Background 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 Crohn's 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.
Objectives Since to date ASCA have not been tested in primary Sjogren's 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.
Methods 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).
Results ASCA were detected in 5 out of 104 pSS patients, therefore the prevalence in our cohort is 4.8%. None of the ASCA+ pSS patients displayed IBD or other autoimmune conditions that could account for ASCA positivity. ASCA+ pSS patients displayed more frequently a reduction of C3 and C4 complement fractions as well as pulmonary, articular and cutaneous involvement (all p<0.05). Binary logistic regression revealed that ASCA+ 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+ compared to ASCA- 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.).
Conclusions 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+ 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.
Inflamm Bowel Dis 2012;18:1340–1355.
Clin Rev Allergy Immunol 2013; 45: 152–61.
Disclosure of Interest None declared