A bovine albumin peptide as a possible trigger of insulin-dependent diabetes mellitus.
BACKGROUND
Cow's milk has been implicated as a possible trigger of the autoimmune response that destroys pancreatic beta cells in genetically susceptible hosts, thus causing diabetes mellitus. Studies in animals have suggested that bovine serum albumin (BSA) is the milk protein responsible, and an albumin peptide containing 17 amino acids (ABBOS) may be the reactive epitope. Antibodies to this peptide react with p69, a beta-cell surface protein that may represent the target antigen for milk-induced beta-cell--specific immunity.


METHODS
We used immunoassays and Western blot analysis to analyze anti-BSA antibodies in the serum of 142 children with insulin-dependent diabetes mellitus, 79 healthy children, and 300 adult blood donors. Anti-ABBOS antibodies were measured in 44 diabetic patients at the time of diagnosis, three to four months later, and one to two years later.


RESULTS
All the diabetic patients had elevated serum concentrations of IgG anti-BSA antibodies (but not of antibodies to other milk proteins), the bulk of which were specific for ABBOS: The mean (+/- SE) concentration was 8.5 +/- 0.2 kilofluorescence units (kfU) per microliter, as compared with 1.3 +/- 0.1 kfU per microliter in the healthy children. IgA antibodies were elevated as well, but not IgM antibodies. The antibody concentrations declined after diagnosis, reaching normal levels in most patients within one to two years. The initial decline involved anti-ABBOS--specific antibodies almost exclusively. Much lower serum concentrations of anti-BSA antibodies were found in all 379 control subjects, but only 2.5 percent of them had small amounts of ABBOS-specific IgG.


CONCLUSIONS
Patients with insulin-dependent diabetes mellitus have immunity to cow's-milk albumin, with antibodies to an albumin peptide that are capable of reacting with a beta-cell--specific surface protein. Such antibodies could participate in the development of islet dysfunction.
Karjalainen
J
J
Hospital for Sick Children, Department of Pediatrics and Immunology, University of Toronto, ON, Canada.
Martin
J M
JM
Knip
M
M
Ilonen
J
J
Robinson
B H
BH
Savilahti
E
E
Akerblom
H K
HK
Dosch
H M
HM
D000906:Antibodies / Q000032:analysis*; D000918:Antibody Specificity; D001327:Autoimmune Diseases / Q000209:etiology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology; D000939:Epitopes; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D010446:Peptide Fragments / Q000276:immunology*; D012710:Serum Albumin, Bovine / Q000276:immunology*
D000906:Antibodies; D000939:Epitopes; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010446:Peptide Fragments; C075490:serum albumin, bovine (152-168); D012710:Serum Albumin, Bovine