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Journal of Clinical Immunology

, Volume 33, Issue 2, pp 420–426 | Cite as

Differential Reactivity to IMPDH2 by Anti-rods/rings Autoantibodies and Unresponsiveness to Pegylated Interferon-alpha/Ribavirin Therapy in US and Italian HCV Patients

  • Wendy C. Carcamo
  • Angela Ceribelli
  • S. John Calise
  • Claire Krueger
  • Chen Liu
  • Massimo Daves
  • Danilo Villalta
  • Nicola Bizzaro
  • Minoru Satoh
  • Edward K. L. Chan
Original Research

Abstract

Purpose

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).

Keywords

IMPDH2 hepatitis C autoantibody 

Abbreviations

ANA

Anti-nuclear antibody

CTPS1

Cytidine triphosphate synthetase 1

DON

6-diazo-5-oxo-L-norleucine

HCV

Hepatitis C virus

IFN/R

Pegylated interferon-alpha/ribavirin

IFN-α

Pegylated interferon-alpha

IIF

Indirect immunofluorescence

IMPDH2

Inosine monophosphate dehydrogenase 2

IP

Immunoprecipitation

NR

Non-responders

RBV

Ribavirin

RR

Rods and rings

SVR

Sustained virological response

Notes

Acknowledgements

Natasha Deming, Pabina Dhawan, and Jennifer R. Bess are acknowledged for the early work helping in the screening of HCV patient sera for anti-RR positive samples.

Disclosures

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Wendy C. Carcamo
    • 1
  • Angela Ceribelli
    • 1
  • S. John Calise
    • 1
  • Claire Krueger
    • 1
  • Chen Liu
    • 2
  • Massimo Daves
    • 3
  • Danilo Villalta
    • 4
  • Nicola Bizzaro
    • 5
  • Minoru Satoh
    • 2
    • 6
  • Edward K. L. Chan
    • 1
  1. 1.Department of Oral BiologyUniversity of FloridaGainesvilleUSA
  2. 2.Pathology, Immunology, and Laboratory MedicineUniversity of FloridaGainesvilleUSA
  3. 3.Clinical BiochemistryGeneral HospitalBolzanoItaly
  4. 4.Allergology and Clinical ImmunologyA.O. S. Maria degli AngeliPordenoneItaly
  5. 5.Laboratory of Clinical PathologySan Antonio HospitalTolmezzoItaly
  6. 6.Division of Rheumatology and Clinical Immunology, Department of MedicineUniversity of FloridaGainesvilleUSA

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