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)

Fc gamma receptors are a group of three different receptors with several subtypes. They are widely distributed on many cells of the immune system and contribute to the pathogenesis of immune complex- and autoantibody-mediated diseases such as vasculitis, rheumatoid arthritis, idiopathic thrombocytopenic purpura or autoimmune neutropenia. This review focuses on the structure, distribution and function in Fc gamma receptors and their subtypes.
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PMID:[Fc gamma receptors: structure, function, and clinical significance]. 138 31

The chemiluminescent (CL) response of interferon-gamma-treated U937 (IFN-U937) cells to sensitized target cells has been used to detect red cell, platelet and granulocyte antibodies. A clone of U937 cells was selected which expressed Fc receptor I (Fc gamma RI) and which, after incubation with IFN-gamma for 72 h, was capable of generating high levels of lucigenin-enhanced CL. The CL responses of IFN-U937 cells and peripheral blood human monocytes to sensitized red cells, platelets or granulocytes were then compared. Assays using monocytes or IFN-U937 cells were of comparable sensitivity for detection of antibodies against all three types of target cell. In addition, the use of IFN-U937 cells reduced interassay variation and simplified assay performance. The potential clinical usefulness of these CL assays was suggested by the ability of both monocytes and IFN-U937 cells to respond to red cells, platelets or granulocytes sensitized with sera from pregnant women whose babies had either haemolytic disease of the newborn (HDN), alloimmune thrombocytopenia or alloimmune neutropenia respectively. In addition, monocytes and IFN-U937 cells both responded to red cells sensitized with antibodies against a variety of specificities of assumed (although not documented) clinical significance for blood transfusion recipients. In contrast, monocytes and IFN-U937 cells responded only weakly to red cells sensitized with either anti-D in sera from mothers of babies unaffected by HDN, or with antisera containing high titre antibodies with specificities not normally associated with significantly reduced red cell survival.
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PMID:The use of interferon-gamma-treated U937 cells in chemiluminescence assays to detect red cell, platelet and granulocyte antibodies of potential clinical significance. 147 11

We report the case of a healthy woman (K.M.) who, after multiple pregnancies, developed an antibody directed against a nonpolymorphic region of the polymorphonuclear neutrophil (PMN) Fc gamma receptor III (FcRIII-CD16), which caused transient neonatal alloimmune neutropenia (NAIN). The antigenic target of the antibody was determined by an immunoprecipitation procedure and by phenotyping the mother's PMN. These latter did not react with monoclonal CD16 or polyclonal and monoclonal NA1 and NA2 antibodies, demonstrating the absence of PMN-FcRIII and, consequently, the NA-null phenotype. We also determined the frequency of the NA-null phenotype in a healthy, white population. Among 3,377 random blood donors, only four (in addition to K.M.) were PMN-FcRIII-deficient. These five individuals were healthy and only one (K.M.) presented an allo-CD16 antibody. The gene frequency of the NA-null phenotype was calculated as 0.0274 +/- 0.0059. We conclude that PMN-FcRIII deficiency is a rare phenomenon that can lead to CD16 alloimmunization and thus cause NAIN.
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PMID:Frequency of the polymorphonuclear neutrophil Fc gamma receptor III deficiency in the French population and its involvement in the development of neonatal alloimmune neutropenia. 153 16

Mononuclear cells expressing Fc gamma receptors that form Facb rosettes are increased in the peripheral blood of patients with rheumatoid arthritis compared with controls. Healthy individuals with a positive skin response to tuberculin showed a marked increase in numbers of circulating Facb-R+ cells three days after challenge, returning to baseline after seven days. No response was observed in subjects showing a negative skin test. A similar increase in Facb-R+ cell numbers was measured after intramuscular injection of another specific antigen, tetanus toxoid. In addition to this enhancement of Facb-R+ cell numbers, evidence has been obtained that these cells are in an activated state postimmunisation as judged by acquisition of low density and increased expression of class II MHC antigens. Apparently identical changes in Facb-R+ cell numbers and activation may be induced in vitro either by culturing sensitised mononuclear cells with specific antigen for three days or by an overnight incubation of normal cells with gamma-interferon (gamma-IFN). By analogy, therefore, the increased numbers of Facb-R+ cells in patients with rheumatoid arthritis are probably induced by gamma-interferon generated as part of an antigen driven immune response. In this context it is interesting that patients with Felty's syndrome, in whom neutropenia increases susceptibility to infections leading to the possibility of further stimulation of the immune system by micro-organisms, have particularly high levels of circulating Facb-R+ cells.
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PMID:Lymphocytes bearing Fc gamma receptors in rheumatoid arthritis. IV. Increased numbers and activation of Facb-R+ cells after immunisation of healthy individuals. 309 96

