ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Prognostic benefit of immunosuppressive agents in primary Sjögren's syndrome patients with hypergammaglobulinemia
Liupan Zhang
Yiwen Zou
Dongyi Chen
Xin Zhang
Zhuoyang Jia
Qingfeng Zhang
Fan Wang
Xuebing Feng
Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
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Abstract
Objective: To elucidate the prognosis of patients with primary Sjögren's syndrome (pSS) accompanied by hypergammaglobulinemia (HG), with a particular focus on the impact of various treatments. Methods: 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 Sjögren's Syndrome Disease Damage Index (SSDDI) score. Results: 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). Conclusion: 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.
Summary
Keywords
Adverse outcome, Hypergammaglobulinemia, Immunosuppressive Agents, prognosis, Sjögren's syndrome
Received
21 December 2025
Accepted
19 February 2026
Copyright
© 2026 Zhang, Zou, Chen, Zhang, Jia, Zhang, Wang and Feng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Liupan Zhang
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