Lytic DSAs as the qualification criterion for virtual crossmatch test. Benefits and challenges

Abstract

Pre-formed anti-HLA antibodies against the potential donor antigens (donor-specific antibodies, DSA) are a prevalent risk factor significantly reducing the patient’s chances of receiving a transplant. Pre-transplantation immunization assessments consist mainly of the high-sensitivity anti-HLA fluorescence flow cytometry assays (Luminex). The assays facilitate the determination of the specificity of anti-HLA antibodies within the entire range of the IgG class, including the subclasses of non-lytic antibodies, such as IgG2 and IgG4, which are significantly less harmful to the transplant as compared to lytic antibodies. When the results of anti-HLA IgG assays are taken into account as the only qualification criterion for virtual crossmatching without their lytic potential being determined, the recipient’s chances for transplantation are significantly reduced. In view of the problem of the increasing number of immunized patients, a modification of the virtual crossmatching protocol is proposed so that only recipients with anti-HLA antibodies identified as complement-binding [C1q(+)] DSAs are excluded from the further qualification process. The presence of C1q(−) DSAs would be an indication of increased risk of humoral rejection rather than contraindication for transplantation. The results of transplantations followed by strict monitoring of antibody levels in these patients are promising albeit burdened by increased risk of humoral rejection. This article presents the benefits and challenges related to the introduction of the new algorithm focusing particularly on the interpretation of the C1q status of donor-specific antibodies.