{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T17:39:59Z","timestamp":1773337199945,"version":"3.50.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To elucidate the prognosis of patients with primary Sj\u00f6gren\u2019s syndrome (pSS) accompanied by hypergammaglobulinemia (HG), with a particular focus on the impact of various treatments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients were divided into the HG group and the non-HG group, based on the presence or absence of HG [serum immunoglobulin G (IgG) level above 16 g\/L]. The demographics, clinical manifestations, laboratory findings, medications and outcomes were compared between the two groups. The adverse outcome was defined as death or the increase of Sj\u00f6gren\u2019s Syndrome Disease Damage Index (SSDDI) score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>366 patients were included, with 225 (61.5%) in the non-HG group and 141 (38.5%) in the HG group. Compared with the non-HG group, the HG group had a greater proportion of females, higher disease activity, higher frequencies of organ involvements (excluding interstitial lung disease), and higher rates of autoantibody positivity, hypocomplementemia, and elevated erythrocyte sedimentation rate. After a follow-up of 36 (28-45) months, adverse outcomes were observed in 14 of 141 (9.9%) patients in the HG group and 23 of 225 (10.2%) in the non-HG group. In the Kaplan-Meier curve analysis, the risk of adverse outcomes did not differ between the two groups either unadjusted or corrected for conditions such as disease activity. However, compared with non-HG group, the HG group had a lower risk of poor prognosis when using immunosuppressive agents (ISA), and a trend toward a higher risk of poor prognosis when not using (adjusted P for interaction = 0.01).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Although the prognosis of pSS patients with HG was comparable to that of non-HG patients in this study, the application of ISA may help to improve the outcome of such patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1772604","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:48:09Z","timestamp":1773298089000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic benefit of immunosuppressive agents in primary Sj\u00f6gren\u2019s syndrome patients with hypergammaglobulinemia"],"prefix":"10.3389","volume":"17","author":[{"given":"Liupan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, Jiangsu, China"]},{"name":"Department of Critical Care Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiwen","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuoyang","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingfeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuebing","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1111\/j.1365-2249.2012.04587.x","article-title":"Cytokine\/chemokine profiles contribute to understanding the pathogenesis and diagnosis of primary Sjogren\u2019s syndrome","volume":"169","author":"Moriyama","year":"2012","journal-title":"Clin Exp Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2018.1","article-title":"B cells in the pathogenesis of primary Sjogren syndrome","volume":"14","author":"Nocturne","year":"2018","journal-title":"Nat Rev Rheumatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.55563\/clinexprheumatol\/volsh1","article-title":"Hypergammaglobulinaemia predicts glandular and extra-glandular damage in primary Sjogren\u2019s syndrome: results from the KISS cohort study","author":"Koh","year":"2021","journal-title":"Clin Exp Rheumatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-011-9553-3","article-title":"Active immunological profile is associated with systemic Sjogren\u2019s syndrome","volume":"31","author":"Martel","year":"2011","journal-title":"J Clin Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.13464","article-title":"Ten-year observation of patients with primary Sjogren\u2019s syndrome: Initial presenting characteristics and the associated outcomes","volume":"22","author":"Tsukamoto","year":"2019","journal-title":"Int J Rheum Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.13070","article-title":"Is extra-glandular organ damage in primary Sjogren\u2019s syndrome related to the presence of systemic auto-antibodies and\/or hypergammaglobulinemia? A long-term cohort study with 110 patients from the Netherlands","volume":"20","author":"Ter Borg","year":"2017","journal-title":"Int J Rheum Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2010.05.004","article-title":"Immunological profile in primary Sjogren syndrome: clinical significance, prognosis and long-term evolution to other auto-immune disease","volume":"9","author":"Fauchais","year":"2010","journal-title":"Autoimmun Rev"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/acr.23264","article-title":"Natural history and predictors of progression to Sjogren\u2019s syndrome among participants of the Sjogren\u2019s international collaborative clinical alliance registry","volume":"70","author":"Shiboski","year":"2018","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/mr\/road010","article-title":"Hyperglobulinemia predicts increased risk of mortality in primary Sjogren\u2019s syndrome: based on a Chinese multicentre registry","volume":"34","author":"Zhong","year":"2023","journal-title":"Mod Rheumatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket427","article-title":"Primary Sjogren\u2019s syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients","volume":"53","author":"Baldini","year":"2014","journal-title":"Rheumatol (Oxford)"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-007-8001-x","article-title":"Clinical, immunologic, and molecular factors predicting lymphoma development in Sjogren\u2019s syndrome patients","volume":"32","author":"Voulgarelis","year":"2007","journal-title":"Clin Rev Allergy Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1136\/ard.61.6.554","article-title":"Classification