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!Multiple sclerosis is an autoimmune disease that affects the central nervous system. The key role of the glycosylation in disease pathogenesis has been previously studied and the synthetic Nglucosylated peptide CSF114(Glc) proved its efficiency in autoantibody recognition in the sera of multiple sclerosis patients. Herein, pure natural triterpene glycosides containing different glycosyl moieties were isolated and tested in multiple sclerosis patientsʼ sera to better understand the role of glycosylation. They were selected taking into account the nature and complexity of their osidic part. Five triterpene glycosides were isolated from several plants with more than 95% purity. The interaction between these glycosides and autoantibodies was evaluated in an enzyme-linked immunosorbent assay measuring IgG and IgM levels in multiple sclerosis patients and healthy blood donors, and the results were compared with those of CSF114(Glc). For each antigen, Mann Whitney and receiver operating characteristic-based analysis were performed to evaluate any statistical significance of the results. The five natural triterpene glycosides showed good capacity to recognize IgMs (sensitivity up to 38 %) with a high specificity (88.9%) for multiple sclerosis patients.Key words multiple sclerosis · triterpene glycosides · autoimmune disease · biomarkers · autoantibody recognition Supporting information available online at http://www.thieme-connect.de/products Complex glycoconjugates, including glycolipids and glycoproteins, are commonly displayed on cell surfaces, where they play crucial roles as intermediaries in extracellular communication and signalling networks [1][2][3]. Therefore, studies on glycan modification patterns of glycoconjugates are a great challenge in medical diagnostic research, offering insight into cellular molecular mechanisms. Moreover, glycoconjugates can be proposed as molecular biomarkers for the disease activity [4,5]. In the field of autoimmunity, different approaches are used to investigate the structures and functions of complex naturally occurring glycoconjugates leading to the identification of autoantigens associated with different autoimmune diseases. In particular, in the context of multiple sclerosis (MS), the development of serum antibodies as biomarkers to be used for the diagnosis, monitoring, and prognosis of such a heterogeneous disease is a challenge because of the ambiguous identification of antigens (Ags) implicated in the disease. MS pathogenesis has not been yet elucidated but includes viral, immunological, and vascular hypotheses [6]. Most of the putative Ags belong to the myelin protein family (i.e., myelin basic protein, proteolipid lipoprotein, and myelin oligodendrocyte glycoprotein). Moreover, pathophysiological post-translational modifications of native Ags can trigger the immune system to generate autoantibodies escaping conventional diagnostic procedures [7]. Thus, autoantibodies against aberrant glycosylations have been hypothesized as diagnostic biomarkers in MS [8,9]. I...