Detection of antibodies to hepatitis C virus: false-negative results in an automated chemiluminescent microparticle immunoassay (ARCHITECT Anti-HCV) compared to a microparticle enzyme immunoassay (AxSYM HCV Version 3.0).

Background: Following an accidental observation of reduced sensitivity for detection of antibodies to hepatitis C virus (HCV) with a novel commercially available automated chemiluminescent microparticle immunoassay (CMIA, ARCHITECT Anti-HCV) compared to a well-established microparticle enzyme immunoassay (MEIA, AxSYM HCV Version 3.0), we wanted to explore whether this could be explained by a variation in marginal sensitivity, to be expected between highly sensitive assays of different formats, or represented a reduced sensitivity of the CMIA to certain antibody profiles.

Objectives: To evaluate the ability of the CMIA to detect low concentrations of anti-HCV antibodies as defined by various patterns in the recombinant immunoblot assay (RIBA) and already detected in the MEIA system.

Study Design: All patient sera tested for anti-HCV reactivity during a period of 3 years (27,978) were evaluated. A total of 90 sera had a sample/cut-off ratio (S/CO) between 1.0 and 1.5 in the MEIA test and were available for further testing. Of these, 19 had a probable/possible presence of anti-HCV antibodies based on presence of at least two bands of > or = 1+ strength in the RIBA, or because the patient was known to be anti-HCV positive. These 19 sera were tested with the CMIA. In addition, 16 sera with strong reactivity to various antigen combinations in the RIBA were serially diluted until testing negative in both microparticle test systems.

Results: Seven of the 19 sera (37%) were negative (S/CO < 1.0) in the CMIA. At least 3 (16%) of these 19 sera were very likely to be true anti-HCV positive sera (from infants with known anti-HCV positive mothers). HCV-RNA was not detected in any of the sera tested. Testing of sera after serial dilution indicates that the CMIA has a lower sensitivity to c22- and c33c-antibodies than the MEIA, possibly also to c100-3-antibodies.

Conclusion: Our findings indicate that ARCHITECT Anti-HCV is less sensitive than AxSYM HCV Version 3.0 in detecting antibodies to c22 and c33c in patients who have cleared their HCV-infection and have naturally declining levels of antibodies.