THE OCCURRENCE OF CYTOTOXIC AND NONCOMPLEMENT-FIXING ANTIBODIES IN THE CROSS-MATCH SERUM OF PATIENTS WITH EARLY ACUTE REJECTION EPISODES

In an earlier study we found a strong correlation between the presence of donor-reactive HLA-specific antibodies in the crossmatch serum and early acute rejection episodes. Our experience was also that some of these antibodies were not cytotoxic and could therefore not be detected using the microcytotoxicity assays. In the present study, 11 patients from the earlier study who had weakly positive B cell reactive cytotoxic antibodies of the IgG class were further characterized. In addition, 14 new patients were selected who experienced early acute rejections but had a completely negative donor-B cell cytotoxicity crossmatch. A group of 12 controls without immunological complications was added, as well as 5 patients with early graft losses due to nonimmunological causes. Using the flow cytometric crossmatch test we confirmed the presence of HLA-specific antibodies in all 11 patients from the earlier study. In addition, positive flow cytometric crossmatches shown to be caused by HLA antibodies were observed in 11 of the 14 patients with acute rejections and negative cytotoxic crossmatch. One of 17 control patients had antibodies that were not HLA-reactive. IgA antibodies as well as IgG subclass determinations were performed in all positive sera. A substantial proportion of patients had HLA-specific antibodies of non-complement-binding classes (IgG2, IgG4, IgA) often of higher titers than IgG1 and IgG3. The subclass distribution pattern was heterogeneous and often included several subclasses. We conclude that non-complement-fixing antibodies can also contribute to the risk for development of early acute rejections after necrokidney transplantation. Immunological mechanisms for these findings are discussed.