AUTHOR=Fujita Yuya , Fukui Shoichi , Umeda Masataka , Tsuji Sosuke , Iwamoto Naoki , Nakashima Yoshikazu , Horai Yoshiro , Suzuki Takahisa , Okada Akitomo , Aramaki Toshiyuki , Ueki Yukitaka , Mizokami Akinari , Origuchi Tomoki , Watanabe Hiroshi , Migita Kiyoshi , Kawakami Atsushi TITLE=Clinical Characteristics of Patients With IgG4-Related Disease Complicated by Hypocomplementemia JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.828122 DOI=10.3389/fimmu.2022.828122 ISSN=1664-3224 ABSTRACT=Background

A proportion of patients with immunogloblin G (IgG) 4-related disease (IgG4-RD) have hypocomplementemia. We aimed to identify characteristics of such patients.

Methods

We analyzed the demographic and clinical data and complement levels of 85 patients with IgG4-RD. We defined hypocomplementemia as serum C3 and/or C4 levels below the lower limit of normal at diagnosis. We also compared the characteristics of patients with and without IgG4-RD.

Results

Thirty-two (38%) patients had hypocomplementemia at diagnosis. Patients with hypocomplementemia had more lymph node (p < 0.01), lung (p < 0.01), and kidney (p = 0.02) involvement and a higher IgG4-RD responder index than those without (p = 0.05). Additionally, patients with hypocomplementemia had significantly higher IgG (p < 0.01), IgG4 (p < 0.01), and soluble interleukin 2-receptor (sIL-2R) (p < 0.01) levels and total IgG minus IgG4 (p < 0.01). C3 and C4 levels negatively correlated with IgG, IgG4, and sIL-2R levels, total IgG minus IgG4, and number of IgG4-RD responder index: a measure of the disease activity in IgG4-RD. Patients with hypocomplementemia at diagnosis had a significantly higher frequency of relapse (p = 0.024), as determined using the log-rank test. A multivariate logistic regression analysis showed the presence of hypocomplementemia was independently associated with relapse (OR, 6.842; 95% confidence interval [95%CI], 1.684–27.79; p = 0.007).

Conclusions

Patients with IgG4-RD with hypocomplementemia have a more active clinical phenotype, suggesting contributions of the complement system in the pathophysiology of IgG4-RD.