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

Maria Pia Pistillo, Pier Luigi Tazzari, Carlo Gaudiano, Vito Cilla, Tomohiro Kato, Toshihiro Matsui, Kusuki Nishioka, Paolo Capanni, Roberto Conte, Giovanni Battista Ferrara

Research output: Contribution to journalArticlepeer-review


BACKGROUND: The presence of antibodies to CTLA-4, a negative regulator of T-cell activation, was investigated in multiply transfused patients with malignant 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 storage. This study evaluated whether the same phenomenon could be involved in the induction of CTLA-4 antibodies in the patients analyzed. STUDY DESIGN AND METHODS: Patient sera were tested for binding to the recombinant full-length CTLA-4 β-galactosidase fusion protein by an ELISA. Immunofluorescence stainings were performed to analyze the CTLA-4 epitopes recognized 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 β-thalassemia (40%) and with other hemolytic diseases (33%) including leukemias (42%). A higher incidence of CTLA-4 antibodies was found in patients receiving non-WBC-reduced blood (88%) than in those receiving WBC-reduced blood (26%). Immunofluorescence staining showed that WBCs undergoing apoptosis in the RBC unit expressed CTLA4 epitopes. CONCLUSIONS: The apoptotic WBCs present in the RBC units, after cold storage, express CTLA-4 epitopes. These epitopes can be released and induce formation of CTLA-4 antibodies with profound implications in the development of autoimmune disorders and in facilitating tumor dissemination and metastasis.

Original languageEnglish
Pages (from-to)462-469
Number of pages8
Issue number4
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Hematology
  • Immunology


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