Lack of predictive value of islet cell antibodies, insulin antibodies, and HLA-DR phenotype for remission in cyclosporin-treated IDDM patients. The Canadian-European Randomized Control Trial Group.
The effect of immunosuppression on the humoral immune response to islet autoantigens and exogenously administered insulin and the predictive value of islet cell cytoplasmic antibodies (ICAs), insulin antibodies (IAs), and HLA-DR phenotype for remission during immunosuppression were studied in a prospective randomized double-blind trial of cyclosporin administration in 98 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients. HLA-DR phenotype and glycosylated hemoglobin were determined at study entry, and insulin requirement, glucagon-stimulated C-peptide, ICAs, and IAs were measured at entry and after 1, 3, 6, 9, and 12 mo of follow-up. Cyclosporin therapy caused significant suppression of the prevalence and serum concentrations of ICAs and IAs. Cyclosporin-treated IDDM patients ICA+ at study entry had higher levels of stimulated C-peptide after 1 mo of study, but the increased beta-cell function was not associated with a higher frequency of insulin-free remission at 1 mo. ICA and IA status at entry did not predict cyclosporin-insulin-free remission as assessed by the prevalence of insulin-free remission or beta-cell function at 3-12 mo of study, and significant decrements in the titers or total disappearance of ICAs were not associated with an increased prevalence or duration of non-insulin-requiring remission or higher stimulated C-peptide values. There was no correlation between the serum levels of ICAs and IAs at entry and beta-cell function at 12 mo of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
Mandrup-Poulsen
T
T
Steno Memorial Hospital, Gentofte, Denmark.
Mølvig
J
J
Andersen
H U
HU
Helqvist
S
S
Spinas
G A
GA
Munck
M
M
D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D003524:Cyclosporins / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000453:epidemiology* / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D007165:Immunosuppression Therapy; D007330:Insulin Antibodies / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010641:Phenotype; D011237:Predictive Value of Tests; D011446:Prospective Studies
D001323:Autoantibodies; D003524:Cyclosporins; D006684:HLA-DR Antigens; D007330:Insulin Antibodies; C024211:islet cell antibody