Department of Evidence-Based Medicine, Southwest Medical University, 1 Xianglin Road, Luzhou, 646000, Sichuan, China.
Department of Rheumatology and Immunology, Minda Hospital of Hubei Minzu University, 2 Wufengshan Road, Enshi, 445000, Hubei, China.
Inflamm Res. 2023 Jul;72(7):1501-1512. doi: 10.1007/s00011-023-01760-w. Epub 2023 Jun 23.
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.
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 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.
In summary, SHP2 correlated with SLE pathogenesis and promoted the development of lupus.
系统性红斑狼疮（SLE）是一种自身免疫性炎症性疾病。Src 同源 2 结构域蛋白酪氨酸磷酸酶（SHP2）是蛋白酪氨酸磷酸酶（PTPs）家族的成员。迄今为止，SHP2 与 SLE 发病机制之间的关系尚未阐明。
我们通过 ELISA 法测量了 328 例 SLE 患者、78 例 RA 患者、80 例 SS 患者和 79 名健康对照者的血浆 SHP2 水平，并探讨了 SHP2 在 SLE 患者中的相关性，以及血浆 SHP2 作为 SLE 生物标志物的潜力。此外，通过流式细胞术、HE/Masson 检查、免疫荧光试验评估了在注射 SHP2 抑制剂后 pristane 诱导狼疮小鼠的组织学和血清学变化，以揭示 SHP2 在狼疮发病机制中的作用。
结果表明，SLE 患者的 SHP2 血浆水平升高，并与蛋白尿、脓尿等一些临床和实验室特征相关，可能是 SLE 的潜在生物标志物。在 SHP2 抑制剂治疗后，狼疮小鼠的肝脾肿大和肾脏组织学严重程度得到改善。SHP2 抑制剂逆转了 DCs、Th1 和 Th17 细胞的分化，并下调了炎症细胞因子（IL-4、IL-6、IL-10、IL-17A、IFN-γ 和 TNF-α）和自身抗体（ANA、抗 dsDNA）在 pristane 狼疮小鼠中的产生。
总之，SHP2 与 SLE 的发病机制相关，并促进了狼疮的发展。
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