
Autoantibodies to glucosylated proteins in the plasma of patients with diabetes mellitus.
Author(s) -
J L Witztum,
U P Steinbrecher,
Kesäniemi Ya,
Milton Fisher
Publication year - 1984
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.81.10.3204
Subject(s) - immunogen , autoantibody , diabetes mellitus , antibody , blood proteins , immune system , medicine , chemistry , endocrinology , low density lipoprotein , lipoprotein , epitope , biochemistry , immunology , cholesterol , monoclonal antibody
Nonenzymatic glucosylation interferes with recognition of low density lipoprotein (LDL) by its receptor and markedly decreases the rate of plasma clearance of glucosylated LDL, both in experimental animals and in normal human subjects. However, in selected diabetic subjects we have observed a paradoxical increase in the clearance of glucosylated LDL, suggesting the possibility of immune-mediated clearance. Immunoassay demonstrated antibodies specific for glucosylated LDL in the preinjection plasma of each of four such diabetic subjects studied. These antibodies cross-react with other glucosylated proteins and recognize specifically the glucosylated lysine epitope--i.e., glucitollysine . These data suggest that nonenzymatic glucosylation of plasma or structural proteins may render them immunogenic and result in production of autoantibodies that recognize not only the particular immunogen but also many other glucosylated proteins, including glucosylated tissue proteins. These findings may be relevant to the increased prevalence of immune complexes in plasma of diabetic subjects and the late complications of diabetes mellitus.