arya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ankita","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramnath","family":"Misra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amita","family":"Aggarwal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3149-1116","authenticated-orcid":true,"given":"Sudhir","family":"Sinha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,8,2]]},"reference":[{"key":"pone.0255639.ref001","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"JS Smolen","year":"2016","journal-title":"Lancet"},{"key":"pone.0255639.ref002","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1136\/annrheumdis-2020-217092","article-title":"Infectious complications of rheumatoid arthritis and psoriatic arthritis during targeted and biological therapies: a viewpoint in 2020","volume":"79","author":"O Lortholary","year":"2020","journal-title":"Ann Rheum Dis"},{"journal-title":"Latent TB infection: updated and consolidated guidelines for programmatic management","year":"2018","author":"World Health Organization","key":"pone.0255639.ref003"},{"key":"pone.0255639.ref004","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.jbspin.2010.12.004","article-title":"Incidence of tuberculosis in patients with rheumatoid arthritis. 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