Alloimmunization after granulocyte transfusions

Although granulocyte transfusions are recommended for neutropenic patients with bacterial infections that are unresponsive to antibiotic therapy, the presence of white cell (WBC) antibodies in the recipient can render these transfusions ineffective.

A 25-year-old man with chronic granulomatous disease experienced a pulmonary transfusion reaction while receiving granulocyte transfusions, and he was found to be immunized to neutrophil antigen NA2. A retrospective study of alloimmunization to HLA and neutrophil antigens in 18 patients with chronic granulomatous disease who had also received repeated granulocyte transfusions was then performed. Sera were tested in lymphocytotoxicity, granulocyte agglutination, granulocyte immunofluorescence, monoclonal antibody immonobilization of granulocyte antigen, and immunoprecipitation assays.

After the granulocyte transfusions, sera from 14 of the 18 patients contained WBC antibodies. Seven sera samples reacted in the lymphocytotoxicity, granulocyte immunofluorescence, and granulocyte agglutination assays; seven reacted in the lymphocytotoxicity and granulocyte immunofluorescence assays but not the granulocyte agglutination assay, and four did not react. When the monoclonal antibody immobilization of granulocyte antigen assay was used, three sera samples reacted with Fc gamma receptor III, three with the 58- to 64-kDa protein carrying the neutrophil antigen NB1, one with CD11a, and one with CD18. Antibodies from three patients immunoprecipitated a neutrophil protein of 60 kDa. Overall, antibodies to neutrophil antigens other than HLA could be detected in sera from eight patients. Transfusion reactions occurred in 11 of the 14 individuals with WBC antibodies and in none of the 4 without antibodies. Seven pulmonary reactions occurred in patients with WBC antibodies. The patients with WBC antibodies were given significantly more granulocyte concentrates (78 +/- 65 vs. 29 +/- 15 units, p < 0.05).

Recipients of granulocyte transfusions often become alloimmunized. Screening for WBC antibodies periodically during transfusions, after adverse reactions, or before subsequent transfusions is indicated. If WBC antibodies are present, no further granulocyte transfusions should be given unless the granulocytes are collected from HLA- and/or neutrophil antigen-compatible donors.