Humoral immunity in type 1 diabetes mellitus: a prospective study

Cytoplasmic islet cell antibodies, as detected by anti-IgG (ICAb), and circulating immune complexes (AgAb), detected by the solid phase C1q test (C1qSP), were evaluated in 153 insulin dependent diabetics (IDD) at diagnosis and subsequently in 88 of these patients who were studied prospectively at regular intervals for up to 3 yr. AgAb detected by the conglutinin (KgBt) and Raji cell (RAJI) techniques were also studied at diagnosis in 34 and 50 diabetics respectively. Normal controls were included in the AgAb studies. Complement fixing islet cell antibodies (CF-ICAb) were evaluated in 30 randomly selected diabetics both at diagnosis and after 6 months. Viral antibodies (VAb) were measured in 30 IDD at diagnosis and in 30 matched controls. Insulin antibodies (IBC) were measured 9 months after diagnosis in 35 diabetics and HLA studies (B8 and B15) performed in 115 patients. In the prospective study the ICAb positivity declined from 50% at diagnosis to 45, 38, 36, 31, 26, 19 and 17% at 1, 3, 6, 9, 12, 24 and 36 months after diagnosis respectively. CF-ICAb were found in 30% of the diabetics at diagnosis and in 23% at 6 months. All patients with CF-ICAb at diagnosis were ICAb positive whilst only 47% of patients with ICAb also had CF-ICAb in the serum. AgAb were found at diagnosis in 35% of patients by C1qSP (p less than 0.001 vs. normals), in 35% by KgBt (p less than 0.001) and in 54% by RAJI (p less than 0.002). Eighty-four patients were studied at diagnosis by more than one AgAb method and of these 57% had at least one positive AgAb result. AgAb by C1qSP declined to less than 20% within 6 months of diagnosis. AgAb, as measured by C1qSP and RAJI techniques, correlated with ICAb at diagnosis whereas there was no correlation with VAb levels, IBC values, nor with the HLA antigens. There was no correlation between AgAb (C1q) and CF-ICAb. HLA B15 positive patients tended to form higher IBC levels than B15 negative patients. Thus, AgAb presence seems to parallel that of ICAb in the early stages of diabetes and both phenomena may be primarily or secondarily involved in the development of the disease.