Fulminant autoimmune Type 1 diabetes during interferon-alpha therapy: a case of Th1-mediated disease?

AIM: 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. PATIENT AND 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. DISCUSSION: 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)