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Comparative Study
. 2025 Jul 7:16:1607074.
doi: 10.3389/fimmu.2025.1607074. eCollection 2025.

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

Rajalingham Sakthiswary  1 , Syahrul Shaharir  1 , Asrul Abdul Wahab  1 , Veshaaliini Uma Rajeswaran  1
Affiliations
Comparative Study

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

Rajalingham Sakthiswary et al. Front Immunol. .

Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Keywords: cytokine; disease activity; immunoglobulin G; joint erosions; rheumatoid arthritis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Correlation between IgG4 levels and (A) DAS28 (B) HAQDI and (C) MSS.
Figure 2
Figure 2
IgG4 and cytokine levels according to disease activity.
Figure 3
Figure 3
IgG4 and cytokine levels in erosive disease.
See this image and copyright information in PMC

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