The complement system in type 1 (insulin-dependent) diabetes.
The complement proteins C1q, r, s, C2, C4, C3, factor B, C5, C6, and the inhibitors, C1 inhibitors, factors I and H were measured in 35 patients with recently diagnosed Type 1 (insulin-dependent) diabetes, 76 patients with longer-duration disease (30 with complications) and 43 first-degree healthy relatives. We found that C1q, C4 and C3 were reduced significantly in all groups of patients (p less than 0.001 for each protein in recent onset and uncomplicated patients; p less than 0.01, p less than 0.01 and p less than 0.05 respectively, for patients with complications) compared to 60 control subjects and that C4 was also reduced in healthy relatives (p less than 0.001). C4 allotypes were examined in 63 subjects (selected from the patient groups) in order to clarify the role of null alleles in the production of the C4 abnormality. These showed serum C4 to be reduced significantly in 50 patients without null alleles (patient mean 0.24 g/l; control subject mean 0.34 g/l) (p less than 0.0001), although levels were lowest in the 13 patients with one or more null alleles (mean 0.19 g/l). Finally, to examine the metabolic basis for the low concentrations of C4 and C3, the turnover of highly-purified, radiolabelled C4 and C3 was measured in seven recently diagnosed patients; four of these had low levels of C4. The data showed that three out of four of these patients had reduced synthesis of C3 and C4 and normal values for fractional catabolic rate. Two patients showed features of C4 hypercatabolism. We conclude that several early complement proteins are reduced in Type 1 diabetes, irrespective of duration or complications.(ABSTRACT TRUNCATED AT 250 WORDS)
Charlesworth
J A
JA
Department of Medicine, Prince Henry Hospital, Sydney, Australia.
Timmermans
V
V
Golding
J
J
Campbell
L V
LV
Peake
P W
PW
Pussell
B A
BA
Wakefield
D
D
Howard
N
N
D000293:Adolescent; D000328:Adult; D000936:Antigen-Antibody Complex / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D003167:Complement Activation; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000032:analysis*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006207:Half-Life; D006801:Humans; D008297:Male
D000936:Antigen-Antibody Complex; D001786:Blood Glucose; D003165:Complement System Proteins; D006442:Glycated Hemoglobin