Journal of Cellular Biochemistry 89:301–310 (2003) Developmental Expression of the Type I Diabetes Related Antigen Sulfatide and Sulfated Lactosylceramide in Mammalian Pancreas Maria Blomqvist, 1 * Anne Kaas, 2 Jan-Eric Ma ˚nsson, 1 Bent Formby, 3 Britt-Marie Rynmark, 1 Karsten Buschard, 2 and Pam Fredman 1 1 Institute of Clinical Neuroscience, Experimental Neuroscience Section, The Sahlgrenska Academy at Go ¨ teborg University, Sahlgrenska University Hospital/Mo ¨ lndal, SE-431 80 Mo ¨ lndal, Sweden 2 Bartholin Instituttet, Kommunehospitalet, DK-1399 Copenhagen K, Denmark 3 The Rasmus Institute for Medical Research, Santa Barbara, California 93105 Abstract Previous studies have shown that sulfatide is present and functionally involved in beta cells, and that anti- sulfatide antibodies (ASA) exist during development of type I diabetes mellitus. To further explore the possible role of sulfatide in type I diabetes, developmental expression was examined in human pancreas and in pancreas of the type I diabetes models BB rat and NOD mouse compared to Lewis rat and BALB/c mouse, respectively. Sulfatide was not only expressed in adult pancreas, but also in human fetal and rodent neonatal pancreas, i.e., during the growing period of the immunological self. Sulfatide had a different expression pattern in human beings and rodents, concerning both the amounts of sulfatide and expression during development. There was no change in the sulfatide fatty acid isoform expression during development. The pancreatic expression of another sulfated glycosphingolipid, sulfated lactosylcer- amide, indicated that this molecule is a potential fetal/neonatal marker, which was further expressed in the type I diabetic models. In conclusion, these findings give further support to the possibility that sulfatide is a relevant autoantigen in type I diabetes and that sulfated lactosylceramide might function as a potential risk factor for disease development, at least in the animal models. J. Cell. Biochem. 89: 301 – 310, 2003. ß 2003 Wiley-Liss, Inc. Key words: sulfatide; sulfated lactosylceramide; glycosphingolipid; type I diabetes mellitus; animal model; fetal; neonatal Sulfatide is known as a neuronal epitope present in large amounts in the central and peripheral nervous system mainly located to the myelin [Vos et al., 1994], where it has been found to be of importance for the maintenance of the structure and function of the myelin sheet [Coetzee et al., 1996]. The association of type I (insulin dependent) diabetes mellitus with the Stiff-man syndrome [Baekkeskov et al., 1990], and possibly with Guillian-Barre ´ syndrome [Rabinowe, 1990], and the findings of paresis and diabetes in the encephalomyocarditis virus mouse model [Buschard, 1985], suggest the occurrence of a common antigen between endo- crine pancreas and nerve tissue. Sulfatide has been investigated as one plausible candidate antigen. Sulfatide is present in the plasma membrane and in secretory granules of pan- creatic beta cells [Buschard et al., 1993b] and anti-sulfatide antibodies (ASA) are found in patients with newly diagnosed type I diabetes [Buschard et al., 1993a]. ASA was also found in ß 2003 Wiley-Liss, Inc. Abbreviations used: C/M/W, chloroform/methanol/water; ESI-MS, electrospray ionization-mass spectrometry; TLC- ELISA, thin-layer chromatography-enzyme linked immuno- sorbant assay; ASA, anti-sulfatide antibodies; CST, cerebro- side sulfotransferase. Grant sponsor: Swedish Medical Research Council; Grant number: K2000-03X-09909-09A; Grant sponsor: A þ Science Invest; Grant sponsor: Swedish Foundation for Strategic Research (Glycoconjugates in Biological Systems Program). *Correspondence to: Maria Blomqvist, Institute of Clinical Neuroscience, Experimental Neuroscience Section, The Sahlgrenska Academy at Go ¨teborg University, Sahl- grenska University Hospital/Mo ¨lndal, SE-431 80 Mo ¨lndal, Sweden. E-mail: maria.blomqvist@neuro.gu.se Received 12 November 2002; Accepted 29 January 2003 DOI 10.1002/jcb.10513