B-lymphocyte-activating factor is a potential biomarker associated with susceptibility to Graves’ disease in Iraqi women

Abstract

Background B-lymphocyte-activating factor (BAFF) is a cytokine involved in regulating the development and maturation of B lymphocyte and has been shown to be up-regulated in patients with Graves’ disease (GD). However, the association of TNFSF13B variants (the gene that encodes BAFF) with the risk of GD has not been well explored. In this case–control study, the aim was to evaluate the role of BAFF, in terms of serum level and polymorphism, in the etio-pathogenesis of GD. Therefore, serum BAFF concentrations were analyzed in Iraqi women with GD and age-matched control women (n = 90 and 93, respectively) using an ELISA kit. In addition, two promoter variants of the TNFSF13B gene, rs9514827 (T > C) and rs9514828 (C > T), were genotyped using a PCR–RFLP-based assay. Results Median BAFF concentrations (interquartile range) were significantly elevated in GD patients compared to controls (1525 [1327–1840] vs. 689 [585–807] pg/mL; probability [p] < 0.001). Elevated BAFF concentrations were a reliable predictor of GD as indicated by the area under the curve of 0.971. BAFF was positively correlated with triiodothyronine (correlation coefficient [rs] = 0.216; p = 0.041) and thyroxine (rs = 0.269; p = 0.01) in GD patients. Mutant alleles, rs9514827 C (odds ratio [OR] = 2.00; p = 0.008; corrected p [pc] = 0.048) and rs9514828 T (OR = 2.15; p = 0.002; pc = 0.012), as well as genotypes, rs9514827 CC (OR = 4.29; p = 0.032; pc = 0.192) and rs9514828 TT (OR = 4.57; p = 0.003; pc = 0.018), were associated with a greater risk of GD. Besides, the C-T haplotype (rs9514827-rs9514828) was also linked to an elevated risk of GD among Iraqi women (OR = 2.71; p = 0.006; pc = 0.024). Conclusions BAFF showed up-regulated levels in the serum of women with GD. In light of this, BAFF has been proposed as a reliable prognostic biomarker for GD. Regarding its relationship to thyroid hormones, BAFF showed a positive correlation with triiodothyronine and thyroxine. Both variants (rs9514827 and rs9514828) of the TNFSF13B gene showed an association with susceptibility to GD, and rs9514828 may have up-regulatory effects on BAFF levels.