Causal relationships between circulating inflammatory factors and IgA vasculitis: a bidirectional Mendelian randomization study

Jiading Qin; Ling Zhang; Bo Ke; Tingting Liu; Chunfang Kong; Chenghao Jin

doi:10.3389/fimmu.2023.1248325

Causal relationships between circulating inflammatory factors and IgA vasculitis: a bidirectional Mendelian randomization study

Front Immunol. 2023 Sep 11:14:1248325. doi: 10.3389/fimmu.2023.1248325. eCollection 2023.

Authors

Jiading Qin^{1

2}, Ling Zhang^{1

2}, Bo Ke^{2

3}, Tingting Liu², Chunfang Kong², Chenghao Jin^{1

2

4}

Affiliations

¹ Medical College of Nanchang University, Nanchang, China.
² Department of Hematology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China.
³ Key Biologic Laboratory of Blood Tumor Cell of Jiangxi Province, Jiangxi Provincial People's Hospital, Nanchang, China.
⁴ National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Soochow, China.

Abstract

Background: IgA vasculitis (IgAV) is an immune-associated vasculitis, yet its exact etiology remains unclear. Here, we explore the interaction between IgAV and inflammatory factors using bidirectional Mendelian randomization (MR).

Methods: We conducted a bidirectional summary-level MR analysis to delineate the causality of C-reactive protein (CRP), procalcitonin (PCT), and 41 circulating inflammatory regulators with IgAV. Data on genetic variants related to inflammation were obtained from three genome-wide association studies (GWASs) on CRP, PCT, and human cytokines, whereas data on IgAV was from large meta-analyses of GWAS among 216 569 FinnGen Biobank participants. The primary MR analysis was performed using the inverse-variance weighted (IVW) approach, and the sensitivity analyses were carried out using MR-Egger, weighted median, weighted mode, and MR-pleiotropy residual sum and outlier.

Results: This study revealed the association of CRP higher levels with increased risk of IgAV through IVW method (Estimate odds ratio [OR] = 1.41, 95% confidence interval [CI]: 1.01-1.98, P = 0.04), MR-Egger (OR = 1.87, CI: 1.15-3.02, P = 0.01), weighted median (OR = 2.00, CI: 1.21-3.30, P = 0.01) and weighted mode (OR = 1.74, CI: 1.13-2.68, P = 0.02). Furthermore, elevated IL-8 was strongly implicated with a higher risk of IgAV (IVW OR = 1.42, CI: 1.05-1.92; P = 0.02). Conversely, genetically predicted IgAV was associated with decreased levels of TNF-β (IVW estimate β = -0.093, CI: -0.178 - -0.007; P = 0.033). Additionally, no such significant statistical differences for other inflammatory factors were found.

Conclusion: Our current study using bidirectional MR analysis provides compelling evidence for a causal effect of CRP, PCT, and circulating inflammatory regulators on IgAV. These findings contribute to a better understanding of the pathogenesis of IgAV and emphasize the potential of targeting inflammatory factors for therapeutic interventions.

Keywords: C-reactive protein; IgA vasculitis; Mendelian randomization; bidirectional; circulating inflammatory regulators.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

C-Reactive Protein / genetics
Genome-Wide Association Study
Humans
IgA Vasculitis* / genetics
Inflammation / genetics
Mendelian Randomization Analysis
Procalcitonin
Vasculitis* / genetics

Substances

C-Reactive Protein
Procalcitonin

Grants and funding

This work was funded by grants from the National Natural Science Foundation of China (No. 82260030) and the Translational Research Grant of NCRCH (No. 2021WWA02).