Passive Transfer of Hepatitis B Core Antibody by Intravenous Immune Globulin in Patients with Immune Thrombocytopenic Purpura.

Rituximab may reactivate remote hepatitis B infection. Thus, hepatitis B core antibody (HBcAb) seropositivity was an exclusion for a randomized trial of rituximab in patients with immune thrombocytopenic purpura (ITP) in Canada. During screening for this trial, we observed a high rate of HBcAb seropositivity at our centre. We investigated passive antibody transfer by intravenous immune globulin (IVIg) as a potential explanation.

We performed a case-control study of consecutive ITP patients screened for eligibility for a randomized trial of rituximab. We compared the frequency of prior IVIg use and the IVIg product administered to patients who tested positive (n=11) and negative (n=13) for HBcAb. Total (IgG and IgM) HBcAb was tested using a microparticle enzyme immunoassay (MEIA) that measures the rate of inhibition compared with an internal cut-off value (AxSYM®, Abbott Laboratories, IL, USA). We calculated the odds ratio (OR) and 95% confidence interval (CI) for IVIg exposure. We also tested different lots of 2 IVIg products directly for HBcAb in the MEIA.

Of 24 consecutive patients with ITP screened, 11 (45.8%) were positive for HBcAb and thus were excluded from the randomized trial. The observed rate of HBcAb seropositivity in this cohort was 35 times higher than the expected seroprevalence in Canada of 1.3% (O'Brien Transfusion 2009). Of 11 HBcAb-positive patients, 10 (90.9%) had received prior IVIg [OR, 16 (95% CI, 1.54, 166.05)]. Of the 10 patients who received IVIg, 8 (80.0%) received Gamunex (10% human immune globulin, Talecris Biotherapeutics, Clayton, NC). HBcAb was repeated in 8 seropositive patients, of whom 4 were negative on repeat testing 7 to 104 weeks after the last dose of IVIg. Of the 13 HBcAb-negative patients, 5 (38.5%) had received prior IVIg; none were Gamunex. Seroconversion was documented in one patient serially tested after receiving Gamunex; MEIA rates decreased (became positive) rapidly, then gradually increased to normal after 7 weeks. Samples from 4 lots of Gamunex were reactive in the MEIA; whereas 3 lots of IGIVnex (Talecris Biotherapeutics) were non-reactive.

False positive HBcAb results may occur due to the passive transfer of HBcAb from Gamunex, an IVIg product manufactured from donors who are not screened for HBcAb. HBcAb should be interpreted cautiously in any patient who received IVIg. We recommend HBcAb testing before IVIg administration so that treatments such as rituximab are not withheld unnecessarily.

Arnold:Hoffman-LaRoche: Research Funding; Amgen: Consultancy, Honoraria. Meyer:The NCIC CTG is a clinical trials cooperative group. It receives its base grant support from the Canadian Cancer Society Research Institute. Many of its clinical trials include research support from industry. : Research Funding.