Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Front Immunol. 2022 Feb 24;13:828122. doi: 10.3389/fimmu.2022.828122. eCollection 2022.
A proportion of patients with immunogloblin G (IgG) 4-related disease (IgG4-RD) have hypocomplementemia. We aimed to identify characteristics of such patients.
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.
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).
Patients with IgG4-RD with hypocomplementemia have a more active clinical phenotype, suggesting contributions of the complement system in the pathophysiology of IgG4-RD.
一部分免疫球蛋白 G（IgG）4 相关疾病（IgG4-RD）患者存在低补体血症。本研究旨在明确此类患者的临床特征。
我们分析了 85 例 IgG4-RD 患者的人口统计学和临床资料以及补体水平。我们将低补体血症定义为初诊时血清 C3 和（或）C4 水平低于正常值下限。我们还比较了 IgG4-RD 患者有无低补体血症的临床特征。
32 例（38%）患者初诊时存在低补体血症。与无低补体血症者相比，低补体血症患者淋巴结（p < 0.01）、肺（p < 0.01）和肾脏（p = 0.02）受累更常见，且 IgG4-RD 应答指数更高（p = 0.05）。此外，低补体血症患者 IgG（p < 0.01）、IgG4（p < 0.01）和可溶性白细胞介素 2 受体（sIL-2R）（p < 0.01）水平以及 IgG 减去 IgG4（p < 0.01）差值均显著升高。C3 和 C4 水平与 IgG、IgG4 和 sIL-2R 水平、IgG 减去 IgG4 差值以及 IgG4-RD 应答指数呈负相关，该指数是 IgG4-RD 疾病活动度的一种衡量标准。用对数秩检验分析发现，低补体血症患者的复发频率显著更高（p = 0.024）。多变量 logistic 回归分析显示，低补体血症的存在与复发独立相关（OR，6.842；95%CI，1.684-27.79；p = 0.007）。
伴有低补体血症的 IgG4-RD 患者具有更活跃的临床表型，提示补体系统可能参与了 IgG4-RD 的病理生理学过程。