criteria for Sjogren\u2019s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group","volume":"61","author":"Vitali","year":"2002","journal-title":"Ann Rheum Dis"},{"key":"B13","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1136\/annrheumdis-2016-210571","article-title":"2016 American College of Rheumatology\/European League Against Rheumatism classification criteria for primary Sjogren\u2019s syndrome: A consensus and data-driven methodology involving three international patient cohorts","volume":"76","author":"Shiboski","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-208504","article-title":"Development of the ClinESSDAI: a clinical score without biological domain","volume":"75","author":"Seror","year":"2016","journal-title":"A tool Biol Stud Ann Rheum Dis"},{"key":"B15","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.jaut.2012.01.013","article-title":"Outcome measures for primary Sjogren\u2019s syndrome","volume":"39","author":"Seror","year":"2012","journal-title":"J Autoimmun"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/art.22658","article-title":"Sjogren\u2019s Syndrome Disease Damage Index and disease activity index: scoring systems for the assessment of disease damage and disease activity in Sjogren\u2019s syndrome, derived from an analysis of a cohort of Italian patients","volume":"56","author":"Vitali","year":"2007","journal-title":"Arthritis Rheum"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2003.10.004","article-title":"Adjusted survival curves with inverse probability weights","volume":"75","author":"Cole","year":"2004","journal-title":"Comput Methods Programs BioMed"},{"key":"B18","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1038\/nrneph.2015.174","article-title":"Renal involvement in primary Sjogren syndrome","volume":"12","author":"Francois","year":"2016","journal-title":"Nat Rev Nephrol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2012.05.014","article-title":"B cells in Sjogren\u2019s syndrome: from pathophysiology to diagnosis and treatment","volume":"39","author":"Cornec","year":"2012","journal-title":"J Autoimmun"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key392","article-title":"Is early-onset primary Sjogren\u2019s syndrome a worse prognosis form of the disease","volume":"58","author":"Anquetil","year":"2019","journal-title":"Rheumatol (Oxford)"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(23)00340-5","article-title":"Identification of distinct subgroups of Sjogren\u2019s disease by cluster analysis based on clinical and biological manifestations: data from the cross-sectional Paris-Saclay and the prospective ASSESS cohorts","volume":"6","author":"Nguyen","year":"2024","journal-title":"Lancet Rheumatol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/art.10221","article-title":"Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary Sjogren\u2019s syndrome","volume":"46","author":"Ioannidis","year":"2002","journal-title":"Arthritis Rheum"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.102062","article-title":"Mortality risk factors in primary Sjogren syndrome: a real-world, retrospective, cohort study","volume":"61","author":"Brito-Zeron","year":"2023","journal-title":"EClinicalMedicine"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-206418","article-title":"Systemic activity and mortality in primary Sjogren syndrome: predicting survival using the EULAR-SS Disease Activity Index (ESSDAI) in 1045 patients","volume":"75","author":"Brito-Zeron","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e15284","DOI":"10.1111\/1756-185X.15284","article-title":"Long-term survival analysis of patients with primary Sjogren\u2019s syndrome in China: A multicenter retrospective cohort study","volume":"27","author":"Yueting","year":"2024","journal-title":"Int J Rheum Dis"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1136\/annrheumdis-2019-216114","article-title":"EULAR recommendations for the management of Sjogren\u2019s syndrome with topical and systemic therapies","volume":"79","author":"Ramos-Casals","year":"2020","journal-title":"Ann Rheum Dis"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtauto.2024.100238","article-title":"Treatment of non-systemic Sjogren\u2019s syndrome: Potential prevention of systematization with immunosuppressant agent\/biotherapy","volume":"8","author":"Belbezier","year":"2024","journal-title":"J Transl Autoimmun"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.20452\/pamw.16656","article-title":"Hydroxychloroquine as an important immunomodulator: a novel insight into an old drug","volume":"134","author":"Pawlak-Bus","year":"2024","journal-title":"Pol Arch Intern Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.693796","article-title":"The efficiency of hydroxychloroquine for the treatment of primary Sjogren\u2019s syndrome: A systematic review and meta-analysis","volume":"12","author":"Wang","year":"2021","journal-title":"Front Pharmacol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2015.03.027","article-title":"How are we treating our systemic patients with primary Sjogren syndrome? Analysis of 1120 patients","volume":"27","author":"Gheitasi","year":"2015","journal-title":"Int Immunopharmacol"},{"key":"B31","article-title":"Do antimalarials protect against damage accrual in primary Sjogren\u2019s syndrome? Results from a Latin-American retrospective cohort","author":"Hernandez-Molina","year":"2018","journal-title":"Clin Exp Rheumatol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1772604\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:48:10Z","timestamp":1773298090000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1772604\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,12]]},"references-count":31,"alternative-id":["10.3389\/fimmu.2026.1772604"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1772604","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,12]]},"article-number":"1772604"}}