A9.04 SNPS in the baff gene are associated with increased risk of anti-jo-1-positivity and high serum baff levels in patients with myositis
Authors: O Kryštůfková, T Svitálková, H Hulejová, M Světlá, L Pleštilová, M Pavlíková, M Mišunová, M Klein, H Mann, P Novota, J Vencovský
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> B-cell activating factor of the TNF family (BAFF) plays a role in (auto)antibody production. Elevated serum levels (sBAFF) were found in patients with myositis. Associations of elevated sBAFF with a SNP in the 5´regulatory region of the BAFF genewere reported in patients with autoimmune diseases, together with TTTT haplotype of the&nbsp;four SNPs located upstream of the BAFF gene. TTTT was associated with myositis in Czech patients, independently from the HLA-DRB1*03 allele. Here we evaluate associations of sBAFF with particular SNPs, anti-Jo-1-autoantibodies, HLA-DRB1*03, ILD and disease activity in myositis. <h3>Materials and methods</h3> The SNPs (rs9514828:871C&gt;T, rs9514827:-2841T&gt;C, rs3759467:-2704T&gt;C and rs1041569:-2701T &gt;A) were analysed by direct DNA sequencing in 311 patients with myositis (age:58.0 ± 14.5(years), females = 74%) and 113 healthy controls (age:40.6 ± 14.3, females = 70%). Levels of sBAFF were measured by ELISA. Autoantibodies were detected by immunoprecipitation. Multivariable logistic regression model for presence of anti-Jo-1-autoantibodies and nonparametric tests for group comparisons and correlation analysis were used. <h3>Results</h3> Analysed patients&nbsp;cohort included&nbsp;150 DM, 139 PM, 51%&nbsp;ILD and 24% anti-Jo-1-positive patients. HLA-DRB1*03 was present in 45% of patients and 16% of controls. Higher s-BAFF levels were detected in: patients compared to healthy controls (p &lt; 0.0001), patients with anti-Jo-1-autoantibodies compared to autoantibody negative (p = 0.02), patients with early (duration≤ 6 month; n = 114) compared to late disease (p = 0.038) and were associated with creatine kinase (CK) levels (rho=0.36;p &lt; 0.0001) and disease duration (rho=-0.2;p = 0.0007). Logistic regression model explaining 49% (McFadden R<sup>2</sup>=0.49) of the data variability included, besides ILD (OR = 27.24;p &lt; 0.0001) and HLA-DRB1*03 (OR = 5.26;p = 0.0009), significant additive effect of the BAFF gene SNPs: -2841T allele (OR = 2.55;p = 0.028) and a -871TT genotype (OR = 7.75;p = 0.007). The&nbsp;alternative substitution of CK concentration (OR = 1.48;p = 0.175) with sBAFF (OR = 0.67; p = 0.037)lowered model stability (R<sup>2</sup> = 0.38). However, the additive effect of -871T allele to sBAFF levels in anti-Jo-1-positive patients compared to autoantibody-negative (higher in -871TT:p = 0.023 and -871CT:p = 0.043) and the opposite association in -2841TT genotype (higher in -2841CC: p = 0.033 and -2841CT:p = 0.068)were seen. <h3>Conclusion</h3> In addition to ILD and HLA-DRB1*03 allele, SNPs of the promotor&nbsp;region of the BAFF gene, -871C &gt;T and -2841T &gt;C, increase the risk of having anti-Jo-1-autoantibodies and high sBAFF levels in patients with myositis. <h3>Acknowledgements</h3> MZČR-Institutional support of research organisation-00023728.