Low serum haemolytic function of the fourth complement component (C4) in insulin dependent diabetes.

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Abstract
Low serum concentration of the fourth component of complement (C4) are found in insulin dependent diabetes, and may be important in the aetiology of the disease. To ascertain whether function of C4 is also impaired both its haemolytic activity and its concentration were measured in 34 insulin dependent diabetes, 15 non-insulin dependent diabetics, 20 healthy subjects, and 12 pairs of monozygotic twins discordant for insulin dependent diabetes. C4 function was measured by a radial immune haemolytic assay, and C4 concentration by laser nephelometry. Both measurements were significantly lower in insulin dependent diabetes (C4 function: median 47%, range 4-100%; C4 concentration: 0.22 g/l, 0.10-0.38 g/l) than in non-insulin dependent diabetics (67%, 138%, p < 0.01; 0.27 g/l, 0.16-0.50 g/l, p < 0.02) and controls (74%, 33-138%, p < 0.01; 0.27 g/l, 0.18-0.40 g/l, p < 0.03). C4 function and concentration were lower in both diabetic (48%, 12-100%; 0.17 g/l, 0.08-0.31 g/l) and non-diabetic twins (47%, 12-100%; 0.17 g/l, 0.07-0.36 g/l) than controls (p < 0.01). Thirteen (38%) of the insulin dependent diabetics had a reduction in either C4 function or concentration, but in only five were both features reduced. Values of function and concentration were strongly correlated in both diabetic and non-diabetic twins (r = 0.95, p < 0.001; r = 0.92, p < 0.001). These results below show defects in C4 function and concentration in insulin dependent diabetes, which-being present in the non-diabetic co-twin of diabetics-may represent a genetic predisposition to the disease.