A 33-year-old female with cyclical neutropenia and a reciprocally cycling T8 (suppressor/cytotoxic) lymphocytosis was investigated. T8 lymphocytes ranged between 1.4 and 5.6 X 10(9)/l and a significant proportion (50-75%) were preactivated (1a+). Fc gamma receptors were detected in only a minority (7-10%). Functional studies on the lymphocytes indicated that despite their phenotype, little natural killer and reduced suppressor activities were present. Anti-granulocyte antibodies were not detectable in the serum. Production of colony stimulating activity (CSA) was assessed in the patient and control subjects' lymphocytes. Using a methylcellulose marrow culture system, the CSA production by the patient's lymphocytes was markedly increased compared with the control. Monoclonal antibody cytotoxic experiments confirmed that the T8 lymphocytes were responsible. As peaks of circulating T8 lymphocytes were synchronous with granulopoietic activity in the marrow, the above findings may represent a homeostatic mechanism which is attempting to compensate for an underlying stem cell defect.
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PMID:Cyclical neutropenia and T8 lymphocyte mediated stimulation of granulopoiesis. 316 Mar 83

The expanded T cell populations of 10 patients with either T gamma lymphocytosis (five patients) or proven chronic T cell malignancy (five patients) were analyzed with respect to functional activity in vitro, including proliferative responses to mitogens, cytotoxic activity (killer [K] and natural killer [NK] cell activity), and regulatory activity on pokeweed mitogen- (PWM) induced immunoglobulin (Ig) synthesis (help and suppression) in comparison with marker phenotypes. In each of the five patients with T gamma lymphocytosis, only one out of three functionally distinct cell types was found: T gamma-K cells, T gamma-S cells, or T gamma-NK/K cells, which mediated K-cell activity, suppressive activity, and both NK and K cell activity, respectively. An expanded T gamma-K cell population was demonstrated in three patients with neutropenia with or without recurrent infections. T gamma-S cells were found in a patient with severe hypogammaglobulinemia, and T gamma-NK/K cells in one patient with asymptomatic lymphocytosis. T gamma-K and T gamma-S cells had a similar surface-marker profile (E+ or E-, Fc gamma+, OKT1-3+4-8+I1-M1-), whereas that of T gamma-NK/K cells was different (E+, Fc gamma+, OKT1-3-4-8-I1+M1+). Longitudinal studies of three untreated patients with T gamma-K lymphocytosis showed that the abnormalities were persistent but not progressive. In contrast, five patients with chronic T cell malignancy (two with T-CLL, two with cutaneous T cell lymphoma [CTCL], and one with T-PLL) all had progressive disease. The neoplastic cells in these cases were E+, Fc gamma-OKT1+4+6- with variable expression of the OKT3 and OKT8 markers. The only functional activity observed in these cells was suppressive activity by OKT3-4+8- cells from a patient with CTCL.
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PMID:Functional properties of T cells in patients with chronic T gamma lymphocytosis and chronic T cell neoplasia. 621 84

A group of patients with neutropenia or erythroid aplasia associated with T cell proliferation were evaluated to assess the phenotype(s) and functions of T cells observed in these conditions. These patients have near normal numbers of helper/inducer cells but an excess of cells belonging to the suppressor/cytotoxic subset. The characteristic phenotype of these cells is E+, OKT3+, OKT1+1-, OKT8+, Fc gamma R+, and they frequently bear HLA-DR antigen. These cells respond poorly to T cell mitogens and will suppress the response of normal peripheral blood mononuclear cells to mitogens. They fail to suppress PWM-induced immunoglobulin synthesis. Although the natural killer activity in these patients is sometimes low, this subset of T cells possesses cytotoxic capability demonstrable in assays for antibody-dependent cell-mediated cytotoxicity. The evidence for a direct effect of the T cells on BFUE and CFUGM is poor.
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PMID:Cytopenia and T cell proliferation. 621 25

