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 d eveloping in a 29-year-old male during treatment with interferon-alpha (IFN -a) 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 w ithin 3 months, but at 8.5 months Type 1 diabetes appeared and insulin ther apy was started and maintained thereafter. HLA class II molecular typing wa s determined and retrospective measurement of islet cell (ICA), glutamate d ecarboxylase (GADA), tyrosin phosphatase IA-2 (IA-1A) and insulin (IAA) ant ibodies 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-a treatment. Results Complete HLA class II typing was consistent with homozygosity for t he HLA DRB *03011, DQA1 *0501, DQB1 *0201 haplotype. All autoantibodies wer e undetectable prior to IFN-a therapy and remained undetectable up to 6 mon ths of treatment; at 8.5 months, at the time of diabetes onset, ICA were de tectable at low titre while GADA were present at high titre. Both ICA and G ADA persisted at high levels in subsequent samples. IA-2A remained undetect able in all serum samples, while IAA appeared only after treatment with exo genous insulin. Discussion This appears to be a case of autoimmune Type 1 diabetes induced by IFN-a treatment and developing on a predisposed genetic background with an unusually rapid development of the autoimmune process as reflected by th e absence of detectable autoantibodies up to 2.5 months prior to disease on set. In this example of fulminant Type 1 diabetes a pathogenic process unba lanced towards a Th1-mediated autoimmune response is hypothesized.