Patients with neoplastic and nonneoplastic hematologic diseases acquire CTLA-4 antibodies after blood transfusion

BACKGROUND: The presence of antibodies to CTLA-4, a negative regulator of T -cell activation, was investigated in multiply transfused patients with mal ignant and nonmalignant hematologic diseases. A previous study showed that, in multiply transfused patients, an immune response against nuclear matrix proteins can be induced by WBCs undergoing apoptosis during RBC unit stora ge. This study evaluated whether the same phenomenon could be involved in t he induction of CTLA-4 antibodies in the patients analyzed. STUDY DESIGN AND METHODS: Patient sera were tested for binding to the recom binant full-length CTLA-4 P-galactosidase fusion protein by an ELISA. Immun ofluorescence stainings were performed to analyze the CTLA-4 epitopes recog nized by the antibodies and to detect such epitopes in the apoptotic cells present in the RBC units. RESULTS: CTLA-4 antibodies were found in multiply transfused patients with P-thalassemia (40%) and with other hemolytic diseases (33%) including leuke mias (42%). A higher incidence of CTLA-4 antibodies was found in patients r eceiving non-WBC-reduced blood (88%) than in those receiving WBC-reduced bl ood (26%). Immunofluorescence staining showed that WBCs undergoing apoptosi s in the RBC unit expressed CTLA-4 epitopes. CONCLUSIONS: The apoptotic WBCs present in the RBC units, after cold storag e, express CTLA-4 epitopes. These epitopes can be released and induce forma tion of CTLA-4 antibodies with profound implications in the development of autoimmune disorders and in facilitating tumor dissemination and metastasis .