Mechanisms of Tumor Necrosis Factor-Alpha Inhibitor-Induced Systemic Lupus Erythematosus

Chung-Yang Yen; Sheng-Jie Yu; Yi-Ming Chen; Kuo-Lung Lai; Yi-Da Wu; En-Chih Liao; Ching-Liang Hsieh

doi:10.3389/fmed.2022.870724

Mechanisms of Tumor Necrosis Factor-Alpha Inhibitor-Induced Systemic Lupus Erythematosus

Front Med (Lausanne). 2022 Jun 6:9:870724. doi: 10.3389/fmed.2022.870724. eCollection 2022.

Authors

Chung-Yang Yen^{1

2}, Sheng-Jie Yu³, Yi-Ming Chen⁴, Kuo-Lung Lai⁴, Yi-Da Wu⁴, En-Chih Liao⁵, Ching-Liang Hsieh^{6

7}

Affiliations

¹ Department of Dermatology, Taichung Veterans General Hospital, Taichung City, Taiwan.
² School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
³ Department of Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan.
⁴ Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan.
⁵ Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.
⁶ Chinese Medicine Research Center, China Medical University, Taichung City, Taiwan.
⁷ Department of Chinese Medicine, China Medical University Hospital, Taichung City, Taiwan.

Abstract

Systemic lupus erythematosus induced by biologics mainly results from tumor necrosis factor-alpha remains unclear. The objectives of the study were to investigate the mechanisms of tumor necrosis factor-alpha inhibitor-induced systemic lupus erythematosus. Peripheral blood mononuclear cells obtained from thirteen psoriasis patients were cultured and treated with the following: untreated control, Streptococcus pyogenes with or without different biologics. The supernatants were collected for cytokines assay. Analysis of cytokine expression revealed that IL-2 and IL-10 levels decreased only in the TNF-α inhibitor-treated groups but not in the groups treated with biologics involving IL-17, IL-12/IL-23 or IL-23 inhibitor mechanisms (p < 0.001, p < 0.05). The IFN-γ/IL-13 ratio increased significantly in patients with SLE inducing biologics to S. pyogenes induction only compared with non-SLE inducing biologics to S. pyogenes induction only (p = 0.001). IL-2 and IL-10 depletion and a shift to the Th-1 pathway in the innate response are the correlated mechanism for tumor necrosis factor-alpha inhibitor-induced systemic lupus erythematosus.

Keywords: IFN-γ/IL-13 ratio; IL-10; IL-2; systemic lupus erythematosus; tumor necrosis factor-alpha inhibitors.