Low-affinity, cold-reactive antibodies easily removed by washing were not detected by the antiglobulin technique but killed T lymphocytes when washing was omitted, incubation was prolonged, and cytotoxic tests were incubated at room temperature or at 4°C. These antibodies were present in approximately 25% of sera from dialysis patients. Only a subset of such sera (22%) reacted with autologous lymphocytes. The majority (86%) appeared to detect non-HLA antigens. A small number (14%) detected class IHLA antigens. Two patients transplanted with antiglobulin-negative, T-warm-negative crossmatch results, but positive cytotoxicity after a 2hr incubation without washing, rapidly lost their grafts (<1 month) due to rejection. Their sera contained antibodies against non-HLA alloantigens expressed on lymphocytes and platelets, but not on granulocytes or erythrocytes. Two other patients with positive autoantibody tests exhibiting similar crossmatches with the current serum were transplanted recently. Both of them retain their grafts with good function at one month. In two other cases, the recipients were unreactive against the donor in current serum but displayed an antiglobulin-negative, 2-hr cytotoxicity-positive pattern in a previously drawn serum specimen. One patient continues to have stable renal function after 10 months. The other patient lost the transplant as a result of renal artery thrombus thought not to be immunologic in origin. Work is continuing to define the specificity and determine the clinical relevance of such cold-reactive antibodies.
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