Evidence of delayed ?-cell destruction in Type 1 (insulin-dependent) diabetic patients with persisting complement-fixing cytoplasmic islet cell antibodies

Abstract

Summary. Forty-four children with Type 1 (insulin-dependent) diabetes (aged 0.7-16.7 years) were observed from diagnosis for cytoplasmic islet cell antibodies and serum C-peptide concentrations. Islet cell antibodies were analysed by indirect immunofluorescence for both conventional IgG and complement-fixing antibodies. Thirty-seven children (84%) were found to be positive for conventional islet cell antibodies at diagnosis, and 21 (48%) remained positive over the observation period. Twenty-six patients (59%) were positive for complement-fixing antibodies at diagnosis and eight remained so during the follow-up period. The serum C-peptide concentrations increased significantly during the first 3 months after diagnosis, after which there was a gradual decrease in the levels. Those children who remained positive for complement-fixing antibodies over the observation period had significantly higher serum C-peptide concentrations on several occasions during the second year and had also a higher integrated serum C-peptide concentration over the initial 2 years than those who became negative for complement-fixing antibodies. These observations suggest that the continuous production of complement-fixing islet cell antibodies in those patients who are positive for these antibodies at diagnosis presupposes the preservation of a sufficient amount of functioning/~ cells for antigenic stimulation. These results support the view that the complement-fixing islet cell antibodies reflect ongoing destructive processes in the/3 cells.

Islet Cell Antibodies as Predictive Markers for IDDM in Children With High Background Incidence of Disease

“…The IF-ICA frequency in this study is 12 times and the CF-ICA frequency is 3 times higher than the prevalence of IDDM in this age-group in Finland, suggesting that a significant number of individuals were exposed to p-cell damage without progressing to IDDM. In our earlier studies, we showed the frequencies of both IF-ICAs and CF-ICAs among newly diagnosed IDDM children to be comparable with results obtained by other studies (38,39). In this survey, boys were overrepresented among CF-ICA + subjects, which is consistent with the higher incidence rates of IDDM among boys.…”

“…ICAs seem to be detectable in about the same proportion in the serums of newly diagnosed IDDM patients in various populations (8,11,19,38), supporting the pathogenetic homology of IDDM, whereas in first-degree relatives of diabetic patients, the prevalence of conventional ICAs has ranged from 1 to 10% of the individuals studied (28)(29)(30). In summarizing the ICA-frequency data in nondiabetic subjects from several cross-sectional studies published, 0-3.7% (mean 0.42%, 64/15,083 of nondiabetic subjects studied for ICA) were IF-ICA + .…”

Use of an islet cell antibody assay to identify type 1 diabetic patients with rapid decrease in C-peptide levels after clinical onset. Belgian Diabetes Registry.

“…The assay depends on the quality of the donor organ used, is difficult to standardize, and yields, at best, semiquantitive results (4,39). Interlaboratory differences in ICA technology and the use of small or selected patient groups are factors that may help explain previous conflicting reports on the relationship between ICA and C-peptide levels (18)(19)(20)(21)(22)(23)(24)(25)(26)(27). ICA are made up of a mix of autoantibodies with different specificities, including IA-2A and GADA.…”

Islet cell-specific autoantibodies in children with insulin-dependent diabetes mellitus and their siblings at clinical manifestation of the disease

“…We analysed 781 probands younger than 15 years of age for islet cell antibodies (ICA) and 755 for insulin autoantibodies (IAA) and 610 of their 3\p=n-\19-year-old non-diabetic siblings for ICA and IAA upon diagnosis of the proband. Conventional ICA have been found in diabetic children with a prevalence of 60-85% at diagnosis (3)(4)(5)(6)(7)(8), the frequency falling to about 30% after 5 years (3). The ICA-positive probands were younger in age and had higher IAA levels than the ICA-negative probands, while the IAA-positive probands were younger and had higher levels of ICA than the IAA-negative probands.…”