A case of T cell chronic lymphocytic leukaemia (CLL) with red cell hypoplasia and neutropenia is reported. WBC was 10.0 X 10(9)/l with 78% being T lymphocytes. These T lymphocytes were positive for Fc gamma receptor and had OKT8 and Leu 2a antigens on the cell surfaces. They suppressed both erythroid and granulocyte-macrophage colony formation in normal bone marrow cultures and suppressed immunoglobulin production by normal B lymphocytes in vitro. Though the myeloid cells were preserved in the bone marrow and the values of serum immunoglobulins were within normal limits, it can be estimated from these results that red cell hypoplasia and neutropenia were partially due to the suppression of haemopoietic precursor cells by leukaemic T lymphocytes.
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PMID:Suppressor T cell chronic lymphocytic leukaemia associated with red cell hypoplasia. 623 67

With the purpose of detecting granulocyte-specific membrane-directed autoantibodies, IgG was isolated from 14 patients with Felty's syndrome, from 5 patients with rheumatoid arthritis associated with neutropenia, and from 3 rheumatoid factor positive patients with autoimmune neutropenia. By means of indirect immunofluorescence suspensions of leukocytes from healthy controls were tested for their ability to bind whole IgG fractions or F(ab')2 fragments of IgG isolated from the neutropenic patients. By this method, whole IgG preparations from neutropenic patients and normal controls were invariably found to bind to the surface of granulocytes and a minor proportion of lymphocytes. In contrast. F(ab')2 fragments of IgG from the neutropenic patients failed to bind to the surface of granulocytes. Both whole IgG fractions and F(ab')2 fragments displayed displayed antinuclear antibody activity ruling out the possibility of loss of antibody reactivity during the preparation of F(ab')2 fragments. The neutropenia seen in rheumatoid arthritis with or without splenomegaly thus does not seem to be induced by granulocyte-specific membrane-directed IgG autoantibodies, but rather by a non-specific attachment of IgG most probably in immune complex bound form to Fc gamma receptors on neutrophils which thereby acquire surface properties facilitating removal from the circulating blood cell pool.
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PMID:Lack of evidence for granulocyte specific membrane-directed autoantibodies in neutropenic cases of rheumatoid arthritis and in autoimmune neutropenia. 634 99

A 67-year-old man with stable chronic neutropenia, lymphocytosis, multiple auto-antibodies, and recurring infections was studied in order to characterize the abnormal lymphocytes and the mechanism of neutropenia. One-half of the circulating mononuclear leukocytes were large granular lymphocytes that did not rosette with sheep erythrocytes and did not have surface immunoglobulin or receptors for C3 or IgG Fc. Virtually all of the mononuclear leukocytes, however, reacted with three monoclonal antibodies specific for mature T lymphocytes--OKT3, 3A1, and 12.1--the latter with a bimodal pattern on FACS analysis. The nonadherent, non-E-rosetting lymphocytes consisted of a homogeneous population of T cells with a novel phenotype: 3A1+, OKT3+, OKT8+, Ia+, 12.1+, OKT4-, 9.6-, 10.2-, Fc gamma receptor-. The abnormal phenotype of these cells suggested that they may have developed clonally. In spite of their OKT8+ phenotype, these lymphocytes were functionally abnormal, since they did not suppress B-cell immunoglobulin production in vitro. A humoral immune mechanism of neutropenia was indicated by increased levels of neutrophil-reactive IgG and in vivo kinetic studies with autologous neutrophils demonstrating shortened intravascular survival. The granulocyte turnover was normal, however, suggesting a blunted marrow response to the neutropenia. Corroborating the kinetic data, in vitro cultures of the patient's blood and marrow cells showed reduced numbers of granulocytic progenitors (CFU-C). Neither blood lymphocytes nor serum from the patient suppressed growth of allogeneic CFU-C nor did removal of OKT8+ cells from the marrow increase CFU-C expression. Thus, the disorder in this patient is characterized by proliferation of abnormal OKT8+ lymphocytes with impaired suppressor function. Our findings suggest that the neutropenia was due to anti-neutrophil autoantibodies that may have resulted from abnormal T-cell immunoregulation.
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PMID:Chronic lymphocytosis with neutropenia: evidence for a novel, abnormal T-cell population associated with antibody-mediated neutrophil destruction. 660 12


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