Prolonged neutropenia resulting from antibodies to neutrophil‐specific antigen NB1 following marrow transplantation

Abstract

Marrow graft failure is a significant cause of morbidity following bone marrow transplantation. A case is reported of marrow graft failure due to neutrophil antibodies. A 13-year-old girl with a large granular lymphocytosis and chronic neutropenia was treated with granulocyte transfusions prior to undergoing a transplant with bone marrow from a partially matched, unrelated donor. Following the transplant, a bone marrow biopsy showed engraftment of donor myeloid cells, but the recipient remained neutropenic. Testing of the serum for neutrophil antibodies found that the recipient's serum had a high-titer neutrophil antibody. Immunoprecipitation studies using the marrow recipient's serum and 125I surface-labeled neutrophils showed that the antibody reacted to the neutrophil-specific antigen NB1. Phenotyping of neutrophils from the marrow donor found that they expressed NB1 antigen, and, in a crossmatch assay, the recipient's serum reacted with donor neutrophils. Despite treatment with granulocyte-macrophage--colony-stimulating factor, the marrow transplant recipient remained neutropenic and died of polymicrobial sepsis and aspergillosis 38 days after the transplant. The presence of high-titer antibodies to neutrophil-specific antigen NB1 in this patient following transplant likely prevented the recovery of her peripheral blood neutrophils and contributed to her death.

Molecular basis of NB1 (HNA-2a, CD177) deficiency

“…NB1 alloimmunization is clinically important because NB1 alloantibodies can cause immune neutropenia and transfusion-related acute lung injury. 1,[14][15][16][17][18][19] …”

Antileukemic immunity associated with antineutrophil antibody production after allogeneic hematopoietic SCT for myeloid/NK-cell precursor acute leukemia

“…Considering the kinetics of plasma cell chimerism after HSCT, 7 AIN by the alloimmune mechanism can be possible in the early stage after HSCT, and a case with graft failure caused by anti-HNA2a antibodies has actually been reported. 8 On the other hand, AIN by the autoimmune mechanism could occur with a late onset in relation to chronic GVHD, as supported by reports on the occurrence and association of autoantibodies in chronic GVHD. 9,10 The involvement of T-cell-mediated immunoderangement has been suggested as the etiology of AIN in some cases.…”

Granulocyte Antibody-Mediated Neutropenias and Transfusion Reactions

“…Recent data suggest that many cases of febrile transfusion reaction to platelet concentrates may not be immunemediated but caused by cytokines produced by contaminating leukocytes during storage [29]. Immune neutropenia following bone marrow transplantation due to the presence of granulocyte-specific alloantibodies such as anti-NA1 and anti-NB1 in the patient's blood has been reported [30,31]. However, most cases have been attributed to the formation of autoantibodies of the donor versus donor type [32].…”