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)

Evidence has been found to document the presence of circulating immune complexes in all patients with Felty's syndrome. The sera of all 12 patients studied showed intermediate complexes by analytical ultracentrifugation. The sera of 9 of 12 patients (75%) showed precipitin lines upon immunodiffusion against IgM rheumatoid factor. Both findings were statistically increased above those in a matched group of patients with classic rheumatoid arthritis. The presence of circulating immune complexes in the sera of the Felty patients was consistent with the observation that large inclusions containing IgG, IgM, and complement were phagocytized by normal polymorphonuclear cells when incubated with sera of Felty patients. Normal polymorphonuclear cells phagocytosed inclusions from 77% of Felty sera, compared with 27% classic rheumatoid arthritis sera. It is suggested that the uptake of immune complexes by polymorphonuclear cells plays a role in the neutropenia of Felty's syndrome.
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PMID:Comparison of the presence of immune complexes in Felty's syndrome and rheumatoid arthritis. 41 29

Sera from patients with Felty's syndrome (FS) and rheumatoid arthritis (RA) were examined for the presence of circulating immune complexes (IC) by using the 125I-C1q binding and monoclonal rheumatoid factor (mRF) techniques. Of 15 patients with FS, 9 (60%) had high 125I-C1q binding as compared to 3 of 26 RA patients (12%). The average C1q binding was significantly higher in the FS patients than in the RA patients without FS. C1q binding in both FS and RA patients was significantly higher than a group of 90 normal controls. In addition, serum C4 levels were significantly lower in the FS patients than in the RA patients. In contrast to these findings, IC levels in FS and RA patients were very similar when measured by the mRF technique. These studies indicate that FS patients have higher levels of complement-fixing IC in their sera than RA patients without FS. These findings raise the possibility that the complement-fixing IC found in these patients may play a role in the pathogenesis of neutropenia of FS.
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PMID:Increased C1q binding immune complexes in Felty's syndrome: comparison with uncomplicated rheumatoid arthritis. 45 98

Six cases of large granular T-cell lymphoproliferative disorder with a selected immunophenotype (CD3+, CD4-, CD8+, CD16+) were studied to characterize a homogeneous group of patients. It was found that most of these patients did not exhibit the clinical features frequently described in large granular T-cell lymphoproliferative disorder--recurrent infection, rheumatoid arthritis, and splenomegaly. The laboratory tests usually positive in large granular T-cell lymphoproliferative disorder, including rheumatoid factor and anti-nuclear antibodies, also were frequently negative. The pathognomonic features were found to be neutropenia and large granular lymphocytosis with positive killer cell markers. All six cases showed T-cell receptor gene rearrangement that indicated a monoclonal proliferation of lymphoid cells, which were natural killer-like T cells by immunophenotyping. B cells were essentially absent in all cases. It should be emphasized that bone marrow aspirates are as informative as peripheral blood samples for the diagnosis of large granular T-cell lymphoproliferative disorder; indeed, phenotypes of blood and marrow in one case were identical in terms of percentages of markers. In this selected group of patients, the clinical courses were indolent with uncomplicated outcomes. In three patients, chemotherapy did not induce an obvious clinical response, but all patients' conditions remained stable with only supportive care.
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PMID:Study of the major phenotype of large granular T-cell lymphoproliferative disorder. 821 44

Thirteen patients with expansion of an unusual subset of T lymphocytes, defined by large size, cytoplasmic granularity and CD3+ CD8+ Leu 7+ surface phenotype, are reported. Although morphologically and/or phenotypically abnormal lymphocytes were found in all patients, only five had an absolute peripheral blood lymphocytosis. Ten patients had a bone marrow lymphocytosis. As in previous series, there was a strong association with neutropenia (12 patients) and polyarthropathy (seven patients). The latter group displayed a wide range of articular disease: classical or definite rheumatoid arthritis in four patients and milder non-erosive disease in the remainder. All 13 patients showed evidence of abnormal B cell function: IgM rheumatoid factor was present in nine patients, neutrophil-specific antibodies in six and all showed an increased level of at least one immunoglobulin isotype. These patients may be difficult to distinguish from those with idiopathic neutropenia and Felty's syndrome. Such a distinction may not be made on clinical grounds alone: critical assessment of lymphocyte morphology, bone marrow examination and analysis of lymphocyte phenotype should be considered in all patients with unexplained neutropenia, particularly in the context of arthritis. It is suggested that the true prevalence of this syndrome may have been greatly underestimated.
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PMID:Large granular T lymphocytes, neutropenia and polyarthropathy: an underdiagnosed syndrome? 167 66

