SHP2: its association and roles in systemic lupus erythematosus

ObjectiveSystemic 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.MethodWe 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.ResultsResults 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-& gamma; and TNF-& alpha;) and autoantibodies (ANA, anti-dsDNA) production in pristane-lupus mice. ConclusionIn summary, SHP2 correlated with SLE pathogenesis and promoted the development of lupus.

Automated summary

This study found that the levels of SHP2 were significantly upregulated in SLE patients and correlated with some clinical and laboratory characteristics, suggesting its potential as a biomarker for SLE. Treatment with a SHP2 inhibitor in a mouse model improved hepatosplenomegaly and histologic severity of the kidney, and reversed differentiation of DCs, Th1, and Th17 cells, as well as downregulated production of inflammatory cytokines and autoantibodies.