Diet‐derived Xeno‐autoantigen Sialic acid Promotes Inflammation ‐ Evidence for “Xenosialitis”

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Sialic acids are monosaccharides with a 9‐carbon backbone and are terminating units of glycoconjugates that coat the vertebrate cell surface. The two major types are N‐acetylneuraminic acid (Neu5Ac) and its hydroxylated form, N‐glycolylneuraminic acid (Neu5Gc). Although Neu5Gc is deficient in humans, it is incorporated into tissues from diet, the first example of a “xeno‐autoantigen”. Given that occurs in the face of circulating anti‐Neu5Gc antibodies in humans, we hypothesized that this generates an antibody‐antigen reaction and inflammation known as “xenosialitis”. Anti‐Neu5Gc antibodies were generated by immunizing human‐like Cmah null mice with chimpanzee red blood cell ghosts and then passively transferred into Cmah null mice that were on a diet either with or without Neu5Gc. We showed incorporation of Neu5Gc into tissues by immunofluorescence and showed that mice fed with Neu5Gc and injected with anti‐Neu5Gc antibodies showed elevated levels of IL‐6 in the peritoneal fluid and higher levels of acute phase proteins in the serum as compared to controls. We also developed a new DMB‐HPLC method to quantitate the free and bound Neu5Gc in common foods and confirmed previous data that Neu5Gc is indeed enriched in red meats. In humans this possibly contributes to chronic inflammatory processes in diseases epidemiologically associated with red meat consumption, such as atherosclerosis and carcinomas.