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.
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.


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.


CONCLUSIONS
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.
Infectious Disease Section, Department of Transfusion Medicine, National Institute for Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Addisalem T
AT
Makuria
Sukanya
S
Raghuraman
Peter D
PD
Burbelo
Cathy C
CC
Cantilena
Robert D
RD
Allison
Joan
J
Gibble
Barbara
B
Rehermann
Harvey J
HJ
Alter
D000328:Adult; D000937:Antigen-Antibody Reactions / Q000502:physiology; D058070:Asymptomatic Diseases / Q000453:epidemiology / Q000628:therapy; D001782:Blood Donors / Q000706:statistics & numerical data; D003937:Diagnosis, Differential; D037001:Directive Counseling / Q000706:statistics & numerical data*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000276:immunology* / Q000302:isolation & purification; D006526:Hepatitis C / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000032:analysis / Q000097:blood*; D006801:Humans; D015151:Immunoblotting / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012189:Retrospective Studies
D018937:Hepatitis C Antibodies; D011994:Recombinant Proteins