# 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.

## Key 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.