Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new human antigen is reported which is present only on blood neutrophils. A neutrophil-specific antigen, designated NA1, has previously been identified in two unrelated families, and was shown to be involved in fetomaternal incompatibility and the development of isoimmune neonatal neutropenia in five newborns. In the present paper, a second antigen, designated NB1, is identified in four families with seven affected children. Antibodies that react with this second antigen are shown to produce selective agglutination of neutrophils but not other blood cells. They are neither absorbed by cells prepared from solid tissues nor by non-neutrophilic blood cells. By family and population studies, NB is shown to be distinct from NA, representing an independent genetic locus. 68% of the New York population are homozygous for NB1, 29% heterozygous, and 3% negative. The NB locus is shown to be independent from those of HL-A and other known leukocyte antigens. No evidence for linkage between NA, NB, and red cell antigens was obtained.
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PMID:NB1, a new neutrophil-specific antigen involved in the pathogenesis of neonatal neutropenia. 555 8

Neutrophils isolated from cord blood of healthy newborns (33 blacks and 21 whites) were investigated by EDTA-microagglutination for their expression of neutrophil specific antigens that have been associated with isoimmune neonatal or autoimmune neutropenia. Equal volumes of various neutrophil antisera (2 microliter) and cord neutrophils (3-5 X 10(6)/ml) were mixed in tissue typing microplates under oil and were incubated at room temperature for 6-8 hr, following which the degree of agglutination was noted. Our data revealed that all the currently recognized neutrophil antigens are readily demonstrable by antineutrophil antibodies in cord blood, (NA1, 52-54%; NA2, 81-85%; NB1, 95-96%; NC1, 90%; 9A, 29-30%) suggesting that neutrophil antigens are fully expressed at birth.
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PMID:Incidence of neutrophil antigens on human cord neutrophils. 608 28

Fourteen infants with autoimmune neutropenia reported in the literature have been reviewed. Autoantibodies directed against their own neutrophils were demonstrated in the sera of these infants by agglutination, complement-dependent cytotoxicity, and immunofluorescence techniques. These antibodies were highly specific and were directed against antigens present on neutrophils. Among the currently known neutrophil antigens (NA1, NA2, NB1, NC1, NE1, ND1, 9A), antibodies reacting with either NA1 or NA2 have been identified frequently in the sera of infants with autoimmune neutropenia. Good correlation was demonstrated between the presence or absence of autoantibodies and the episodes of neutropenia in many cases. Antibodies from the patients also reacted with neutrophils from their parents and from normal unrelated volunteers when they shared the neutrophil-specific antigen against which the antibody was directed. Antibodies demonstrable by complement-dependent cytotoxicity appeared to detect different antigens which may also cause autoimmune neutropenia. Infants with this disorder were healthy at birth and for a few months afterwards, then became chronically ill with such symptoms as intermittent fever, diarrhea, and infections. Their hemoglobin levels, lymphocyte and platelet counts, and other immunological studies were normal except for severe to moderate neutropenia.
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PMID:Autoimmune neutropenia in early infancy: a review. 675 24

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.
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PMID:Prolonged neutropenia resulting from antibodies to neutrophil-specific antigen NB1 following marrow transplantation. 843 Apr 56

The following substances were tested for their influence on granulocyte function: 8 sera that contained human granulocyte-specific alloantibodies against the antigens NA1, NA2 and NB1, two HLA antisera, and the monoclonal antibodies W6/32 and CLB-FcR-gran 1. The effects examined included spontaneous and directed migration, immune phagocytosis inhibition and the generation of oxygen radicals. Using the under-agarose technique, spontaneous migration of sensitized granulocytes was normal. For all antibodies tested, the chemotactic index for N-fMLP, LTB4 and opsonized zymosan was greater than 1. Granulocyte immune phagocytosis of sensitized sheep red blood cells was strongly inhibited by all alloantisera and monoclonal antibodies. The generation of oxygen radicals after triggering the respiratory burst with sensitized sheep red blood cells was also strongly inhibited in the chemiluminescence assay. Immune phagocytosis and chemiluminescent response of granulocytes lacking the corresponding antigen of the tested alloantibodies were not affected. Since sensitization of neutrophils with F(ab')2 fragments of the monoclonal antibodies W6/32 and CLB-FcR-gran 1 showed lower inhibition of generation of oxygen radicals after triggering, Fc-dependent interaction with the target cells seems to be necessary for inhibition. Our results suggest that binding of NA1-, NA2- or NB1-specific alloantibodies to granulocytes not only causes neutropenia, but also impairs granulocyte function.
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PMID:Influence of granulocyte antibodies on granulocyte function. 851 50

