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

Area of Science:

• Immunology
• Rheumatology
• Pathophysiology

Background:

• Hypocomplementaemia is frequently observed in patients diagnosed with IgG4-related disease (IgG4-RD).
• Understanding the clinical features and underlying mechanisms associated with hypocomplementaemia in IgG4-RD is crucial for disease management.

Purpose of the Study:

• To identify specific IgG4-related disease (IgG4-RD) features associated with hypocomplementaemia.
• To explore the mechanisms of complement activation in the context of IgG4-RD.

Main Methods:

• A single-centre cross-sectional study was conducted involving 279 patients meeting IgG4-RD classification criteria.
• Unadjusted and multivariable-adjusted logistic regression analyses were employed to identify factors linked to hypocomplementaemia.

Main Results:

• Hypocomplementaemia was present in 32% of patients.
• Initially, involvement of multiple organs, lymph nodes, lungs, pancreas, liver, and kidneys showed associations with hypocomplementaemia.
• After adjustment, lymph node and lung involvement remained significantly associated, while renal involvement was attenuated. Fibrotic manifestations and lacrimal gland involvement showed inverse associations.
• Hypocomplementaemia correlated with higher concentrations of all IgG subclasses and IgE. Crucially, only IgG1, not IgG4, independently correlated with hypocomplementaemia after adjustment.

Conclusions:

• Hypocomplementaemia in IgG4-RD is associated with the overall extent of the disease and is not exclusive to renal involvement.
• The study highlights a significant independent correlation between IgG1 levels and hypocomplementaemia in IgG4-RD, challenging the role of IgG4.
• These findings suggest that complement activation plays a role in the pathophysiology of IgG4-related disease.