Journal of Medical Virology 40184-187 (1993) Variability of IgM Response in Hepatitis C Virus Infection H.L. Zaaijer, L.T. Mimms, H.T.M. Cuypers, H.W. Reesink, C.L. van der Poel, S. Taskar, and P.N. Lelie zyxwvutsrq Central Laboratory zyxwvutsrq of the Netherlands Red Cross Blood Transfusion Seruice, Amsterdam, The Netherlands (H.L.Z., H.T.M.C., P.N.L.); Abbott Laboratories, North Chicago, IL (L.T.M., S.T.); Red Cross Blood Bank of Amsterdam, The Netherlands (H.W.R., C.L. ud P.) zyxwvutsr The IgM and IgG antibody response to various hepatitis C virus (HCV) antigens was studied in 8 patients who acquired posttransfusion HCV in- fection. IgM anti-HCV was detectable in only 4 of these patients, coincident with (1 patient) or later than (3 patients) the IgG anti-HCV response. Seven patients had initially decreasing IgG anti- HCV titres, indicating passive transfer of antibod- ies from donor to recipient. All 8 patients showed active IgG seroconversion, zyxwvuts as demonstrated by increasing IgG anti-HCV titres, on average, 75 days after infection. Five years after infection, all patients were still reactive for IgG anti-HCV anti- bodies and 7 were positive for HCV RNA by the polymerase chain reaction (PCR). Two of these PCR positive patients were also reactive for IgM anti-HCV. It is concluded that the serology of HCV infection does not follow the classical pat- tern of IgM response preceding detection of IgG. The IgM response may be absent, late, or persis- tent after HCV infection. The serological diagno- sis of recent HCV infection should be based on the polymerase chain reaction or rising IgG titres in at least 2 sequential patient blood samples. 1993 Wiley-Liss, zyxwvutsrqponm Inc. KEY WORDS: HCV, PCR, IgG seroconversion INTRODUCTION Non-A, non-B hepatitis has been a major risk in re- cipients of transfused blood. Choo et al. [19891 isolated genetic material of a causative agent of this disease, which has been named hepatitis zyxwvutsrq C virus (HCV). Diagno- sis of HCV infection is usually based on detection of anti-HCV antibodies. To evaluate the usefulness of IgG and IgM antibody assays for the diagnosis of early HCV infection, we studied the IgM and IgG antibody re- sponse in acute posttransfusion HCV infection. zyxwvu 0 1993 WILEY-LISS, INC. METHODS AND MATERIALS Samples In the 1980s several Dutch patients undergoing open heart surgery acquired HCV infection. Serial speci- mens from 8 of these patients were drawn at close inter- vals (mean interval 17 days) over a period of 6 months or longer. The samples were stored frozen at -30°C. Approximately 5 years after infection, another blood sample was drawn from each patient and freshly frozen at -70°C. Assays IgM and IgG antibodies to HCV were measured in all samples using a semiautomated dot blot immunoassay (Matrix, Abbott Laboratories). This assay detects anti- bodies bound to recombinant HCV antigens (~100, core, and c33) spotted onto nitrocellulose. Alanine amino transferase (ALT) levels were also determined in all specimens. HCV RNA was detected using polymerase chain reaction (PCR) on the 5’ untranslated region of the HCV genome in the samples taken 5 years after infection. RESULTS All 8 patients were seronegative for anti-HCV prior to transfusion. In the first posttransfusion blood sam- ple, 7 patients had detectable IgG anti-HCV titres which declined in the later blood sample, indicating passive transfer of antibodies from the donor to the recipient. Subsequently rising IgG anti-HCV titres in- dicated seroconversion in all patients 75 days, on aver- age, after transfusion (see Figure 1). Five patients had Accepted for publication October 20, 1992. Address reprint requests to H.L. Zaaijer, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service (or “CLB”), Viral Serology Department, Plesmanlaan 125, 1066 CX Amster- dam, The Netherlands.