Clinical Characteristics of Patients With IgG4-Related Disease Complicated by Hypocomplementemia

Abstract

BackgroundA proportion of patients with immunogloblin G (IgG) 4-related disease (IgG4-RD) have hypocomplementemia. We aimed to identify characteristics of such patients.MethodsWe 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.ResultsThirty-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).ConclusionsPatients with IgG4-RD with hypocomplementemia have a more active clinical phenotype, suggesting contributions of the complement system in the pathophysiology of IgG4-RD.

Correlation between serologic parameters and disease activity of IgG4-related disease: Differences between patients with normal and elevated serum IgG4 concentrations

“…Subsequent study on 12 patients with IgG4-RD from the same group reported that serum IgG4, particularly that with flucosylation change, may be associated with complement activation (19). In contrast, more recent studies with larger number of patients (n = 85 (20); and n = 328 ( 21)) suggested that hypocomplementemia in IgG4-RD is associated with IgG subclasses other than IgG4. Indeed, immune complexes that contain IgG4 bind complement weakly; hypocomplementemia in IgG4-RD results from immune complexes containing IgG1 or IgG3 rather than IgG4 (2,22,23).…”

Performance of classification and diagnostic criteria for IgG4-related disease and comparison of patients with and without IgG4-related disease

“…A previous study reported hypocomplementemia and low serum CRP levels in IgG4-RD 23 ; we had similar results in this study. The mechanism underlying hypocomplementemia in IgG4-RD remains unclear, but it has been reported that IgG4-RD with hypocomplementemia is associated with more kidney or lung involvement and relapse 17 . Since serum CRP levels are often elevated in mimickers such as multicentric Castleman disease 5 , we might have identified a significant difference in serum CRP levels among patients with versus without IgG4-RD with a single affected organ.…”

“…We collected clinical data, including patient demographics, laboratory data at diagnosis, and outcomes, from medical records. The number of involved organs was counted from 11 lesions, based on a previous study 17 . The sensitivity and specificity of the 2019 ACR/EULAR classification criteria and the 2020 RCD criteria were evaluated by rheumatologists.…”