IDF (2000)

MARKERS OF DESTRUCTION OF  beta-cellS AND APOPTOTIC LYMPHOCYTES PRECOMITATION IN IDDM PATIENTS
T.V. Mokhort, S.B. Melnov, and V.A. Goranov

It was established, that the reduction of internal ability to eliminate the specific autoreactive lymphocytes from the patients with IDDM promotes the immunologic reactivity preservation against beta-cells.
The main consequents of this process are the aggravation of clinical disease manifestation, the rising of the in exogenous insulin and the risk of possible clinical complications. One of the main gears for the lymphocytes pool regulation is apoptosis. The published results confirm the hyperexpression bcl-2 in the lymphocytes of the patients with IDDM. On the other hand, the interrelation between antibeta-cells lymphocyte activity and the level of their apoptotic ”escape” is not clear enough yet.
Using the flow cytometry approach with FACS-vantage we investigated CD95-expression, levels of serum C-peptide and specific antibodies to beta-cells antigens (GAD65 and IA2) by immunoassays in patients with disease duration up to 3 years. Only  GAD65 and IA2 - positive patients have been included in following analysis. Group under investigation includes 20 patients and control group - 8 person.
It was found that the reduction of CD95 expression practically in 2 times - 8.5±4.5 (control level - 16.4±3.1%). This confirms the reduction of the FAS-dependent apoptotic pathway. We differentiated 12 persons with the level of residual secretion of C-peptide exceeded the 154 pM level. This group had statistically reliable negative correlation (r=-0.85) between the levels CD95 expression and antibodies to beta-cells antigens. In the serum of the patients of the rest group the C-peptide concentrations were under 145 pM.
The violation of the normal apoptotic lymphocyte elimination in some situation is able to facilitate to high activity of immune system against  beta-cells. But, it is impossible to exclude the role of the alternative mechanisms of beta-cells destruction in this situation.