Background B-cell activating factor of the TNF family (BAFF)is important for B cell maturationand plays a role in (auto)antibodies production. Elevated serum levels in relation to autoantibodies were documented in patients with IIMs. Promoter region of BAFF gene contains several known sites with single nucleotide polymorphism (SNPs). An association between rs9514828 (-871 C/T) SNP and susceptibility to idiopathic thrombocytopenic purpura was shown and possible relations to systemic lupus erythematosus, rheumatoid arthritis or Sjögren’s syndrome were suggested.

Objectives To describe four BAFF SNPs located in the BAFF gene promoter in patients with IIMs and analyze relation of particular SNPs to serum BAFF (s-BAFF) levels in autoantibody positive patients.

Methods Patients with polymyositis (n=146), dermatomyositis (DM, n=150), juvenile DM (n=11), inclusion body myositis (n=4) and 103 healthy individuals were included. Four SNPs located upstream in the BAFF gene (rs9514827 (-2841 T/C); rs3759467 (-2704 T/C); rs1041569 (-2701 T/A); rs9514828 (-871 C/T)) were analyzed by direct DNA sequencing. Levels of s-BAFF were measured using ELISA. Autoantibodies were detected with immunoprecipitation and Line blot assay. The chi square test for analysis of alleles and genotypes associations and SNPStats software for haplotype frequency studies wereused.

Results Significantly higher frequency of -2701T allele was present in patients (18%) compared to healthy controls (12%) (p=0.029; OR 1.68 (CI 95%=1.05-2.7)). Additionally, increased -2841T allele (p=0.09), -2841TT, CT genotype (p=0.07) and -2701TT, AT genotype (p=0.08) frequencies were observed in patients. SNPs were in strong linkage disequilibrium and formed four common haplotypes (TTAC, CTAT, TCAC, TTTT), with significantly different frequency (> 9%) distributions between patients and controls (global P=0.038). Higher frequency of TTTT haplotype was present in patients (16%) compared to controls (9%; OR 1.99 (95% CI 1.15-3.47; P=0.015)) relative to the most frequent haplotype TTAC. Significantly higher s-BAFF levels were detected in patients compared to healthy controls (P<0.0001) and in patients with anti-Jo-1 or anti-PMScl autoantibodies compared to patients without autoantibodies (P=0.028, P=0.037 respectively). Within anti-Jo-1 positive patients, higher s-BAFF levels in patients with -2704T allele compared to patients with -2704C allele (p=0.03) were detected.

Conclusions -2701T allele and TTTT haplotype in the four SNPs located upstream of the BAFF gene were associated with the presence of myositis. Patients with anti-Jo-1 antibodies have higher BAFF levels if they are carriers of -2704T allele. These findings point to differential genetic regulation of BAFF production in patients with IIMs, but need to be validated in the second independent cohort of patients.

Acknowledgements Grant support of IGA -Ministry of Health of the Czech Republic NT/12438-4.

Disclosure of Interest None Declared