Background Primary Sjogren’s syndrome (pSS) is complicated by B-cell lymphoma in 5-10% of patients. Several clinical and serological features are proposed as adverse predictors for such complication and define a high risk pSS phenotype.
Objectives We aimed to explore whether previously described polymorphisms of the B-cell activating factor (BAFF) as well as mutation of its receptor (BAFF-R) could be related to pSS related lymphomagenesis.
Methods Five single nucleotide polymorphisms (SNPs) of the BAFF gene (rs1224141, rs12583006, rs9514828, rs1041569 and the rs9514827) and the BAFF-R mutation His159Tyr were evaluated in 111 low risk pSS patients (type II), 82 high risk/ lymphoma patients (type I) and 137 healthy controls (HC) by PCR-based assays. The classification of pSS patients into type I and II was based on the presence or absence of risk factors or lymphoma development, respectively. Genotype and haplotype analysis was performed for all variants in the pSS groups. Since the rs1041569 SNP was not in Hardy-Weinberg equilibrium in the HC group (p<0.001), haplotypic analysis was performed in the remaining four out of the five SNPs tested when comparisons with HC individuals were performed.
Results The high risk pSS group was characterized by higher frequency of the minor T allele of the rs9514828 BAFF polymorphism compared to HC. Compared to the low risk pSS patients but not the HC, the high risk pSS group exhibited lower frequencies of the AA genotype of the rs12583006 polymorphismas well as the TACAC and TACC haplotypes and higher frequency of the TTTC haplotype. The low risk pSS group exhibited higher frequency of the minor A allele and AA genotype of the rs12583006 variant compared to HC. Both pSS groups were characterized by increased frequency of the haplotype TATT and GTTC and decreased frequency of the TTCT when compared to HC. A significantly increased prevalence of the mutation of BAFF-R His159Tyr was observed in type I pSS patients compared to low risk type II pSS patients (p=0.035) and HC (p=0.003). Such difference was not detected between low risk type II pSS and HC (p=0.47).
Conclusions Taken together, these findings suggest the implication of the host’s genetic background in pSS related lymphomagenesis. The interaction of pSS related BAFF gene haplotypes together with distinct BAFF genetic variants appears to contribute to this complication.
Disclosure of Interest None Declared