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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Alloimmunization to the neutrophil antigen NB1 (HNA-2a, CD177) can result in immune neutropenia and transfusion-related acute lung injury. Recently, we were able to elucidate the primary structure of NB1. To shed light also on the molecular basis of the NB1-negative phenotype, we studied the neutrophils of 2 women with NB1-specific alloantibodies for intracellular and extracellular NB1 expression, NB1-specific mRNA production, and the presence of the NB1 gene. No antibody binding to neutrophils was observed by immunofluorescence and immunoblot using a variety of human and monoclonal NB1-specific antibodies. By reverse transcription-polymerase chain reaction with NB1-specific primers we could not detect NB1 cDNAs without accessory sequences, which were found to be introns. The NB1 gene was present in the genome of both patients. Our data indicate that the NB1-negative phenotype is the result of different off-frame insertions on RNA level, resulting in NB1 deficiency on neutrophils.
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PMID:Molecular basis of NB1 (HNA-2a, CD177) deficiency. 1201 Aug 33

Granulocyte (neutrophil) antibodies can cause autoimmune neutropenia, drug-induced neutropenia, immune neutropenia after bone marrow transplantation, neonatal immune neutropenia, refractoriness to granulocyte transfusions as well as febrile and pulmonary transfusion reactions. In the last decade, considerable progress has been made in the characterization of the implicated antigens. In 1998, the Granulocyte Antigen Working Party of the ISBT introduced a new nomenclature for human neutrophil alloantigens (HNA), which is based on the antigens' glycoprotein location. In the HNA nomenclature the immunogenic (glyco-) proteins are indicated by arabic numbers followed by a letter of the alphabet which identify the (glyco-) proteins' polymorphisms, i.e. the specific antigens. Currently, seven HNA antigens are assigned to five systems. The HNA-1a, HNA-lb and HNA-1c antigens, the former NA1, NA2, and SH antigens, have been identified as polymorphic forms of the neutrophil Fc gamma receptor IIIb (CD16b) encoded by three alleles. Recently, we could elucidate the primary structure of the HNA-2a antigen, the former NB1. We could identify the HNA-2a-bearing glycoprotein as a novel member of the Ly-6/uPAR superfamily which has been clustered meanwhile as CD177. The HNA-3a antigen, the former 5b, is located on a 70-95 kDa glycoprotein. However, its molecular basis is still unknown. Finally, the HNA-4a and HNA-5a antigens, the former MART and OND, were found to be caused by single nucleotide mutations in the alphaM (CD11b) and alphaL (CD11a) subunits of the leucocyte adhesion molecules (beta2 integrins). The glycoproteins CD11b, CD16b, and CD177 have been found to be also frequent targets of autoantibodies - approximately 30% of neutrophil autoantibodies are directed against CD16b. Characterization of granulocyte antigens have expanded our diagnostic tools by the introduction of genotyping techniques and immunoassays for antibody identification. In addition, it allowed new insights in the pathophysiology of immune neutropenias and transfusion reactions. Ongoing studies will further improve the prevention and management of granulocyte antibody-mediated diseases.
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PMID:Molecular nature of antigens implicated in immune neutropenias. 1243 Aug 90

Human neutrophil antigen 2 (HNA-2) deficiency is a common phenotype as 3-5% humans do not express HNA-2. HNA-2 is coded by CD177 gene that associates with human myeloproliferative disorders. HNA-2 deficient individuals are prone to produce HNA-2 alloantibodies that cause a number of disorders including transfusion-related acute lung injury and immune neutropenia. In addition, the percentages of HNA-2 positive neutrophils vary significantly among individuals and HNA-2 expression variations play a role in human diseases such as myelodysplastic syndrome, chronic myelogenous leukemia, and gastric cancer. The underlying genetic mechanism of HNA-2 deficiency and expression variations has remained a mystery. In this study, we identified a novel CD177 nonsense single nucleotide polymorphism (SNP 829A>T) that creates a stop codon within the CD177 coding region. We found that all 829TT homozygous individuals were HNA-2 deficient. In addition, the SNP 829A>T genotypes were significantly associated with the percentage of HNA-2 positive neutrophils. Transfection experiments confirmed that HNA-2 expression was absent on cells expressing the CD177 SNP 829T allele. Our data clearly demonstrate that the CD177 SNP 829A>T is the primary genetic determinant for HNA-2 deficiency and expression variations. The mechanistic delineation of HNA-2 genetics will enable the development of genetic tests for diagnosis and prognosis of HNA-2-related human diseases.
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PMID:Genetic mechanism of human neutrophil antigen 2 deficiency and expression variations. 2611 43

