Evaluation of the role of B7-H3 haplotype in association with impaired B7-H3 expression and protection against type 1 diabetes in Chinese Han population

Abstract

Background: Type 1 Diabetes (T1D) is a T cell-mediated autoimmune disorder caused by the destruction of insulinsecreting cells. B7-H3 (CD276) plays a vital role in T cell response. However, B7-H3 expression and its clinical significance in T1D remain unclear. The aim of this study was to investigate the correlations between the expression of B7-H3 and clinical parameters in T1D patients. The possible role of B7-H3 gene variants with T1D was also discussed. Methods: Four B7-H3 single nucleotide polymorphisms (SNPs) were genotyped in 121 T1D patients and 120 healthy controls by polymerase chain reaction (PCR) direct sequencing. Expression of membrane B7-H3 (mB7-H3) in peripheral blood lymphocytes was determined by flow cytometry. Levels of soluble B7-H3 (sB7-H3) in serum were analyzed by enzyme linked immunosorbent assay (ELISA). Results: The B7-H3 haplotype T-A-C-T was less frequently observed in T1D patients compared to the controls (OR: 0.31, 95% CI: 0.16-0.61). B7-H3 expression on monocytes showed significant upregulation in T1D patients and was positively correlated with several clinical features including ALT, fast C-peptide 120 min, HbAlc, IFN-γ, IL-6 and TNF-α (P < 0.05). The concentration of sB7-H3 in serum increased in T1D patients (P < 0.0001). We also observed that B7-H3-T-A-C-T was associated with the decreased release of sB7-H3 but not the membrane form. Conclusions: B7-H3 may act as a potential biomarker related to the pathogenesis of T1D. The B7-H3-T-A-C-T polymorphism variant is associated with the low risk of T1D as well as less release of sB7-H3.

Association analysis of B7‐H3 and B7‐H4 gene single nucleotide polymorphisms in susceptibility to ankylosing spondylitis in eastern Chinese Han population

“…B7‐H3 was found to promote osteoblast differentiation and bone mineralization (Suh et al., 2004). Moreover, several polymorphisms of B7‐H3 have been revealed to be associated with autoimmune diseases including RA and T1D (Ding et al., 2020; Sun et al., 2015). However, in our study, we did not find any of the two SNPs of B7‐H3 to be associated with AS.…”

“…Over the past decades, a number of studies have confirmed the vital role of B7‐H3 and B7‐H4 in cancers, inflammatory and autoimmune diseases and organ transplantation (Chen et al., 2020; Wang & Wang, 2020). B7‐H3 and B7‐H4 gene polymorphisms were also shown to be associated with the susceptibility to several autoimmune disorders, including rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) and type 1 diabetes (T1D) (Daha et al., 2012; Ding et al., 2020; Reinards et al., 2015; Sun et al., 2015). Nevertheless, so far, no studies have investigated the association between the single nucleotide polymorphisms (SNPs) of B7‐H3 and B7‐H4 genes and the risk of AS.…”