LAUSR

The incidence of Crohn’s disease (CD) in industrialized countries has increased steadily due to improvements in the standard of living since the Second World War [1]. CD is characterized by an uncontrolled immune response within the intestinal mucosa. The activation and/or chronicity of the inflammatory response depends on genetic susceptibility to various environmental stimuli, including the intestinal flora [2]. The development of CD is associated with the sequential appearance of antibodies against microbial molecular motifs, the levels of which remain stable once the disease has become established. These antibodies, initially used for diagnostic purposes, are now used for CD clinical management. The number of antigenic targets and the magnitude of the response, are indicative of disease severity [3], are now taken into account when defining the nature of initial treatment[4]. Similarly, their pre-existence to CD onset is increasingly considered in surveys of high risk populations[5]. Despite their widespread use, the mechanisms of generation and persistence of these antibodies remain unknown. Anti-Saccharomyces cerevisiae antibodies (ASCA) are the most widely used of these antibodies. A recent paper involving murine models reported that the inability of S. cerevisiae to catabolize purines affects host metabolism through uric acid (UA) production and that this may negatively affect the course of inflammatory bowel disease (IBD) [6]. As an argument in favour of this hypothesis, a correlation between ASCA and UA was reported in healthy subjects. Because of the impact of this conclusion, which suggests that S. cerevisiae is potentially pathogenic in human beings, especially those susceptible to developing CD, we carried out experiments to investigate this correlation. We measured UA and ASCA levels in our cohorts of IBD patients and controls. Our conclusion was that this correlation does not exist and we think it important to publish these data and to extend the discussion to the significance of ASCA, the role of S. cerevisiae and, more generally, the role of yeasts in CD. Our investigations involved two cohorts of IBD patients included in previous studies comprising ASCA levels determination. Sera collected from four groups of patients were analyzed. The first serum repository (CD1) consisted of 28 sera collected from 28 patients (nine male/19 female; mean age: 27.5 years; age at diagnosis: 21 years; location of disease: ileal (L1; n = 22), colonic (L2; n = 0), ileocolonic (L3; n = 6) selected on the basis of high ASCA levels associated with CD complications needing ileocecal resection. The sera were taken the day before surgery [Effect of Fluconazole on the Levels of Anti-Saccharomyces cerevisiae Antibodies (ASCA) After Surgical Resection for Crohn’s Disease. Multicenter, Randomized, and Controlled in Two Parallel Groups Versus Placebo. ClinicalTrialsgov ID: NCT02997059]. The second serum repository (CD2) came from genetic and functional studies of IBD patients [French Ministry for Health, Programme Hospitalier de Recherche Clinique, Etudes génétique et fonctionnelle des patients atteints de maladies inflammatoires chroniques de l’intestin; Grant 2006-Lille19-01]. This consisted of 85 sera from 49 CD patients (14 male/35 female; mean age: 26 years; age at diagnosis: 20 years; location of disease: L1 (n = 11), L2 (n = 4), L3 (n = 34). The third serum repository (UC) was collected from 36 patients with ulcerative colitis (male/female: 20/16; mean age: 34 years, age at diagnosis: 31 years) with the following phenotypes at diagnosis: proctitis (E1; n = 11),