Influence of viraemia and genotype upon serological reactivity in screening assays for antibody to hepatitis C virus.
Detection of antibody to recombinant proteins derived from hepatitis C virus (HCV) genotype 1 represents the principal method for diagnosis of HCV infection. A method was developed for quantifying antibody reactivity in two third-generation enzyme immunoassays (Ortho EIA 3.0 and Murex VK48), and the influence of viraemia, HCV genotype, and host factors such as age, gender, and risk group upon antibody levels were investigated in a consecutive series of 117 anti-HCV-positive volunteer blood donors. Viraemic donors (as assessed by the polymerase chain reaction; PCR) showed significantly higher levels of anti-HCV by the Ortho EIA than those who were nonviraemic (adjusted mean difference of 10.1 fold after multiple regression analysis). The only other factor to influence significantly antibody level was genotype, where it was found that donors infected with type 1 showed 4 to 4.5 times greater serological reactivity by the Ortho assay than those infected with type 2 or 3. Antibody levels by the Ortho assay correlated closely to those detected by the Murex VK48 assay, and similar differences between PCR-positive and negative donors and between those infected with different genotypes were found. Differences in serological reactivity between genotypes indicate that a large proportion of epitopes of the type 1a or 1b recombinant proteins used in current assays are genotype specific. Variation in sensitivity of screening assays for different genotypes is of potential concern when used in countries where non-type 1 genotypes predominate in the blood donor or patient population.
Dhaliwal
S K
SK
Department of Medical Microbiology, University of Edinburgh, United Kingdom.
Prescott
L E
LE
Dow
B C
BC
Davidson
F
F
Brown
H
H
Yap
P L
PL
Follett
E A
EA
Simmonds
P
P
D000410:Alanine Transaminase / Q000097:blood; D001782:Blood Donors; D005838:Genotype; D016174:Hepacivirus / Q000276:immunology* / Q000302:isolation & purification; D018937:Hepatitis C Antibodies / Q000097:blood / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D011933:Reagent Kits, Diagnostic; D014766:Viremia
D018937:Hepatitis C Antibodies; D011933:Reagent Kits, Diagnostic; D000410:Alanine Transaminase