New hepatitis B virus mutant form in a blood donor that is undetectable in several hepatitis B surface antigen screening assays.

BACKGROUND: Envelope mutant forms of hepatitis B virus (HBV), impairing HBV antibody recognition, have been reported with mutations in single or multiple sites of the hepatitis B surface antigen (HBsAg) group-specific "a" determinant. Blood donors infected with such an HBsAg mutant form of HBV may escape detection by HBsAg screening assays and therefore may affect the safety of the blood supply. CASE REPORT: A repeat blood donor became HBsAg-reactive in an enzyme immunoassay. Confirmatory testing yielded negative results for HBsAg in a radioimmunoassay and in four enzyme immunoassays used in blood donor screening. The specificity of the HBsAg reactivity in the first enzyme immunoassay was confirmed by HBsAg neutralization with antibody to HBsAg. Additional HBV confirmatory test results were positive for antibody to hepatitis B core antigen and antibody to hepatitis B e antigen; negative for antibody to HBsAg and for hepatitis B e antigen; and positive for HBV DNA. DNA sequence analysis of the "a" determinant region of HBsAg revealed amino acid substitutions from Q (Gln) to R (Arg) at codon 129 and from M (Met) to T (Thr) at codon 133. CONCLUSION: This case illustrates the presence of HBsAg mutant forms of HBV in a West European blood donor population that were undetected by several HBsAg screening assays. Adaptation of HBsAg screening is indicated to overcome deficiencies in sensitivity in detecting HBsAg mutant forms of HBV. Screening for antibody to hepatitis B core antigen or HBV DNA may also detect blood donors infected with HBsAg mutant forms of HBV

Prevention of donor-specific T-cell unresponsiveness after buffy-coat-depleted blood transfusion.

The immunosuppressive effect of blood transfusions has been demonstrated in several clinical studies. The effect is probably mediated by HLA-class-II-bearing donor leucocytes, because results from laboratory tests show specific down-regulation of the recipient's T-Cell response after administration of blood from donors sharing one HLA haplotype with the recipient. In the present study we evaluated the immunosuppressive potential of buffy-coat-depleted red cell transfusions in patients waiting for renal transplantation, by measuring the frequency of cytotoxic precursor T cells before and after transfusion. The buffy coat was removed from whole blood by the Optipress system and resulted in > 97% depletion of lymphocytes and monocytes. A single transfusion of HLA-haplotype-matched buffy-coat-depleted red cells induced donor-specific down-regulation of T-cell responses in only two of 14 patients. Since HLA-class-II-bearing cells are also involved in the induction of anti-HLA antibodies, we evaluated retrospectively the incident of HLA alloimmunization after a single transfusion of buffy-coat-depleted red cells. No anti-HLA antibodies were found in 140 patients at risk for primary immunization. We conclude that the poor immunological responses found after a single transfusion of HLA-haplotype-matched buffy-coat-depleted red cells is due to the small number of residual HLA-class-II-bearing donor cells. This blood component should not be used for induction of immunosuppression.

Prevention of primary transfusion-associated cytomegalovirus infection in bone marrow transplant recipients by the removal of white cells from blood components with high-affinity filters.

A prospective study was carried out to determine whether use of cytomegalovirus (CMV) unscreened red blood cells and platelet concentrates, white blood cell (WBC) depleted with high-efficiency filters, would prevent transfusion-associated (TA) CMV infection in CMV seronegative bone marrow transplant recipients. Blood components were filtered in the bloodcentre under quality control and after filtration residual WBC counts were always below 5 x 10(6) cells/U. Since 1990, 23 consecutive allogeneic and 37 autologous CMV seronegative marrow transplant recipients, have been transfused with filtered blood components and followed for 6 months for evidence of CMV infection by monitoring culture and CMV serology. None of the patients showed clinical symptoms of CMV infection, and CMV cultures during episodes of fever were always negative. IgM anti-CMV antibodies were negative during the study in all patients. Low titres of IgG anti-CMV antibodies (5-12 relative ELISA units) were found in 24/60 patients during the first month after bone marrow transplantation (BMT), probably due to passive transfer of IgG administered with the platelet transfusions. 3 and 6 months after BMT, 56 and 48 patients respectively were still alive; and CMV serology was negative in all patients. The results show that TA-CMV infection is preventable by filtration of blood through high-efficiency filters in patients undergoing autologous and allogeneic BMT.