IA-2 antibody-negative status predicts remission and recovery of C-peptide levels in type 1 diabetic patients treated with cyclosporin.
OBJECTIVE
The use of cyclosporin in recent-onset type 1 diabetes has demonstrated the potential for immune intervention in the treatment and prevention of the disease. However, a proportion of patients failed to respond to cyclosporin treatment. Indicators of resistance to immune intervention would be valuable for the most effective use of such therapies in disease prevention. The aim of this study was to determine whether presence of IA-2 antibodies is such a marker.


METHODS
IA-2 antibodies were determined by radioligand binding assay in sera from patients recruited into the Canadian-European cyclosporin trial. Insulin dose requirements and glucagon-stimulated C-peptide secretion were analyzed in patients grouped according to IA-2 antibody status at entry.


RESULTS
Cyclosporin treatment had no significant effect on frequency of IA-2 antibodies during the 1 year of treatment. Cyclosporin caused significant reduction in insulin requirements and significant increases in C-peptide secretion mainly in patients negative for IA-2 antibodies. Analysis of GAD antibodies in combination with antibodies to IA-2 indicated that the group most resistant to cyclosporin were IA-2 antibody positive, GAD antibody negative.


CONCLUSIONS
The results demonstrate that IA-2 antibody analysis is valuable in identifying individuals for whom immunosuppressive treatment would be most effective.
Christie
Michael R
MR
Department of Medicine, Guy's, King's and St. Thomas' School of Medicine, London, UK. michael.christie@kcl.ac.uk
Mølvig
Jens
J
Hawkes
Charlotte J
CJ
Carstensen
Bendix
B
Mandrup-Poulsen
Thomas
T
D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D002096:C-Peptide / Q000097:blood*; D016572:Cyclosporine / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D010919:Placebos; D011237:Predictive Value of Tests; D013997:Time Factors
D001323:Autoantibodies; D002096:C-Peptide; D016572:Cyclosporine; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007166:Immunosuppressive Agents; D007328:Insulin; D010919:Placebos; C096322:ICA512 autoantibody