Does non-enzymatic glycosylation affect complement function in diabetes?
We examined the role of non-enzymatic glycosylation in abnormalities of the complement system commonly found in Type 1 diabetes. Fourteen patients were found to have significantly increased levels of glycosylated C3 (p less than 0.001) and C4 (p less than 0.002) with levels of glycosylated C3 being higher than those of C4 (4.1 +/- 2.5% vs 0.8 +/- 0.8%). This correlated with the finding that in vitro, purified C3 was far more susceptible to this modification than C4. Autoradiography of limited trypsin digests of H3-glycosylated iC3 showed several sites were available for reaction. However, high levels of in vitro glycosylation had no significant effect on the haemolytic activity of C3 and C4, or the binding of iC3 to the CR1 receptor on erythrocytes. Further, IgG was similarly unaffected by non-enzymatic glycosylation in its ability to activate the complement pathway, or when present in an immune complex, to be dissociated from it by complement. We concluded that the immune complex-mediated damage implicated in some complications of Type 1 diabetes is unlikely to derive from any loss of complement function due to non-enzymatic glycosylation.
Peake
P W
PW
Division of Medicine, Prince Henry Hospital, Sydney, Australia.
Charlesworth
J A
JA
Timmermans
V
V
Gavrilovic
L
L
Pussell
B
B
D000936:Antigen-Antibody Complex; D001798:Blood Proteins / Q000302:isolation & purification; D003176:Complement C3 / Q000032:analysis* / Q000302:isolation & purification; D003165:Complement System Proteins / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D006023:Glycoproteins; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G; D011865:Radioisotope Dilution Technique; D012016:Reference Values; D014316:Tritium; D000093422:Glycated Serum Proteins
D000936:Antigen-Antibody Complex; D001798:Blood Proteins; D003176:Complement C3; D006023:Glycoproteins; D007074:Immunoglobulin G; D014316:Tritium; D003165:Complement System Proteins; D000093422:Glycated Serum Proteins