Glycopolymers from Saccharomyces Cerevisiae BIM Y-195 with Unusual Immunochemical Properties: Isolation, Structural Identification and Prediction of Their Role in Pathogenesis/Treatment of Autoimmune Thyroid Diseases

Abstract

Molecular mimicry in the broad sense is structural, functional or immunologic similarity between unrelated macromolecules (Oldstone, 1998). In biomedical studies this phenomenon is discussed as the most proven mechanism of triggering/prevention of autoimmune diseases (Kivity et al., 2009). In this paper, we isolate and structurally identify the yeast biopolymers (BPs) that selectively bind human autoantibodies to thyroid peroxidase (TPO) and thyroglobulin (Tg) (anti-TPO and anti-Tg, respectively), e.g. immunologically mimic thyroid antigens. The BPs, viz., BPanti-TPO and BPanti-Tg, were isolated from the soluble fraction of S. cerevisiae BIM Y-195 by affinity chromatography with anti-TPO or anti-Tg, respectively. Both affinity eluates, AEanti-TPO and AEanti-Tg, showed functional activity characteristic of BPanti-TPO and BPanti-Tg, viz, ability (i) to distinquish anti-TPO (anti-Tg) from other IgG and (ii) to compete with TPO (Tg) for binding of anti-TPO (anti-Tg) in ELISA tests. The semi-preparative size exclusion chromatography of AEanti-TPO and AEanti-Tg with detection by refractometer gave a 5000-7000 Da fractions containing pure BPanti-TPO and BPanti-Tg, respectively, according to ELISA data. Analysis by two-dimensional NMR spectroscopy including 1 H, 1 H COSY and 1 H, 13 C HSQC experiments indicated that both substances are linear α-1, 6-glucans.