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

The sera of three children with chronic benign neutropenia, due to anti-neutrophil antibodies, were studied with respect to their antibody specificity. This was done by screening the sera against a panel of leukocyte donors in the EDTA micro-agglutination test and in the indirect fluorescence test. Two of the sera contained antibodies against the known neutrophil-specific antigen NA2. The third serum was directed against a new neutrophil-specific antigen. Genetic analysis showed no correlation between this antigen and the already known neutrophil-specific antigens: 9A, NA1, NA2, NB1, and NC1. In the Dutch population the frequency of the new antigen, tentatively called NE1, is 23%, which gives a gene frequency of 0.12.
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PMID:NE1: a new neutrophil specific antigen. 8 23

Neutrophil antigens may be classified into two major categories: antigens shared with other cells and antigens specific for neutrophils. The first category includes the ABH, I, i, 5a,b and HLA determinants. Additional antigens with special characteristics in this category are the blood-group U, Kx, JkaJkb, and Ge determinants which apparently neutrophils share only with erythrocytes. Neutrophil-specific antigens include the NA1, NA2, NB1 and 9a. These specificities are detected by the agglutination test and have been shown to be present on mature neutrophils. Independent allospecificities, detectable by the granulocytotoxicity test, may also exist. In addition, neutrophil antigens, which are species-specific, have been identified by the use of xenogeneic antibodies. The EDTA-dependent agglutination test remains a most reliable assay for the study of neutrophil-specific antigens. The lack of reproducibility known in the leukoagglutination reaction does not pertain to the modification used in the assay of neutrophil-specific antibodies. It does apply, however, to those tests that were performed in the absence of EDTA, and in connection to the study of HLA-related antigens. For every pathophysiological state involving the erythrocyte antigens a neutrophil analogue is observed, the difference being in symptomatology which is related to the structural and functional characteristics of the cells: febrile and pulmonary transfusion reactions result from incompatibility neutrophils. It is found that similarity in the HLA antigens and nonreactivity in the MLC test do not preclude immunization against neutrophil-specific antigens. Therefore, it is probable that febrile and pulmonary reactions will occur in the recipients of multiple granulocyte transfusions, even though donors and recipients may be considered "histocompatible" by the HLA assays. It has been shown that fetal-maternal incompatibility can cause neonatal neutropenia, and several forms of autoimmune neutropenia are described: in "idiopathic" neutropenia of infancy, autoantibodies have been found to have specificity against NA1 and NA2 and in one adult, autoimmune neutropenia due to anti-NA1 antibody has been observed. Neutropenia also occurs due to idiopathic, cold-reacting antileukocyte antibodies, and with cold agglutinins associated with lymphoma, infectious mononucleosis, and Mycoplasma pneumonia. Although the role of neutrophil antigens in bone marrow transplantation has not as yet been determined, these antigens are undoubtedly immunogenic and potentially play an important role in neutrophil compatibility. It is obvious that neutrophils cannot survive in the presence of antineutrophil antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neutrophil antigens: immunology and clinical implications. 40 Jul 55

Postpartum sera of 1,016 unselected women were examined for granulocyte-specific and HLA antibodies. A total of 11 out of 1,016 sera (1.1%) were only reactive with neutrophils. Cytotoxic HLA antibodies were detected in 24%, noncytotoxic HLA antibodies in 4.8% of the sera. All antibodies belonged to the IgG 1 and IgG 3 subclasses. NA1 and NB1 specificity were each determined in one serum, two sera contained NA2-specific antibodies. After 1 year all antibodies were no more detectable. As none of the newborns from immunized mothers developed neutropenia, the incidence of alloimmune neonatal neutropenia seems to be lower than 0.1%.
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PMID:[Granulocyte-specific and HLA antibodies in pregnancy: incidence and clinical value]. 128 57

Eighteen cases of alloimmune neonatal neutropenia (ANN) were analysed for their clinical and serological properties. Pregnancy was normal in all cases, but a 50% incidence of abortion is recorded. With the exception of two premature babies, all newborns were delivered at term. Omphalitis and mild infections of the skin were predominantly present. None of the new-borns died by overwhelming sepsis. The average duration of neutropenia was 11 weeks (range 3-28 weeks). Intravenous IgG therapy was followed by transient remission in 2 of 4 affected newborns. Antibody differentiation revealed in five sera NA1-, in four sera NA2- and in two sera NB1-specific antibodies. In two sera only HLA antibodies were detectable. Complement activating antibodies were determined in 72% of the sera. Screening for granulocyte-specific antibodies in 1016 postpartum sera of unselected women revealed a total of 11 sera (1.1%) reacting selectively with granulocytes, but only four (0.4%) were directed against a known granulocyte-specific antigen. None of the new-born of mothers alloimmunized to granulocyte antigens developed neutropenia, which suggests an incidence of ANN below 0.1%.
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PMID:Serological and clinical aspects of granulocyte antibodies leading to alloimmune neonatal neutropenia. 128 78

