Comparison of IgG4 with inflammatory cytokines (IL-1, IL-6 and TNFα) in rheumatoid arthritis

TL;DR

This study compares IgG4 and inflammatory cytokines in rheumatoid arthritis patients, finding IgG4 is more closely linked to disease activity than expected.

Contribution

The study reveals IgG4's stronger association with RA disease activity compared to traditional cytokines like IL-1, IL-6, and TNFα.

Findings

IgG4 levels correlated moderately with IL-6 but not with IL-1 or TNFα.

IgG4 showed significant correlations with DAS28, MSS, and HAQ-DI scores.

TNFα and IL-6, but not IL-1, correlated with radiographic joint erosion severity.

Abstract

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic joint inflammation driven by a complex interplay of autoantibodies, cytokines, and chemokines. While the role of proinflammatory cytokines, such as interleukin-1(IL-1), interleukin-6(IL-6), and tumor necrosis factor-α (TNF-α), in the pathogenesis of RA has been well-established, the contribution of the immunoglobulin G subclass IgG4 remains a topic of ongoing investigation. This cross sectional study aim was to compare the levels of IgG4 and these key inflammatory cytokines in Malaysian patients with RA.

The study enrolled a total of 194 RA patients. All subjects were tested for their serum IgG4, IL-1, IL-6 and TNF-α levels. Besides, subjects were assessed for their disease activity based on DAS28, functional disability based on HAQ-DI (Health Assessment Questionnaire-Disability Index) and the severity of the radiographic joint erosions by using the Modified Sharp Score (MSS).

Correlation analysis revealed a moderate positive association between IgG4 and IL-6 levels (r=0.348, p=0.001), but there were no significant correlations with IL-1 and TNFα levels. IgG4 levels showed a significant positive correlation with DAS28, MSS, and HAQ-DI. All 3 cytokine levels had significant relationships with the DAS28 scores, but for the MSS, only TNF-α (p=0.024) and IL-6 (p=0.016) demonstrated significant associations. None of the cytokines correlated significantly with the HAQ-DI scores.

The positive correlation between IgG4 and IL-6 levels underscores the possibility for IL-6-driven pathways to influence IgG4 production. Serum IgG4 was associated with more clinical aspects of RA compared to the classical inflammatory cytokines.

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