Several advances have been made in understanding the polymorphisms of the neutrophil Fc-gamma-receptor IIIb (Fc gamma RIIIb). In one recent study, 21 individuals whose neutrophils lack Fc gamma RIIIb were found to be missing the entire Fc gamma RIIIB and Fc gamma RIIC genes. Another polymorphism of Fc gamma RIIIb, SH, has been characterized. New methods to determine the genotype of Fc gamma RIIIB for NA1, NA2, and SH using leukocyte genomic DNA have been described. A new monoclonal antibody to neutrophil-specific antigen NB1 was produced. Advances have been made in understanding alloimmunization in granulocyte transfusion recipients and the treatment of autoimmune neutropenia with granulocyte colony-stimulating factor (G-CSF). Granulocyte transfusion recipients were found to be alloimmunized both to neutrophil-specific and HLA antigens, suggesting that the transfusion of these patients with granulocytes matched only for HLA antigens will not be effective. A case report suggests that the beneficial effects of G-CSF on patients with autoimmune neutropenia is due in part to G-CSF's action of increasing plasma levels of soluble Fc gamma RIIIb.
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PMID:Neutrophil antibodies. 935 5

Alloimmune neonatal neutropenia (ANN) is an uncommon but potentially life-threatening disorder of the neonate and young infant. Hematologically, the mother's peripheral neutrophil count is normal. However, the passive transfer of maternal immunoglobulin G neutrophil-specific antibodies and the subsequent sensitization of fetal neutrophils can result in severe neutropenia in the neonate. Generally, ANN is a self-limiting condition, but with severe bacterial infection, mortality can be high. We present the clinical features of monozygous twins delivered at 33 weeks' postconception with this condition. This case report is unique in that it occurred in twins born prematurely and was attributable to antibodies against 2 neutrophil-specific antigens, NA1 and NB1. A brief review of the diagnosis, management, and treatment of ANN is presented.
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PMID:Neonatal alloimmune neutropenia in premature monozygous twins. 1092 Jan 62

A case of immune neutropenia following unrelated stem cell transplantation for chronic myeloid leukaemia is described. The neutropenia developed following herpes zoster viral infection and was associated with antibodies to the human neutrophil antigen (HNA)-2a (formerly known as NB1). The neutropenia was prolonged, profound and unresponsive to granulocyte colony-stimulating factor (GCSF). The neutrophil count recovered after GCSF was discontinued. HNA-2a has been reported to be upregulated following GCSF administration. In the present case, it appears that the immune neutropenia may have been perpetuated by GCSF administration.
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PMID:Immune neutropenia associated with anti-human neutrophil antigen-2a (NB1) antibodies following unrelated donor stem cell transplantation for chronic myeloid leukaemia: perpetuation by granulocyte colony-stimulating factor. 1138 Apr 20

Antibodies directed against antigens on the granulocyte (neutrophil) membrane can cause a variety of disorders including neonatal immune neutropenia, immune neutropenia after bone marrow transplantation, autoimmune neutropenia, and drug-induced immune neutropenia. Since granulocyte alloantibodies can lead to severe pulmonary transfusion reactions (TRALI), febrile transfusion reactions and refractoriness to granulocyte transfusions, they also play an important part in blood transfusion. The implicated human neutrophil alloantigens (HNA) have been renamed in the recently introduced HNA nomenclature which is based on the antigen's glycoprotein location. The Fc gamma Receptor IIIb (CD16, HNA-1) and the NB1 glycoprotein (CD177, HNA-2) represent the major immunogenic molecules of the neutrophil membrane. They bear the clinically most important antigens HNA-1a,-1b,-1c (NA1, NA2, SH) and HNA-2a (NB1), respectively. For the detection of granulocyte antibodies, a combination of immunofluorescence and agglutination tests together with a panel of freshly isolated, typed test neutrophils has been shown to represent the best means of detection. The introduction of the glycoprotein-specific assay "MAIGA" has improved alloantibody identification considerably. To facilitate and improve neutrophil typing, PCR-SSP techniques have been established for HNA-1a,-1b, and -1c genotyping.
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PMID:Granulocyte immunology. 1173 15

Antibodies to neutrophil antigens can cause neonatal alloimmune neutropenia, autoimmune neutropenia, febrile transfusion reactions, and transfusion-related acute lung injury. Several neutrophil antigen systems have been described serologically, but only the human neutrophil antigen-1 (HNA-1) or NA and HNA-2 or NB systems have been well characterized biochemically and molecularly. HNA-1 antigens are located on FcgammaRIIIb, CD16. HNA-2 antigens are located on 58- to 64-Kd glycoprotein, CD177, and are encoded by a gene on chromosome 19 that belongs to the Ly-6 family. The function of the CD177 is not known, but the CD177 gene is highly homologous to a gene overexpressed in neutrophils from patients with polycythemia rubra vera called PRV-1. New polymorphisms in these antigen systems are still being described, but the complete understanding of these neutrophil antigen systems has been slow because of the complexity of these genes.
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PMID:Neutrophil alloantigens. 1178 31


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