OP0044 Antibodies anti-saccharomyces cerevisiae in primary sjÖgren's syndrome: prevalence, clinical associations and possible cross-reactivity with disease specific autoantigens
Authors: A Alunno, O Bistoni, F Carubbi, G Cafaro, E Valentini, R Giacomelli, R Gerli
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Saccharomyces cerevisiae is a common yeast used in the food industry. Antibodies against the phosphopeptidomannan part of the cell wall of S. cerevisiae (ASCA) are a well established biomarker of Crohn9s disease and have been assessed in several organ-specific and systemic autoimmune diseases (ADs) (1–2) Although the pathogenic significance of ASCA is not yet fully understood, the molecular mimicry of self-antigens in several associated ADs has been suggested as putative mechanism. <h3>Objectives</h3> Since to date ASCA have not been tested in primary Sjogren9s syndrome (pSS), the purpose of this study was to assess these antibodies in a large cohort of pSS patients and investigate their significance as potentially helpful biomarker in a clinical setting. <h3>Methods</h3> One hundred and four patients with pSS according to the 2002 American European Consensus criteria and 30 healthy donors (HD) were enrolled. ASCA IgG+IgA were assessed in serum samples with ASCA screen dot (Alphadia sa/nv). T cell phenotyping was performed in paired peripheral blood samples by flow cytometry. To compare the aminoacid sequence of mannan of Saccharomyces cerevisiae and well characterized auto-antigens peculiar of pSS (52kD and 60kD Ro/SSA, La/SSB) we browsed the protein database of the National Center for Biotechnology Information (NCBI) and run the Basic Local Alignment Search Tool (BLAST). <h3>Results</h3> ASCA were detected in 5 out of 104 pSS patients, therefore the prevalence in our cohort is 4.8%. None of the ASCA<sup>+</sup> pSS patients displayed IBD or other autoimmune conditions that could account for ASCA positivity. ASCA<sup>+</sup> pSS patients displayed more frequently a reduction of C3 and C4 complement fractions as well as pulmonary, articular and cutaneous involvement (all p&lt;0.05). Binary logistic regression revealed that ASCA<sup>+</sup> pSS patients display an odds ratio of 14 (p=0.006) to have cutaneous manifestations of pSS. All ASCA+ patients but only 39% of ASCA- patients displayed anti-Ro52, anti-Ro60 and anti-La autoantibodies together (p=0.01). No differences concerning T regulatory and Th17 cell proportion could be observed in ASCA<sup>+</sup> compared to ASCA<sup>-</sup> pSS patients. S. cerevisiae mannan displays a consistent similarity with 52kD and 60kD Ro/SSA, La/SSB autoantigens. The highest similarity was observed when aligning the mannan with 60kD Ro/SSA (identities 7/11, 64%; positives 8/11, 72%, E value 2.2.). <h3>Conclusions</h3> Our study assessed for the first time ASCA IgG+IgA with a highly specific immunoblot assay in a large cohort of pSS patients, showing that ASCA positivity identifies a peculiar clinical and serological pSS phenotype. In particular, ASCA<sup>+</sup> pSS patients display anti-Ro52, anti-Ro60 and anti-La antibodies, low complement and cutaneous involvement. The high similarity between S. cerevisiae mannan and Ro60/SSA autoantigen may suggest that: i. ASCA may bind pSS autoantigens, such as anti-Ro, as already postulated for other autoantigens (2); ii. ASCA may bind more likely Ro60 autoantigen rather than the Ro52 or La autoantigens in pSS. A possible pathogenic/prognostic significance of ASCA in pSS may therefore be speculated. <h3>References</h3> Inflamm Bowel Dis 2012;18:1340–1355. Clin Rev Allergy Immunol 2013; 45: 152–61. <h3>Disclosure of Interest</h3> None declared