DIETARY TRIGGERS OF IDDM

Abstract

Higher incidence of IDDM was reported in children exposed to cow milk early in life vs. those breastfed for longer periods. Spontaneously IDDM rodents are also protected by elimination of cow milk proteins (Prot) in the diet, mainly β-lactoglobulin (LG) and bovine serum albumin (BSA), when such restriction occurs at weaning. We found that antibodies (Ab) to BSA (but not to LG) cross react with a BB-rat islet cell membrane prot. (Mr=69Kd) as demonstrated by Western blotting and by Fluorography when extracted radioactive labelled islet-cell prot. were immunoprecipitated and separated by gel-electrophoresis. The precipitate increased in cells pre-exposed to interferon-γ. Comparative aa. sequences of human, rat and bovine SA. showed clear differences in the latter vs. the others between residues 138-166, which could-serve as epitopes. Overlapping this region (aa.157-175) is a homologous area between BSA and the primary structure of β-subunits of prot. Ia, and DQ and DR (aa.50-79). Corresponding to aa-57 of DQ antigens, human albumin has an Asp. residue while BSA has an Ala. Similar substitutions occur in the Ia-β prot. of IDDM mice and rats vs. normal controls. Hypothesis: Absorption of milk BSA early in life triggers an immune response by Ab. that cross-react with MHC Class II antigens as a typical “mimicry” event.