4. Discussion
There are many studies on pSS and TNFSF13B, mostly focusing on rs9514828, rs1041569, rs9514827, rs12583006 and rs1224141. Most of them have been associated with increased susceptibility to pSS in the literature, but there are subtle differences in opinion. Kintrilis et al. concluded that genotype TT of rs1041569, a variant of the TNFSF13B gene, had a significantly increased prevalence in the pSS patient group compared to healthy controls. It was also demonstrated that genotype TT of rs1041569 was a risk factor for pSS, altering susceptibility to pSS, and that haplotype TTAC was found to increase susceptibility to pSS. The article also concluded that haplotypes TATTT and TTCTT were only detected in pSS patients with thickened arterial walls.2 Santillan-Lopez et al. demonstrated that the expression of TNFSF13B mRNA was increased in pSS patients compared to healthy controls, with a 5.04-fold increase. They also investigated the relationship between soluble BAFF (sBAFF) and TNFSF13B gene expression and found that elevated gene expression levels were consistent with sBAFF protein levels. However, they concluded that TNFSF13B transcript levels in pSS patients were not associated with the gene polymorphism of rs9514828.3 Nezos et al. concluded that the TNFSF13B gene polymorphism increased susceptibility to pSS in both the high-risk group (type I) pSS patients and the low-risk group (type II) pSS patients compared to healthy controls. In the high-risk group of pSS patients, the CC genotype of rs9514828 and the TT genotype of rs9514827 were statistically different from those of healthy controls. In the low-risk group of pSS patients, the minor A allele of rs12583006 and the AA genotype of rs12583006 were statistically different from those of healthy controls.1 Another study identified the TT genotype of the TNFSF13B rs9514828 gene variant as a protective factor against fatigue in patients with pSS.38
As seen in this article, our results demonstrated that the TT genotype of rs1041569, the TT genotype of rs12583006 and the AA genotype of rs12583006 could increase the susceptibility of pSS. These genotypes were statistically significantly related to pSS. On the one hand, we suggested that the TT genotype of rs1041569 and the AA genotype of rs12583006 are risk factors from OR and 95% CI (OR [95% CI], p-value: 4.62[1.59-13.43], p=0.00 and 2.55[1.34-4.86], p=0.00 in the fixed-effects model). On the other hand, we also considered that the TT genotype of rs12583006 is a protective factor from OR and 95% CI (OR [95% CI], p-value: 0.73[0.54-0.99], p=0.04 in the fixed-effects model).
As research has progressed, the role of TNFSF13B in pSS has been explored. Nossent et al. suggested that susceptibility of Ro/La-positive pSS increases with CTAT haplotype and that elevated serum BAFF levels in pSS patients are associated with TTTT haplotype.25Carrillo-Ballesteros et al. concluded that pSS patients with elevated serum BAFF levels had a longer disease duration and the highest levels of anti-La/SSB antibodies. In addition, they found that the duration of the disease was associated with anti-Ro/SSA antibodies and SSDAI scores.6 Loureiro-Amigo et al. determined that BAFF, CXCL13 and PD-L2 showed the highest accuracy in identifying patients with pSS, with significant differences between patients and controls. The most accurate score was obtained by applying BAFF, CXCL13 and PD-L2 levels to the formula [ln(CXCL13) + ln(BAFF)]/ln(PD-L2), which had an Area Under Curve (AUC) value of 0.854, with a sensitivity of 77.2% and specificity of 86.4%, using a cut-off value of 1.7.5 Another research showed that eight of the nine optimal immune-related genes (IRGs) (IL-18, JAK2, TBK1, EED, TNFSF10, TNFSF13B, CYSLTR1, and ICOS) were significantly overexpressed in pSS patients and were defined as key genes by qRT-PCR. ROC analysis showed high sensitivity and specificity for TNFSF13B and CYSLTR1.4
In conclusion, our meta-analysis of the published data demonstrated that polymorphisms in the TNFSF13B gene were related to vulnerability to pSS in the pSS group and healthy controls. The TT genotype of rs1041569 and the AA genotype of rs12583006 were risk factors from OR and 95% CI in pSS patients, and the TT genotype of rs12583006 was a protective factor from OR and 95% CI in pSS patients. As a result, more investigation into the relationship between TNFSF13B, serum BAFF levels, levels of autoantibodies, sensitivity and specificity may shed light on the process by which genetic polymorphisms affect autoantibodies production in patients with pSS, aiding in the clinical diagnosis and therapy of the condition.