Neutrophil-specific alloantibodies and the antigens they recognize are important in clinical medicine but little is known about the structure of these antigens. Alloimmunization to the antigen NB1 is a clinically important cause of neonatal neutropenia and leukocyte-mediated transfusion reactions. A novel mechanism of protein attachment to cell membranes involving the covalent linkage of the protein through an oligosaccharide to phosphatidylinositol has recently been defined. Many proteins which are anchored to the cell membrane by this mechanism can be released by treatment with phosphatidylinositol-specific phospholipase C (PI-PLC). The 58-64-kDa human neutrophil surface protein which contains the NB1 antigen was labeled with 125I by using lactoperoxidase and examined for PI-PLC sensitivity. The 58-64-kDa protein was specifically released from the cell by treatment with PI-PLC, and the mobility of the protein under non-denaturing conditions using non-ionic detergent was increased by treatment with PI-PLC. Surface expression of the NB1 antigen was slightly up-regulated by treatment with the chemotactic peptide f-met-leu-phe. Removal of N-linked carbohydrates with endoglycosidase-F decreased the apparent molecular weight of the protein to approximately 45-kDa. The data suggest that most of the 58-64-kDa protein bearing the neutrophil-specific antigen NB1 is anchored to the membrane through a glycosyl-phosphatidylinositol linkage.
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PMID:Neutrophil-specific antigen NB1 is anchored via a glycosyl-phosphatidylinositol linkage. 182 10

Neutrophil-specific alloantibodies and the antigens they recognize are important in clinical medicine, but little is known about the structure of these antigens. Alloimmunization to the antigen NB1 is a clinically important cause of neonatal neutropenia and febrile transfusion reactions. To study the immunochemistry of the NB1 antigen, we prepared neutrophil plasma membranes and granules by nitrogen cavitation and differential centrifugation and then analyzed them by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting with alloantibodies to several neutrophil-specific antigens. Two different antisera to the neutrophil-specific antigen NB1 identified an approximately 55-Kd protein by immunoblotting on neutrophil membranes from four NB1-positive donors but not on neutrophil membranes from five NB1-negative donors. Four anti-NB1 antisera immunoprecipitated a 58- to 64-Kd protein from extracts of NB1-positive neutrophils surface-labeled with 125I using lactoperoxidase, but not from similarly treated NB1-negative neutrophils. Normal human serum did not immunoprecipitate or immunoblot any proteins from these same neutrophil preparations. The NB1 antigen was detected by immunoblotting in secondary granules but was not found in primary granules. The electrophoretic mobility of the antigen was decreased slightly by reduction, suggesting that intrachain disulfide bonds were present. After reduction, the antigen could no longer be recognized by anti-NB1 antisera, but treatment of the antigen with periodate had no effect on the ability of anti-NB1 antisera to recognize the antigen, suggesting that it is not a carbohydrate. The data suggest that the neutrophil-specific antigen NB1 is present on a 58- to 64-Kd surface glycoprotein that is also present in secondary granules, and that the NB1 epitope is not a carbohydrate but probably resides in the tertiary structure of the protein backbone.
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PMID:Biochemical characterization of the neutrophil-specific antigen NB1. 215 25

Neutrophil specific antigens (NA) are expressed exclusively on human neutrophils and were identified using alloantibodies. Neutrophil specific antigens are polymorphic, and several of them (NA1, NA2, NB1, NB2, NC1, ND1, NE1, and 9A), are thought to define genes at different loci. Feto-maternal incompatibility of NA has resulted in alloimmune neonatal neutropenia. Also, NA are the target antigens for autoantibody production in infants and young children with autoimmune neutropenia of infancy and chronic idiopathic neutropenia in adults. Autoimmune neutropenia can occur secondary to several other diseases, including AIDS. Numerous assays are useful in detecting granulocyte antibodies in patients with neutropenia. Among these assays, granulocyte agglutination (GA) and granulocyte immunofluorescence (GIF) are available in some clinical laboratories. Both IgG and IgM agglutinins are detected by GA: in addition, IgG, IgM, and IgA are detected by GIF. Immune neutropenia (IN) occurs in all age groups. Originally thought to be rare, IN is being increasingly recognized in recent years. Further investigations should lead to a greater understanding of the role of NA in immune neutropenias and to identify as yet unknown NA specificities. With the availability of reproducible and sensitive assays to detect granulocyte antibodies and the increasing knowledge and understanding of various disease aspects of IN, proper diagnosis and appropriate clinical management are being applied.
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PMID:Neutrophil antigens and antibodies in the diagnosis of immune neutropenias. 265 24

