Association of B7H3 and B7H4 gene polymorphisms and protein expression with the development and prognosis of autoimmune thyroid diseases.

Abstract

The prognosis of autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's disease (HD), varies among patients. B7-H3 and B7-H4, members of the B7 family of proteins, regulate immune response. To clarify the association of B7-H3 and B7-H4 with the pathogenesis and prognosis of AITDs, we examined the expression of the soluble and membrane form of B7-H3 and B7-H4 and genotyped single nucleotide polymorphisms (SNPs) in the B7H3 and B7H4 genes. We examined the expression of the membrane form of B7-H3 and B7-H4 by flow cytometry and their soluble forms by enzyme-linked immunosorbent assay. We genotyped SNPs in B7H3 and B7H4 in 187 GD patients, 217 HD patients, and 110 healthy volunteers using the PCR-RFLP method. The frequency of the B7H3 rs3816661 CC genotype was higher in patients with severe HD. G carriers of B7H4 rs10754339 A/G and B7H4 rs13505 T/G were more frequent in patients with AITD. A carrier of B7H4 rs10158166 A/G and C carriers of B7H4 rs3806373 C/T were more frequent in patients with intractable GD. The proportion of B7-H3+ monocytes was higher in the CC genotype of B7H3 rs3816661 C/T than in the other genotypes and was lower in patients with GD and HD than in healthy controls. The concentration of soluble B7-H4 was lower in the TG genotype of B7H4 rs13505 T/G than in the TT genotype and was higher in patients with AITD than in healthy controls. B7H3 and B7H4 are associated with AITD susceptibility and prognosis.