Most humans harbor both CD177neg and CD177pos neutrophils but 1-10% of people are CD177null, placing them at risk for formation of anti-neutrophil antibodies that can cause transfusion-related acute lung injury and neonatal alloimmune neutropenia. By deep sequencing the CD177 locus, we catalogued CD177 single nucleotide variants and identified a novel stop codon in CD177null individuals arising from a single base substitution in exon 7. This is not a mutation in CD177 itself, rather the CD177null phenotype arises when exon 7 of CD177 is supplied entirely by the CD177 pseudogene (CD177P1), which appears to have resulted from allelic gene conversion. In CD177 expressing individuals the CD177 locus contains both CD177P1 and CD177 sequences. The proportion of CD177hi neutrophils in the blood is a heritable trait. Abundance of CD177hi neutrophils correlates with homozygosity for CD177 reference allele, while heterozygosity for ectopic CD177P1 gene conversion correlates with increased CD177neg neutrophils, in which both CD177P1 partially incorporated allele and paired intact CD177 allele are transcribed. Human neutrophil heterogeneity for CD177 expression arises by ectopic allelic conversion. Resolution of the genetic basis of CD177null phenotype identifies a method for screening for individuals at risk of CD177 isoimmunisation.
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PMID:Heterogeneity of Human Neutrophil CD177 Expression Results from CD177P1 Pseudogene Conversion. 2722 54

We describe a patient who presented with prolonged neutropenia due to anti-human neutrophil antigen (HNA)-2 (CD177) antibody after allogeneic bone marrow transplantation. A granulocyte immunofluorescence test showed bimodal expression of antineutrophil antibody that resulted from specific binding of anti-HNA-2 to CD177+ neutrophils from healthy donors. The patient did not respond to granulocyte colony stimulating factor, which is able to upregulate CD177 expression on neutrophils. The low percentage of CD177+ cells in the few remaining neutrophils supports the possibility of elimination of CD177-upregulated neutrophils. These findings might explain an inferior response to neutrophil growth factors in neutropenia secondary to anti-HNA-2 antibody.
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PMID:Prolonged neutropenia due to antihuman neutrophil antigen 2 (CD177) antibody after bone marrow transplantation. 2790 83

Granulocytes are an essential part of both the innate and adaptive immune systems. Human neutrophil antigens (HNAs) are a family of epitopes that are located on glycoproteins that are mostly expressed on human granulocytes. Antibodies that recognize these epitopes have been associated with neutropenia, transfusion complications, haematopoietic stem cell transplant nonengraftment and renal transplant rejection. Currently, there are fourteen recognized HNA alleles across five antigen systems (HNA-1 through HNA-5), the molecular basis of which are located on the genes FCGR3B, CD177, SLC44A2, ITGAM and ITGAL, respectively. Elucidation of the associated genes has permitted the development of testing strategies for HNA typing and aided understanding of the associated epitopes. This review will outline the associated clinical conditions that require HNA investigation and how these are performed in specialized laboratories. Investigations provided are both reactive for patients with a variety of existing or suspected neutropenias and proactive in the testing of blood component donors in order to reduce the potential risk to patients who require transfusion.
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PMID:Human neutrophil antigens: Nature, clinical significance and detection. 3297 Mar 72