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The clinical relevance of persistent recombinant immunoblot assay–indeterminate reactions: insights into the natural history of hepatitis C virus infection and implications for donor counseling
Author(s) -
Makuria Addisalem T.,
Raghuraman Sukanya,
Burbelo Peter D.,
Cantilena Cathy C.,
Allison Robert D.,
Gibble Joan,
Rehermann Barbara,
Alter Harvey J.
Publication year - 2012
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2011.03524.x
Subject(s) - indeterminate , medicine , serology , immunology , antibody , clinical significance , hepatitis c virus , viral disease , context (archaeology) , virus , antigen , virology , biology , paleontology , mathematics , pure mathematics
BACKGROUND: Recombinant immunoblot assay (RIBA) is used to determine the specificity of antibody to hepatitis C virus (anti‐HCV). The RIBA result is recorded as positive, negative, or indeterminate. The interpretation and significance of RIBA‐indeterminate reactions are unclear. We addressed the clinical relevance of these reactions in the context of the natural history of HCV infection in a prospectively followed cohort of anti‐HCV–positive blood donors. STUDY DESIGN AND METHODS: Donor demographics, exposure history, and humoral and cell‐mediated immunity (CMI) were compared in 15 RIBA‐indeterminate subjects, nine chronic HCV carriers, and eight spontaneously recovered subjects. Serum samples were tested for anti‐HCV by a quantitative, liquid luciferase immunoprecipitation system (LIPS). CMI was assessed by interferon‐γ enzyme‐linked immunosorbent spot assay. RESULTS: In the LIPS assay, the sum of antibody responses to six HCV antigens showed significant (p < 0.001) stepwise diminution progressing from chronic carriers to spontaneously recovered to RIBA‐indeterminate subjects. CMI responses in RIBA‐indeterminate subjects were similar to spontaneously recovered subjects and greater than chronic carriers and controls (p < 0.008). A parenteral risk factor was identified in only 13% of RIBA‐indeterminate subjects compared to 89% of chronic carriers and 87% of spontaneously recovered subjects. RIBA‐indeterminate donors were older than the other groups. CONCLUSION: The CMI and LIPS results suggest that persistent RIBA‐indeterminate reactions represent waning anti‐HCV responses in persons who have recovered from a remote HCV infection. In such cases, detectable antibody may ultimately disappear leaving no residual serologic evidence of prior HCV infection, as reported in a minority of long‐term HCV‐recovered subjects.