Journal Article

Multiorgan involvement and circulating IgG1 predict hypocomplementaemia in IgG4-related disease

McMahon, Grace A, Liu, Hang, Wallace, Zachary S, Jha, Isha, Katz, Guy, Stone, John H, Jiang, Bohang, Pillai, Shiv S, Perugino, Cory, Atkinson, John Patterson, Guy, Thomas, Zhang, Yuqing, Kim, Alfred Hyoungju, Fernandes, Ana D

2024

Overview

ObjectivesHypocomplementaemia 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.MethodsWe 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.ResultsHypocomplementaemia 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.ConclusionsHypocomplementaemia 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.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited
• Subject: Adult / Aged / Autoimmune Diseases / Classification / Complement activation / Complement Activation - immunology / Complement System Proteins - immunology / Cross-Sectional Studies / Female / Humans / IgG4 related disease / Immune Complex Diseases / Immunoglobulin G / Immunoglobulin G - blood / Immunoglobulin G - immunology / Immunoglobulin G4-Related Disease - blood / Immunoglobulin G4-Related Disease - immunology / Kidney diseases / Laboratories / Lacrimal gland and Nasolacrimal duct / Lymph nodes / Lymphatic system / Male / Medical records / Middle Aged / Patients / Rheumatology / Risk Factors / Vasculitis