Neutrophil agglutinins that caused primary autoimmune neutropenia in six young children less than two years of age reported earlier were investigated further for antibody identification and specificity using granulocyte agglutination technique. Initially, the patient sera were tested with parental neutrophils and further confirmed with several donor cells. The sera were tested with autologous neutrophils after partial or complete recovery of the patients from neutropenia. The pattern of reactivity of the patient sera with parental, donor, or autologous neutrophils was compared with that of standard neutrophil typing sera currently available for the antigens NA1, NA2, NB1, NC1, and 9A. The specificity was confirmed by absorbing and retesting the sera with appropriate antigen positive and negative donor neutrophils. Our data revealed anti-NA1 specificity in four and anti-NA2 in two sera. Our observations together with that of McCullough et al suggest that NA1 and NA2 antigens are frequently associated with primary AINI in young children as compared to other neutrophil antigens.
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PMID:Characterization of neutrophil agglutinins in primary autoimmune neutropenia of early childhood. 305 43

Antiviral agents under investigation for the treatment of patients infected with the human immunodeficiency virus (HIV) are reviewed. Multiple mechanisms exist by which antiviral agents might inhibit the replication of HIV or eradicate its latent form in affected cells, or both. These mechanisms include (1) interference with the cell surface receptor for HIV, (2) prevention of uncoating of viral particles, (3) inhibition of reverse transcriptase, (4) prevention of integration and posttranscription processing, (5) interference with viral assembly, and (6) interference with virus release. Most agents developed thus far work by inhibiting HIV reverse transcriptase. Suramin, ribavirin, ammonium 21-tungsten-9-antimoniate (HPA-23), foscarnet (phosphonoformate, PFA), inosine pranobex (isoprinosine), peptide T, ampligen, AL 721, dideoxycytidine, and zidovudine (formerly azidothymidine) have antiretroviral activity in vitro. To date zidovudine is the only antiretroviral agent approved by the FDA as clinically effective. However, zidovudine has serious toxicities, including neutropenia and anemia; in some patients dosage reduction or cessation of therapy may be necessary. Because treatment with zidovudine does not cure HIV infection, numerous studies are under way with other anti-HIV agents. Ultimately, combinations of agents probably will be used to suppress or eradicate HIV. While the search for more efficacious and less toxic treatments continues, the development of zidovudine in such a short time provides hope that progress toward a cure will be made rapidly.
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PMID:Development of antiviral agents for the treatment of human immunodeficiency virus infection. 332 38

Three sera containing antibodies recognizing a previously undescribed antigen on granulocytes were found during testing of sera from multiparous donors. All of the antibody producers were in good health. None had a history of transfusion. Using the granulocyte agglutination assay the sera recognize a single antigen which is not associated with the neutrophil antigens NA1, NA2, NB1, NC1, ND1, NE1, 5a, 5b, 9a, nor common red blood cell or HLA antigens. The three sera did not react with autologous cells or with the cells of the other antibody producers. Granulocytes from one antibody producer did not absorb antibody activity from any of the three sera. The antigen was found in large quantities on granulocytes and monocytes, in smaller quantities on T lymphocytes, and not on B lymphocytes, red cells, and platelets. The sera reacted with 340 of 343 random donors (99.1%) and were negative with the same donor cells. Family studies showed autosomal dominant inheritance of the antigen. Five of 12 sibs in three families lacked this antigen (not statistically different from the expected ratio). The calculated gene frequency for the gene controlling the production of this antigen is 0.906. There appeared to be no association to the HLA, NA or Rh loci or to the X or Y chromosomes. None of the infants of these three women showed clinical signs of alloimmune neonatal neutropenia.
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PMID:Three sera defining a new granulocyte-monocyte-T-lymphocyte antigen. 352 Oct 82


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