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Significance of high serum IgG4 in complete or non-full-fledged IgG4-related disease—a retrospective investigation of 845 patients and its clinical relevance

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Abstract

Objective

Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized heterogeneous, subacute, and usually silent autoimmune disease involving many organs with protean manifestations. However, high IgG4 in serum is not necessarily indicating an IgG4-RD. The aims of this study were to investigate the clinical relevance of high serum IgG4 level in IgG4-RD or non IgG4-RD patients, and to see if IgG4-RD in Taiwan differs from that in other parts of the world.

Methods

Eight hundred forty-five patients with high IgG4 were retrospectively reviewed from January 2002 to May 2020 in Taipei Veteran General Hospital. Two hundred sixty-seven patients fulfilled IgG4-RD criteria and were categorized into pancreato-hepato-biliary disease, retroperitoneal fibrosis and/or aortitis, head/neck-limited disease, classic Mikulicz syndrome with systemic involvement, CNS-limited disease, sclerosing vasculitis, skin-limited disease, and sensorineural hearing disease. These manifestations were correlated to smoking, atopy, hyper-IgE/eosinophilia, aging, malignancies, and hypocomplementemia. Five hundred seventy-eight patients were not fulfilling the criteria but were also analyzed for the prevalence of allergy, malignancy, connective tissue diseases, lung diseases, and infections.

Results

In IgG4-RD patients, 124 (46.4%) smoked. Top 4 clinical subtypes included Mikulicz syndrome with systemic involvement (33.3%), pancreato-hepatobiliary disease (31.4%), head/neck disease (19.4%), and retroperitoneal fibrosis/aortitis (12.7%). Top 4 co-morbid conditions included high serum IgE/eosinophilia (46.2%), hypocomplementemia (34%), malignancies (13.4%), and allergy (13.4%). Pancreato-biliary disease was associated with high IgE/eosinophilia (r2 = 0.380, P = 0.025) and malignancy (r2 = 0.211, P = 0.027), Miculicz syndrome with allergy (r2 = 0.396, P < 0.01) and high IgE/eosinophil (r2 = 0.396, P < 0.01), CNS diseases (r2 = 0.973, P = 0.035) and sclerosing vasculitis (r2 = 1, P < 0.01) with advanced age respectively, with the latter being also related to atopy and high IgE/eosinophilia (r2 = 1, p < 0.01).

Conclusion

Smoking may precipitate IgG4-RD. IgG4-RD with pancreato-hepatobiliary disease is closely related to allergy and neoplasm, and those with Mikulicz syndrome may result from atopy. Elderly IgG4-RD patients tend to develop CNS pathology parallel to advancing of age. The disease may probably be originated from an unknown mechanism that may sporadically evolve into malignancies.

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Funding

The study was partly supported by the grants from Taipei Veterans General Hospital (V-104C-041) and Ministry of Science & Technology (MOST108-2314-B075-051-MY3), Taiwan.

The report does not contain clinical studies or patient data.

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Authors and Affiliations

  1. Department of Medicine, Division of Allergy and Immunology, Taipei Veterans General Hospital, Taipei, Taiwan

    Hung-Cheng Tsai, Chih-Wei Liu, Chin-Fang Su, Yi-Syuan Sun, Wei-Sheng Chen, Ming-Han Chen, Chien-Chih Lai, Hsien-Tzung Liao & Chang-Youh Tsai

  2. Faculty of Medicine, School of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan

    Hung-Cheng Tsai, Chih-Wei Liu, Chin-Fang Su, Yi-Syuan Sun, Wei-Sheng Chen, Ming-Han Chen, Chien-Chih Lai, Hsien-Tzung Liao, Ying-Ying Yang & Chang-Youh Tsai

  3. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan

    Hsiang-Yun Tung

  4. Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan

    Chih-Wei Liu, Yi-Syuan Sun, Wei-Sheng Chen, Ming-Han Chen, Chien-Chih Lai, Ying-Ying Yang & Chang-Youh Tsai

  5. Department of Medicine, Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan

    Ying-Ying Yang & Yi-Hsiang Huang

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  1. Hung-Cheng Tsai
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Tsai, HC., Tung, HY., Liu, CW. et al. Significance of high serum IgG4 in complete or non-full-fledged IgG4-related disease—a retrospective investigation of 845 patients and its clinical relevance. Clin Rheumatol 41, 115–122 (2022). https://doi.org/10.1007/s10067-021-05772-x

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