Significance of highly positive c22-3 "indeterminate" second-generation hepatitis C virus (HCV) recombinant immunoblot assay (RIBA) and resolution by third-generation HCV RIBA

Abstract

Second-generation recombinant immunoblot assay (RIBA) is widely used for the validation of anti-hepatitis C virus (HCV) antibody detection. The aims of this work were (i) to determine, in terms of liver disease and HCV replication, the significance of a peculiar "indeterminate" second-generation RIBA pattern characterized by the presence of high titers of antibodies directed to c22-3, a protein bearing core epitopes and (ii) to determine whether a more advanced version of the same strip assay, namely a third-generation RIBA, may solve the problem of such indeterminate patterns. Sixty patients for which c22-3 indeterminate secondgeneration RIBAs were highly positive were studied. Forty-two of them (709%) were immunocompromised. Serum transaminases were increased in 46 cases (77%), and HCV RNA was detected by PCR in 50 cases (83%). Third-generation RIBA remained highly positive c22 indeterminate for 9 patients (15%) but was positive for 51 (85%), mostly because of increased sensitivity for the detection of both anti-clOO and anti-c33c antibodies.

Genetic complexity of the hypervariable region 1 (HVR1) of hepatitis C virus (HCV): Influence on the characteristics of the infection and responses to interferon alfa therapy in patients with chronic hepatitis C

“…To assess the virological response to treatment, HCV RNA was tested in the serum of patients with a sustained biochemical response to IFN therapy at month 12, by using a highly sensitive RT ''nested'' PCR procedure [Pawlotsky et al, 1994].…”

Antibody responses to hepatitis C envelope proteins in patients with acute or chronic hepatitis C

“…These tests, which allowed the detection of antibodies against recombinant proteins from NS4 (c100-31, C (c22-31, and NS3 (c33c) regions, have exhibited higher sensitivity [Bresters et al, 1992;Katayama et al, 19921. More recently, third-generation assays were developed including parts of C, NS3, NS4, and NS5 proteins Wernelen et al, 19941. Due to the improvement in the antigenicity of the NS3 and NS4 proteins, these tests have greatly ameliorated the sensitivity and specificity of HCV antibody detection [Pawlotsky et al, 1994;Uyttendaele et al, 19941. The methods used to examine the antigen-antibody reactivity vary with the test (enzyme-linked assays, EL4 or ELISA, or recombinant immunoblot assays) as well as range" (ULNR) and negative for anti-HIV Ab, anti-HTLV Ab, HBs Ag, anti-HBc Ab, anti-HCV Ab, antimalarial Ab, and VDRL.…”

Evaluation of the persistence and characteristics of indeterminate reactivity against hepatitis C virus in blood donors

“…Indeterminate reactivity against the c22 antigen was the rarest finding, present in approximately one-fifth of the donors. The finding of a c22 band in RIBA may be highly indicative of previous HCV exposure, [12][13][14][15] and donors with this serologic profile should probably be excluded even in spite of a subsequent seroreversion to RIBA negative.…”