Fulminant autoimmune Type 1 diabetes during interferon-alpha therapy: a case of Th1-mediated disease?
OBJECTIVE
A case of autoimmune Type 1 diabetes with some unique characteristics developing in a 29-year-old male during treatment with interferon-alpha (IFN-alpha) for chronic hepatitis C virus (HCV) hepatitis is reported.


METHODS
In this patient IFN-alpha treatment was well tolerated and successful in the cure of hepatitis with eradication of HCV infection within 3 months, but at 8.5 months Type 1 diabetes appeared and insulin therapy was started and maintained thereafter. HLA class II molecular typing was determined and retrospective measurement of islet cell (ICA), glutamate decarboxylase (GADA), tyrosin phosphatase IA-2 (IA-2A) and insulin (IAA) antibodies was performed in serum samples obtained before and at 0.5, 1, 2, 3, 4, 5, 6, 8.5, 10 and 13 months after the beginning of IFN-alpha treatment.


RESULTS
Complete HLA class II typing was consistent with homozygosity for the HLA DRB *03011, DQA1 *0501, DQB1 *0201 haplotype. All autoantibodies were undetectable prior to IFN-alpha therapy and remained undetectable up to 6 months of treatment; at 8.5 months, at the time of diabetes onset, ICA were detectable at low titre while GADA were present at high titre. Both ICA and GADA persisted at high levels in subsequent samples. IA-2A remained undetectable in all serum samples, while IAA appeared only after treatment with exogenous insulin.


CONCLUSIONS
This appears to be a case of autoimmune Type 1 diabetes induced by IFN-alpha treatment and developing on a predisposed genetic background with an unusually rapid development of the autoimmune process as reflected by the absence of detectable autoantibodies up to 2.5 months prior to disease onset. In this example of fulminant Type 1 diabetes a pathogenic process unbalanced towards a Th1-mediated autoimmune response is hypothesized. Diabet. Med. 18, 329-332 (2001)
Bosi
E
E
Department of Medicine, San Raffaele Hospital Scientific Institute, University of Milan, Milan, Italy. bosi.emanuele@hsr.it
Minelli
R
R
Bazzigaluppi
E
E
Salvi
M
M
D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects*; D001323:Autoantibodies / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D005802:Genes, MHC Class II; D005968:Glutamate Decarboxylase / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D000949:Histocompatibility Antigens Class II / Q000097:blood; D006650:Histocompatibility Testing; D006720:Homozygote; D006801:Humans; D007330:Insulin Antibodies / Q000097:blood; D016898:Interferon-alpha / Q000009:adverse effects*; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D018417:Th1 Cells / Q000276:immunology*; D013997:Time Factors
D000998:Antiviral Agents; D001323:Autoantibodies; D000949:Histocompatibility Antigens Class II; C096322:ICA512 autoantibody; D007330:Insulin Antibodies; D016898:Interferon-alpha; C024211:islet cell antibody; D005968:Glutamate Decarboxylase