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

Neutrophil antibodies frequently cause severe conditions such as transfusion-related acute lung injury, alloimmune/autoimmune neutropenia. As it was thought that surviving neutrophils would also be damaged from antibodies binding with the neutrophil membrane, we studied the functional influence of neutrophil antibodies on natural phagocytosis and immune phagocytosis by using neutrophil-specific monoclonal antibodies (MoAbs), TAG1: HNA-la on FgammaRIIIb, TAG2: HNA-1b on FgammaRIIIa/b, TAG3: FgammaRIIIa/b and TAG4: HNA-2a. In an inhibition assay of carbon particle phagocytosis as a representation of natural phagocytosis, neutrophils binding with TAG3 or TAG4 were inhibited from carbon particle-phagocytosis by 42.5% and 53.2% (% inhibition), respectively, but in an inhibition assay using TAG3 MoAb, HNA-2a strongly positive neutrophils were more weakly inhibited than HNA-2a weak-positive neutrophils, 39.2% and 54.0% (% inhibition), respectively. These results suggested that HNA-2a salvaged the inhibition process of natural phagocytosis by anti-FcgammaRIII antibodies. These results also suggested that natural phagocytosis would be inhibited when antibodies combined with every antigen on the cell membrane. In an inhibition assay of EA-rosette formation as a representation of immune phagocytosis, FcgammaRIII-specific MoAbs, TAG1, TAG2 and TAG3 inhibited EA-rosette formation, but HNA-2a-specific MoAb, TAG4, did not markedly inhibit EA-rosette formation. It was thought that neutrophil immune-phagocytosis would be inhibited by antibodies binding with FcgammaRIII, and that HNA-2a was not related to immune phagocytosis. Further investigation of the relationship between clinical symptoms and antibody specificity or antibody quantity is needed.
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PMID:[Influence of monoclonal antibodies to human neutrophil antigens, HNA-1a/b and HNA-2a on phagocytosis]. 1815 30

Alloimmunization to granulocyte-specific antigens can occur during pregnancy. Maternal antibodies of IgG class can cross the placenta to result in alloimmune neonatal neutropenia. Antibodies to human neutrophil antigens anti-HNA-1a, HNA-1b, and HNA-2a have been most commonly reported to cause alloimmune neonatal neutropenia. Isoantibodies to Fc gamma RIIIb (CD16) if mother is a HNA-null phenotype are rarely involved in neonatal neutropenia. We report on a case of severe neutropenia (440 neutrophils/muL) due to anti-Fc gamma RIIIb (CD16) isoimmunization. On day 14 severe omphalitis developed, which was treated for 7 days by an antibiotic (ceftriaxone in a dose of 80 mg/kg/d) according to umbilical swab finding. Omphalitis persisted for 10 days in spite of antibiotic therapy and only resolved upon the introduction of rhG-CSF therapy. Therapy with rh-GCSF proved efficient and led to neutrophil count increase to 1970/muL and cure of omphalitis. However, therapeutic effect on granulocyte count was of transient nature, as granulocyte count fell to 760 n/muL on day 4 of therapy discontinuation. Neutropenia persisted for 2 months. The newborn was discharged from the hospital on day 26 with normal clinical status with clinical and laboratory control examinations at 2-week intervals. No additional infections were observed during the course of neutropenia.
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PMID:A Case of Neonatal Neutropenia Due to Anti-Fc Gamma Receptor IIIb Isoantibodies Treated with Recombinant Human Granulocyte Colony Stimulating Factor. 1973 Jul 45

Neutropenia associated with Kawasaki Syndrome (KS) has been rarely reported, and the detailed mechanisms responsible for this state are not yet elucidated. The aim of this study was to clarify the mechanisms of neutropenia in KS. We examined antibodies to known neutrophil antigens (HNA1a, HNA1b, HNA null, HNA2, HNA3, HNA4 and non-HLA antigen 9a) in a KS patient with neutropenia. We also performed the granulocyte immunofluorescence test (GIFT) using patient or control neutrophils incubated with the patient's serum at serial time points over the patient's clinical course. No specific antibody to known neutrophil antigens was detected. Flow cytometric analysis showed that autoantibodies bound to immature CD13-positive myeloid cells, which resulted in myeloid lineage maturation arrest in the bone marrow. GIFT showed that neutrophil-specific autoantibodies were produced by the patient, and the amount of autoantibody inversely correlated with the patient's neutrophil counts. The presence of an autoantibody to a novel antigen on immature myeloid cells or neutrophils is the likely the cause of severe neutropenia in this patient with KS.
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PMID:Potential role of autoantibody in severe neutropenia of a patient with Kawasaki Syndrome. 2192 41

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

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) and neonatal alloimmune neutropenia (NAN) are two rare complications of newborns caused by antibodies against paternal inherited antigens. Human platelet (HPA) and neutrophil antigens (HNA) are the common targets. Human leukocyte antigen (HLA) class I proteins are also expressed on platelets and neutrophils and anti-HLA antibodies have occasionally been implicated in these complications. We report a premature twin infant who presented with severe thrombocytopenia and neutropenia clinically compatible with FNAIT and NAN, from a mother with no identifiable HPA or HNA antibodies, but with very high levels of complement-fixing antibodies against paternal inherited HLA. These antibodies were also detected in the infant. HLA antibodies are commonly present in multiparous women who deliver healthy infants. They can, however, be cytotoxic and cause clinical complications after blood products transfusion (TRALI and becoming refractory to platelets transfusion) and after organ transplantation (allogeneic organ rejection).
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PMID:Implication of antibodies against human leukocyte antigen in simultaneous presentation of fetal and neonatal alloimmune thrombocytopenia and neutropenia. 3031 77


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