Exploring causal correlations between inflammatory cytokines and systemic lupus erythematosus: A Mendelian randomization

Mengmeng Xiang; Yilun Wang; Zhanyan Gao; Jie Wang; Qian Chen; Zhan Sun; Jun Liang; Jinhua Xu

doi:10.3389/fimmu.2022.985729

Exploring causal correlations between inflammatory cytokines and systemic lupus erythematosus: A Mendelian randomization

Front Immunol. 2023 Jan 19:13:985729. doi: 10.3389/fimmu.2022.985729. eCollection 2022.

Authors

Mengmeng Xiang^{1

2}, Yilun Wang^{1

2}, Zhanyan Gao^{1

2}, Jie Wang^{1

2}, Qian Chen^{1

2}, Zhan Sun^{1

2}, Jun Liang^{1

2}, Jinhua Xu^{1

2}

Affiliations

¹ Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
² Shanghai Institute of Dermatology, Shanghai, China.

Abstract

Objectives: Previous studies have reported that a few inflammatory cytokines have associations with systemic lupus erythematosus (SLE)-for example, IL-6, IL-17, and macrophage inflammatory protein (MIP). This Mendelian randomization was conducted to further assess the causal correlations between 41 inflammatory cytokines and SLE.

Methods: The two-sample Mendelian randomization utilized genetic variances of SLE from a large publicly available genome-wide association study (GWAS) (7,219 cases and 15,991 controls of European ancestry) and inflammatory cytokines from a GWAS summary containing 8,293 healthy participants. Causalities of exposures and outcomes were explored mainly using inverse variance weighted method. In addition, multiple sensitivity analyses including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO were simultaneously applied to strengthen the final results.

Results: The results indicated that cutaneous T cell-attracting chemokine (CTACK) and IL-17 may be suggestively associated with the risk of SLE (odds ratio, OR: 1.21, 95%CI: 1.04-1.41, p = 0.015; OR: 1.37, 95%CI: 1.03-1.82, p = 0.029). In addition, cytokines including beta nerve growth factor, basic fibroblast growth factor, IL-4, IL-6, interferon gamma-induced protein 10, monokine induced by interferon-gamma, MIP1b, stromal cell-derived factor-1 alpha, and tumor necrosis factor-alpha are suggested to be the consequences of SLE disease (Beta: 0.035, p = 0.014; Beta: 0.021, p = 0.032; Beta: 0.024, p = 0.013; Beta: 0.019, p = 0.042; Beta: 0.040, p = 0.005; Beta: 0.046, p = 0.001; Beta: 0.021, p = 0.029; Beta: 0.019, p = 0.045; Beta: 0.029, p = 0.048).

Conclusion: This study suggested that CTACK and IL-17 are probably the factors correlated with SLE etiology, while a couple of inflammatory cytokines are more likely to be involved in SLE development downstream.

Keywords: GWAS; Mendelian randomization; biomarkers; inflammation; systemic lupus erythematosus.

Publication types

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

MeSH terms

Causality
Cytokines* / genetics
Genome-Wide Association Study
Humans
Interferon-gamma / genetics
Interleukin-17 / genetics
Interleukin-6 / genetics
Lupus Erythematosus, Systemic* / genetics
Mendelian Randomization Analysis

Substances

Cytokines
Interleukin-17
Interleukin-6
Interferon-gamma

Grants and funding

This research was financially supported by the National Natural Science Foundation of China (grant number no. 82073443, no. 81773324, and no. 81703122) and Shanghai Municipal Key Clinical Specialty (no. shslczdzk01002).