Massachusetts General Hospital Division of Rheumatology Allergy and Immunology, Boston, Massachusetts, USA
Harvard Medical School, Boston, Massachusetts, USA.
Ann Rheum Dis. 2024 Nov 14;83(12):1773-1780. doi: 10.1136/ard-2024-225846.
Hypocomplementaemia is common in patients with IgG4-related disease (IgG4-RD). We aimed to determine the IgG4-RD features associated with hypocomplementaemia and investigate mechanisms of complement activation in this disease.
We performed a single-centre cross-sectional study of 279 patients who fulfilled the IgG4-RD classification criteria, using unadjusted and multivariable-adjusted logistic regression to identify factors associated with hypocomplementaemia.
Hypocomplementaemia was observed in 90 (32%) patients. In the unadjusted model, the number of organs involved (OR 1.42, 95% CI 1.23 to 1.63) and involvement of the lymph nodes (OR 3.87, 95% CI 2.19 to 6.86), lungs (OR 3.81, 95% CI 2.10 to 6.89), pancreas (OR 1.66, 95% CI 1.001 to 2.76), liver (OR 2.73, 95% CI 1.17 to 6.36) and kidneys (OR 2.48, 95% CI 1.47 to 4.18) were each associated with hypocomplementaemia. After adjusting for age, sex and number of organs involved, only lymph node (OR 2.59, 95% CI 1.36 to 4.91) and lung (OR 2.56, 95% CI 1.35 to 4.89) involvement remained associated with hypocomplementaemia while the association with renal involvement was attenuated (OR 1.6, 95% CI 0.92 to 2.98). Fibrotic disease manifestations (OR 0.43, 95% CI 0.21 to 0.87) and lacrimal gland involvement (OR 0.53, 95% CI 0.28 to 0.999) were inversely associated with hypocomplementaemia in the adjusted analysis. Hypocomplementaemia was associated with higher concentrations of all IgG subclasses and IgE (all p<0.05). After adjusting for serum IgG1 and IgG3, only IgG1 but not IgG4 remained strongly associated with hypocomplementaemia.
Hypocomplementaemia in IgG4-RD is not unique to patients with renal involvement and may reflect the extent of disease. IgG1 independently correlates with hypocomplementaemia in IgG4-RD, but IgG4 does not. Complement activation is likely involved in IgG4-RD pathophysiology.
低补体血症在 IgG4 相关疾病（IgG4-RD）患者中很常见。本研究旨在确定与低补体血症相关的 IgG4-RD 特征，并探讨该病中补体激活的机制。
我们对 279 名符合 IgG4-RD 分类标准的患者进行了单中心横断面研究，使用未调整和多变量调整的逻辑回归来确定与低补体血症相关的因素。
90 例（32%）患者出现低补体血症。在未调整模型中，受累器官数量（OR 1.42，95%CI 1.23 至 1.63）和淋巴结受累（OR 3.87，95%CI 2.19 至 6.86）、肺部（OR 3.81，95%CI 2.10 至 6.89）、胰腺（OR 1.66，95%CI 1.001 至 2.76）、肝脏（OR 2.73，95%CI 1.17 至 6.36）和肾脏（OR 2.48，95%CI 1.47 至 4.18）与低补体血症均相关。在调整年龄、性别和受累器官数量后，仅淋巴结（OR 2.59，95%CI 1.36 至 4.91）和肺部（OR 2.56，95%CI 1.35 至 4.89）受累与低补体血症相关，而肾脏受累的相关性减弱（OR 1.6，95%CI 0.92 至 2.98）。纤维化疾病表现（OR 0.43，95%CI 0.21 至 0.87）和泪腺受累（OR 0.53，95%CI 0.28 至 0.999）在调整分析中与低补体血症呈负相关。低补体血症与所有 IgG 亚类和 IgE 的浓度升高相关（均 p<0.05）。在调整血清 IgG1 和 IgG3 后，仅 IgG1 与低补体血症强烈相关，而 IgG4 则无相关性。补体激活可能参与了 IgG4-RD 的病理生理学过程。
