title: Differential reactivity to IMPDH2 by anti-rods/rings autoantibodies and unresponsiveness to pegylated interferon-alpha/ribavirin therapy in US and Italian HCV patients.
abstract: OBJECTIVE
  Autoantibodies to cytoplasmic structures called rods and rings (RR) are primarily specific to patients with hepatitis C virus (HCV) infection treated with pegylated interferon-alpha/ribavirin (IFN/R). Our aim is to examine anti-RR antibodies specificity and correlation with the response to IFN/R therapy in two independent cohorts (US and Italy) of HCV patients.
  
  
  METHODS
  Sera from the US cohort (n = 47) and the Italian cohort (n = 46) pre-selected for anti-RR antibodies were analyzed by immunofluorescence and radioimmunoprecipitation. The prevalence and titers of anti-RR were analyzed for correlation with the response to IFN/R therapy.
  
  
  RESULTS
  In the US cohort, anti-RR antibodies were more frequently non-responders to IFN/R (71 % vs 29 % responders). Titers in responder patients (n = 11) were ≤1:3200, whereas titers in non-responder patients (n = 27) reached 1:819,200 (p = 0.0016). In the Italian cohort, anti-RR titers ranged from 1:200 to >1:819,200 and only relapsers had the highest anti-RR titers. Radioimmunoprecipitation demonstrated that anti-RR autoantibodies were mainly anti-inosine monophosphate dehydrogenase 2 (IMPDH2) - 96 % in the Italian cohort vs. 53 % in the US cohort.
  
  
  CONCLUSIONS
  In the two cohorts analyzed, the anti-IMPDH2 response as a component of the anti-RR response is much more prominent in the Italian cohort. The reason for the difference between the US and Italian cohorts is unclear but it possibly illustrates the heterogeneity in response and the overall negative correlation between the production of these autoantibodies and response to IFN/R therapy. Patients with high titer anti-RR antibodies are either relapsers (Italian) or non-responders/relapsers (US).
authors.affiliation: Department of Oral Biology, University of Florida, Gainesville, FL 32610-0424, USA.
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Carcamo
authors.forename: Angela
authors.initials: A
authors.lastname: Ceribelli
authors.forename: S John
authors.initials: SJ
authors.lastname: Calise
authors.forename: Claire
authors.initials: C
authors.lastname: Krueger
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Massimo
authors.initials: M
authors.lastname: Daves
authors.forename: Danilo
authors.initials: D
authors.lastname: Villalta
authors.forename: Nicola
authors.initials: N
authors.lastname: Bizzaro
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Edward K L
authors.initials: EK
authors.lastname: Chan
mesh_terms: D000918:Antibody Specificity; D000998:Antiviral Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015331:Cohort Studies; D006526:Hepatitis C / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D007168:IMP Dehydrogenase / Q000276:immunology*; D016898:Interferon-alpha / Q000627:therapeutic use*; D007558:Italy; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D016036:Seroepidemiologic Studies; D016896:Treatment Outcome; D014481:United States
chemical_list: D000998:Antiviral Agents; D001323:Autoantibodies; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D007168:IMP Dehydrogenase; C501687:IMPDH2 protein, human; C100416:peginterferon alfa-2a