Granulocyte immunology: is there a need to know?

A lthough the technical development of granulocyte immunology lags behind that of platelet and lymphocyte immunology, work in this field has I progressed substantially in the past decade and further investigation is warranted. A significant advancement of the field is reported in this issue ofTRANSFUSION, the results of the most recent granulocyte antigen workshop. ' This workshop, as with those that have been held for HLA, platelet, and red cell antigens, requires considerable effort on the part of the organizers and the willingness of the expert laboratories to share valuable reagents and to collaborate in their analysis. These workshops, however, have contributed substantially to increased scientific knowledge of alloantibodies and alloantigens. The technology used in the typing of HLA and plateletspecific antigens and in testing for antibodies to these antigens has changed dramatically. Almost all clinically important HLA and platelet-specific antigens can be typed by molecular techniques. Solid-phase tests are available to rapidly screen multiple samples for antibodies to HLA and platelet antigens. The HLA antigen and antibody tests are important for bone marrow and organ transplantation and the platelet assays are critical in the diagnosis of neonatal alloimmune thrombocytopenia and posttransfusion purpura. In contrast, progress in the typing of granulocyte antigens and in testing for antibodies to granulocyte antigens has been much slower and the need to test for these antibodies and antigens has been less apparent to clinicians. The detection of antibodies to granulocyte-specific antigens and the determination of granulocyte antigen phenotypes and genotypes are clinically important. However, diseases that benefit from granulocyte antibody and antigen testing, such as neonatal alloimmune neutropenia and autoimmune neutropenia, are rare. Identification of granulocyte-specific alloantibodies in neutropenic neonates and their mothers distinguishes alloimmune neutropenia from congenital neutropenia and neutropenia due to sepsis. The simple detection of a granulocyte antibody in a child can quickly differentiate autoimmune neutropenia from other hematologic diseases without a bone marrow biopsy. The clinical presentation of autoimmune neutropenia is more complicated in adults than in children, and the identification of a granulocyte-specific antibody is an important diagnostic tool. The diagnosis of autoimmune neutropenia is critical in both children and adults, because they can be treated effectivelywith granulocyte-colony-stimulating factor (GCSF). 2 Granulocyte alloantibodies have been reported to cause a delayed recovery of myeloid cells following marrow transplantation and the occurrence of drug-dependent neutro~ e n i a . ~ ~ They are also implicated in febrile transfusion reactions and transfusion-related acute lung injury (TRALI). TRALI, a serious complication associated with transfusions, is estimated to occur in 1 in 4500 transfusions.6 Whereas febrile reactions are due to antibodies produced by the transfusion recipient, TRALI is due to antibodies passively acquired from the transfused blood component. Patients receiving granulocyte transfusions can become alloimmunized to both HLA and granulocyte antigen^. ^ The presence of granulocyte alloantibodies in granulocyte transfusion recipients often decreases the survival and targeted migration of donor granulocyte^. ^^^ They can also induce pulmonary transfusion reactions in the granulocyte transfusion re~ipient . ~ When considering the clinical importance of granulocyte antibodies, one might think that the development of rapid and reliable diagnostic techniques would have progressed more quickly. Progress in the field of granulocyte immunology has been hampered by the technical difficulties involved in working with granulocytes. Traditionally, the screening of sera for granulocyte antibodies and the phenotyping of granulocytes have been performed with fresh cells in agglutination, cytotoxic, immunofluorescence, or flow cytometric assays. Granulocytes for these assays must be isolated from blood by a red cell sedimentation process followed by a density gradient white cell-separation technique that requires several hours. The short ex vivo shelf life of granulocytes, the limited ability of granulocytes to be maintained at 4"C, and the inability to cryopreserve granulocytes necessitate that fresh granulocytes must be prepared whenever testing is performed. ~ ~~ _____