title: Fewer acute rejection episodes and improved outcome in kidney-transplanted patients with selection criteria based on crossmatching.
abstract: Cross-matches performed on sera from presensitized patients have so far failed to differentiate clinically "relevant" from clinically "irrelevant" antibodies due to insufficient specificity characterization. In order to find a basis for such a possibility, 72 consecutive kidney transplanted patients were selected and studied retrospectively. Our policy has been to accept weakly positive (less than 50%) cytotoxicity on donor B splenic lymphocytes in the crossmatch test. Forty-six patients who had early acute rejections and 26 who had no acute rejections were selected for the study. Antibodies in current sera were characterized according to their target cell reactivity, immunoglobulin class, and HLA/non-HLA specificities. Crossmatches were performed using both the cytotoxicity and the flow cytometric method. We found that the factor that differentiates clinically "relevant" from clinically "irrelevant" antibodies is the HLA specificity of the lymphocyte-reactive antibodies. A high proportion of patients with posttransplant complications such as acute rejections had antibodies with specificities for HLA (particularly class I) antigens, while patients without rejections had either no detectable antibodies or antibodies reactive with non-HLA antigens only. In the present study, after elimination of false-positive reactions by ultracentrifugation of current sera, we found that flow cytometric crossmatches may not necessarily be more specific than the ordinary cytotoxicity crossmatch, since a positive flow cytometric crossmatch is often, but not always, associated with a weakly positive B cell cytotoxic crossmatch (10-25% reactivity). Antibodies causing a positive flow cytometric crossmatch could constitute low-titerd complement-fixing antibodies, non-complement-fixing antibodies, or both. Thus our study shows that it is possible to identify, prior to transplantation, patients with a risk of early posttransplant immunological complications such as acute rejection and to differentiate these from those who are more likely to have an uncomplicated posttransplant clinical course. A more careful patient selection based on adequate crossmatch testing, including specificity determination, might reduce the frequency of acute rejections and improve the outcome of transplantation.
authors.affiliation: Department of Clinical Immunology, Karolinska Institute, Huddinge Hospital, Sweden.
authors.forename: S S
authors.initials: SS
authors.lastname: Karuppan
authors.forename: A
authors.initials: A
authors.lastname: Lindholm
authors.forename: E
authors.initials: E
authors.lastname: Möller
mesh_terms: D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D005434:Flow Cytometry; D006084:Graft Rejection; D006085:Graft Survival; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*