2. Academic Validation
  3. SHP2: its association and roles in systemic lupus erythematosus

SHP2: its association and roles in systemic lupus erythematosus

  • Inflamm Res. 2023 Jun 23. doi: 10.1007/s00011-023-01760-w.
Chan Yang # 1,  Rong Li # 1,  Lin-Chong Su # 2,  You-Yu Lan 3,  You-Qiang Wang 4,  Wang-Dong Xu 5,  An-Fang Huang 6
Affiliations

Affiliations

  • 1 Department of Evidence-Based Medicine, Southwest Medical University, 1 Xianglin Road, Luzhou, 646000, Sichuan, China.
  • 2 Department of Rheumatology and Immunology, Minda Hospital of Hubei Minzu University, 2 Wufengshan Road, Enshi, 445000, Hubei, China.
  • 3 Department of Rheumatology and Immunology, Affiliated Hospital of Southwest Medical University, 25 Taiping Road, Luzhou, 646000, Sichuan, China.
  • 4 Department of Laboratory Medicine, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
  • 5 Department of Evidence-Based Medicine, Southwest Medical University, 1 Xianglin Road, Luzhou, 646000, Sichuan, China. loutch123@163.com.
  • 6 Department of Rheumatology and Immunology, Affiliated Hospital of Southwest Medical University, 25 Taiping Road, Luzhou, 646000, Sichuan, China. loutch211@163.com.
  • # Contributed equally.
PMID: 37351631 DOI: 10.1007/s00011-023-01760-w
Abstract

Objective: Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease. Src homology 2 domain containing protein tyrosine Phosphatase (SHP2) is a member of the Protein tyrosine phosphatases (PTPs) family. To date, relationship between SHP2 and SLE pathogenesis is not elucidated.

Method: We measured plasma levels of SHP2 in 328 SLE patients, 78 RA patients, 80 SS patients and 79 healthy controls by ELISA, and discussed association of SHP2 in SLE patients, potential of plasma SHP2 as a SLE biomarker. Moreover, histological and serological changes were evaluated by flow cytometry, HE/Masson examination, immunofluorescence test in pristane-induced lupus mice after SHP2 Inhibitor injection to reveal role of SHP2 in lupus development.

Results: Results indicated that SHP2 plasma levels were upregulated in SLE patients and correlated with some clinical, laboratory characteristics such as proteinuria, pyuria, and may be a potential biomarker for SLE. After SHP2 Inhibitor treatment, hepatosplenomegaly and histological severity of the kidney in lupus mice were improved. SHP2 Inhibitor reversed DCs, Th1, and Th17 cells differentiation and downregulated inflammatory cytokines (IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF-α) and autoantibodies (ANA, anti-dsDNA) production in pristane-lupus mice.

Conclusion: In summary, SHP2 correlated with SLE pathogenesis and promoted the development of lupus.

Keywords

Autoimmunity; Inflammation; Lupus; SHP2.

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