Possible Involvement of Circulating Immune Complex Containing IgG4 in the Pathogenesis of IgG4-Related Disease Complicated by Hypocomplementemia: A Case Report

TL;DR

A case report suggests that IgG4-containing immune complexes may contribute to kidney damage in IgG4-related disease through complement activation.

Contribution

This case report provides evidence that IgG4-containing immune complexes may activate the complement system in IgG4-related disease.

Findings

The patient's CICs were predominantly composed of IgG4.

Complement components were deposited in the renal tubules, indicating local complement activation.

Glucocorticoid therapy improved renal function and serological abnormalities.

Abstract

Studies examining IgG subclasses within circulating immune complexes (CICs) in patients with IgG4-related disease remain scarce. A Japanese man in his 50s with a history of diabetes mellitus and chronic pancreatitis was referred to our department because of an increase in serum creatinine levels. Serum IgG and IgG4 levels were markedly high, accompanied by eosinophilia and elevated serum IgE levels. C3 hypocomplementemia and an increase in CICs were also noted, and imaging revealed swollen mediastinal lymph nodes. Renal biopsy revealed extensive tubulointerstitial nephritis with numerous IgG4-positive plasma cells and dense interstitial fibrosis. The patient was diagnosed with IgG4-related disease, and glucocorticoid therapy was initiated; renal function, serological abnormalities, and swelling of the mediastinal lymph nodes improved. Subsequent analyses revealed that the patient’s CICs mainly comprised IgG4 and that there was tubular deposition of complement components C1q, C4d, C3, and C5b-9 in the renal biopsy tissue, suggesting that immune complexes containing IgG4 activated the complement pathway in circulation and locally in the kidneys. Hypocomplementemia and CICs are observed in a subset of patients with IgG4-related diseases; however, the underlying mechanisms remain unclear. Further accumulation of IgG4-related disease cases is required to evaluate the possibility of IgG4-mediated complement activation.

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