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.