{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:56:07Z","timestamp":1790787367185,"version":"4.1.0"},"reference-count":43,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T00:00:00Z","timestamp":1705449600000},"content-version":"unspecified","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Clinical Research Plan of Shanghai Hospital Development Center","award":["SHDC2020CR1015B"],"award-info":[{"award-number":["SHDC2020CR1015B"]}]},{"name":"Rheumatology special research project of Jiading District Central Hospital","award":["2021-JZXZDZK-01"],"award-info":[{"award-number":["2021-JZXZDZK-01"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2024,1,5]]},"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Indeterminate readout of the quantitative interferon-\u03b3 release test (QFT) for <jats:italic>Mycobacterium tuberculosis<\/jats:italic> screening is a specific laboratory finding for systemic lupus erythematosus (SLE), which may be due to T-cell exhaustion and abnormal programmed death receptor 1 (PD-1)\/programmed death-ligand 1 (PD-L1) signalling.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We enrolled 104 patients with SLE and 225 with other rheumatic musculoskeletal diseases (RMDs) who presented to the outpatient clinic between 2020 and 2023. Twenty healthy donors served as the controls. The QFT was performed in all participants, and those with indeterminate results were compared among the groups. Immunophenotyping and functional assays were performed using blood mononuclear cells. Interferon (IFN)-\u03b3 was detected in vitro and ex vivo in patients with SLE with indeterminate or negative QFT results, before or after rituximab therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>104 patients with SLE had a significantly higher rate of indeterminate QFT results was significantly higher (17.31%) than that of 225 patients with RMD (3.56%). Patients with SLE with indeterminate QFT had more active disease (SLEDAI-2K, mean 10.94 vs 4.02, p&lt;0.0001), including a higher incidence of active nephritis (55.56% vs 29.07%). Indeterminate QFT in SLE is mainly caused by an insufficient IFN-\u03b3 response in CD8+T cells with exhausted immunophenotypes. The abnormal interaction between exhausted PD-1 high CD8<jats:sup>+<\/jats:sup> T cells and activated PD-L1 low memory B cells in SLE can be reversed with a PD-1 agonist or increased PD-L1 expression. Rituximab treatment indirectly reversed this IFN-\u03b3 response.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The PD-1\/PD-L1 signalling pathway, which governs the crosstalk between exhausted CD8<jats:sup>+<\/jats:sup> T cells and activated memory B cells, is a mechanistic explanation for insufficient interferon-\u03b3 response in patients with SLE.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2023-003503","type":"journal-article","created":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T08:25:14Z","timestamp":1705479914000},"page":"e003503","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["PD-1\/PD-L1 governed cross-talk of exhausted CD8<sup>+<\/sup> T and memory B cells in systemic lupus erythematosus"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4943-9327","authenticated-orcid":false,"given":"Kaiwen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"},{"name":"Laboratory of Rheumatology & Immunology, Jiading Branch, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangfeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory of Rheumatology & Immunology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Clinical laboratory, Tibetan Medicine Hospital of Qinghai Province, Qinghai University School of Medicine, Xining, Qinghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangjun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Emergency, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2570-4576","authenticated-orcid":false,"given":"Fangfang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangling","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiting","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Rheumatology & Immunology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaer","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liou","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,1,17]]},"reference":[{"key":"2025090312042705000_10.1.e003503.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2016.186"},{"key":"2025090312042705000_10.1.e003503.2","doi-asserted-by":"publisher","DOI":"10.1191\/0961203306lu2289xx"},{"key":"2025090312042705000_10.1.e003503.3","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s10067-018-4303-z","article-title":"Active tuberculosis in patients with systemic lupus erythematosus from Southern China: a retrospective study","volume":"38","author":"Lao","year":"2019","journal-title":"Clin Rheumatol"},{"key":"2025090312042705000_10.1.e003503.4","unstructured":"Qiagen . 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