Phylogenetic Distribution of CMP-Neu5Ac Hydroxylase (CMAH), the Enzyme Synthetizing the Proinflammatory Human Xenoantigen Neu5Gc

Peri, Sateesh; Kulkarni, Asmita; Feyertag, Felix; Berninsone, Patricia M; Alvarez-Ponce, David

Inactivation of CMAH in humans meant that Neu5Gc became a foreign antigen. Neu5Gc from animal foods (predominantly red meats and milk products; Tangvoranuntakul et al. 2003; Samraj et al. 2015) is incorporated into the glycoproteins of human tissues (Tangvoranuntakul et al. 2003; Bardor et al. 2005; Banda et al. 2012) , where it is thought to elicit an immune response that may result in chronic inflammation, rheumatism, and cancer (Varki and Varki 2007) . This may explain, at least in part, the link between red meat consumption and cancer (Rose et al. 1986; Giovannucci et al. 1993; Fraser 1999; Tavani et al. 2000; Willett 2000; Linseisen et al. 2002; Bosetti et al. 2004; Zhang and Kesteloot 2005; Tseng et al. 2015) . In support of this hypothesis, Neu5Gc often concentrates in human tumors and sites of inflammation (Malykh et al. 2001; Tangvoranuntakul et al. 2003; Diaz et al. 2009 ), and CMAH À/À mice develop systemic inflammation and a high frequency of cancer when fed with bioavailable Neu5Gc (Samraj et al. 2015) .