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Bacillus Calmette-Guerin (BCG) and Mycobacterium avium subspecies paratuberculosis (MAP) have been associated with multiple sclerosis (MS). Clinical data indicates that BCG vaccination exerts anti-inflammatory effects in MS; conversely, MAP is thought to be one of the possible infectious factors responsible of MS through a molecular mimicry mechanism. A peptide-based indirect ELISA was used to detect antibodies against the encephalitogenic myelin oligodendrocyte glycoprotein (MOG)35–55 epitope, and two mycobacterial peptides sharing sequence homology with the latter: MAP_2619c352–361/BCG_1224355–364 and BCG_3329c64–74. Among 40 MS patients and 39 healthy volunteers included in the study, only MOG35–55 was capable of inducing a significantly higher humoral response in MS subjects compared to controls. Indeed, 11 out of 40 MS subjects (27.5%) and only 2 out of 39 controls (5%) were antibody-positive for MOG35–55 (p = 0.01, AUC = 0.65). These findings strengthen the importance of MOG35–55 in MS pathogenesis. The MAP and BCG MOG-homologues epitopes investigated were not recognized in MS patients. Overall, the results allow us concluding that sharing homology of linear epitopes is necessary but not sufficient to induce antibody-mediated cross-reactivity.

Epstein–Barr virus and Mycobacterium avium subsp. paratuberculosis (MAP) have been associated to multiple sclerosis (MS). We searched for antibodies against the homologous peptides Epstein–Barr virus nuclear antigen 1 (EBNA1)400–413, MAP_0106c protein (MAP)121–132, and myelin basic protein (MBP)85–98 on a MS Sardinian cohort, showing that these antibodies are highly prevalent among MS patients compared to healthy controls. Competitive assay demonstrated that antibodies recognizing EBNA1400–413 and MAP121–132 cross-react with MBP85–98, possibly through a molecular mimicry mechanism. Indeed, the fact that peptides from different pathogens can be cross-recognized by antibodies targeting self-epitopes supports the hypothesis that EBV and MAP might trigger autoimmunity through a common target.

Mycobacterium avium ss. paratuberculosis (MAP) is an intracellular pathogen recently associated with multiple sclerosis (MS). Aiming to identify immunodominant epitopes belonging to MS related protein MAP2694 (UniProt accession no. Q73WG6), we investigated the binding activity of selected peptides against MS Sardinian sera. An overlapping 9-mers peptide library was synthesized spanning the entire aminoacidic sequence of the protein. Peripheral blood was collected from 47 MS patients and 42 sex and age matched healthy volunteers and subjected to enzyme-linked immunosorbent assay (ELISA) in order to investigate the reaction against the linear peptides generated. Two out of 58 synthetic 9-mers were strongly recognized by MS patients' antibodies compared to controls. A competitive inhibition assay demonstrated that these two epitopes are immunodominant antibody targets within MAP2694 protein, as sera pre-adsorbed with these peptides were able to significantly block the antibody reaction to the MAP2694 protein, even if at a lesser extent than MAP2694 protein itself.

Multiple sclerosis (MS) is thought to be triggered by environmental factors acting on a genetic predisposition. Sardinians share a homogeneous genetic background and boast one of the highest MS prevalence worldwide. We investigated Epstein–Barr virus (EBV) antibody prevalence in Sardinian population by ELISA. Our results show a higher serum prevalence of EBNA-1 IgG in MS patients compared to healthy controls. Moreover, analyzing a subset of patients treated for 6 months with IFN-β, we observed a decrease in their EBNA-1 specific IgG titers. These results confirm previous findings and strengthen the association between EBV and MS in Sardinia.

Introduction Les facteurs environnementaux impliques dans la pathogenese du diabete de type 1 (DT1) demeurent enigmatiques. Le Mycobacterium avium paratuberculosis (MAP) est transmis du betail laitier a l’homme par contamination des aliments. Le MAP provoque une infection asymptomatique qui est tres prevalente chez les patients DT1 par rapport aux sujets DT2 et sains de Sardaigne, une region qui affiche une incidence de DT1 parmi les plus hautes au monde. De plus, le MAP induit une reponse anticorpale contre plusieurs proteines mycobacteriennes. Patients et methodes Une de ces proteines, nommee MAP3865c, montre une homologie de sequence avec la proteine β-cellulaire transporteur de zinc 8 (ZnT8). Nous avons donc recherche si les anticorps (Acs) diriges contre MAP3865c pouvaient reconnaitre de facon croisee les epitopes peptidiques ZnT8 correspondants. A cette fin, les Acs anti-MAP386c ont ete mesures chez des sujets sardes DT1, DT2 et sains a l’aide d’un test Elisa. Resultats Les Acs anti-MAP3865c reconnaissent deux epitopes immuno-dominants dans 52–65 % des patients DT1, mais seulement dans 5–7 % des DT2 et 3–5 % des sains. Il y a une correlation lineaire entre les titres des Acs anti-MAP3865c et les titres des anti-ZnT8 qui ciblent les deux epitopes homologues. L’adsorption des serums par les epitopes ZnT8 inhibe la liaison aux epitopes MAP3865c correspondants. Conclusion Les Acs reconnaissant des epitopes MAP3865c presentent une reactivite croisee avec ZnT8. Cette reactivite croisee pourrait declencher un mecanisme de mimetisme moleculaire accelerant le DT1 chez des individus infectes par le MAP