Thirty-two patients with the Felty syndrome, defined by the presence of rheumatoid arthritis, splenomegaly, and neutropenia, have been studied in comparison with 32 patients with rheumatoid arthritis matched for age, sex, and disease duration, and 9 patients with rheumatoid arthritis and idiopathic neutropenia. Patients with the Felty syndrome had severe destructive arthritis, which progressed during follow-up despite little evidence of objective synovitis, and a higher frequency of extra-articular manifestations, including vasculitis. Bacterial infection tended to occur in patients with the lowest neutrophil count but continued to occur in some despite normalization of the WBC. Prognosis was poor and 8 deaths occurred, predominantly from sepsis. Serologic features were prominent. High titers of IgG rheumatoid factor and circulating immune complexes characterized patients with persistent neutropenia. A family history of rheumatoid arthritis was more common in patients with the Felty syndrome. The association with HLA DR4 was very strong; in addition there was an increased frequency of the DQw3 variant, 3b, suggesting that HLA Class II genes in linkage with DR4 may contribute to disease expression.
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PMID:The Felty syndrome: a case-matched study of clinical manifestations and outcome, serologic features, and immunogenetic associations. 196 4

A young female patient who had documented seropositive rheumatoid arthritis and was treated consecutively with aspirin, diclofenac, and gold salts was admitted years later for severe neutropenia. On examination she had, in addition, fever, positive rheumatoid factor, reversible swan-neck deformity of the fingers but otherwise normal joint findings. The patient responded to prednisone therapy. This case would appear to be a most unusual variant of Felty's syndrome.
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PMID:Felty's syndrome without concomitant arthritis: a variant. 275 10

We prospectively evaluated the usefulness of measuring antineutrophil (PMN) antibodies in patients with neutropenia by a sensitive immunoassay. The result of the immunoassay were compared to a standard leukoagglutination test. Thirty-two patients with neutropenia were studied. The mean value (+/- 1 SD) for PMN-bound IgG for 43 normal controls was 121 +/- 29 fg/PHN. All fifteen patients with immune neutropenia had elevated plasma levels of anti-PMN antibody (191-2,000 fg/PMN). The leukoagglutination assay was positive in 10 of these 15 patients. In 17 patients with nonimmune neutropenia, the mean value (+/- 1 SD) for PMN-bound IgG was 120 +/- 22 fg. Seventeen patients with sero-positive rheumatoid arthritis but normal PMN counts were also studied. These patients' plasmas bound 447 +/- (1 SD) 201 fg IgG/PMN. The leukoagglutination test was negative in these patients. Our study shows that the immunoassay is more sensitive than leukoagglutination testing for diagnosing immune neutropenia. Nonimmune, neutropenic patients' plasmas showed no increased reactivity. In nonneutropenic patients who have high titers of rheumatoid factor, immunoreactivity against PMN is measured by the immunoassay, but not by leukoagglutination testing. Binding assays may be more sensitive than leukoagglutination testing for measuring anti-PMN antibodies; however, in some cases, specificity of such testing may be increased with leukoagglutination testing.
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PMID:The diagnostic usefulness of measuring antineutrophil antibodies in neutropenic patients. 309 Aug 24

LGL leukemia results from a chronic, clonal proliferation of LGL. Chronic neutropenia with recurrent bacterial infection and splenomegaly are common clinical manifestations. Rheumatoid arthritis coexists in some of these patients, who thus resemble patients with Felty syndrome. Other hematologic abnormalities that may occur include pure red-cell aplasia and adult-onset cyclic neutropenia. Lymphoid infiltration of bone marrow, splenic red pulp cords, and hepatic sinusoids is characteristic; lymph node and skin involvement are rare. Multiple serologic abnormalities are frequently present, including positive tests for rheumatoid factor and/or antinuclear antibody, polyclonal hypergammaglobulinemia, and circulating immune complexes. Antineutrophil and antiplatelet antibodies are often present. Leukemic LGL exhibit phenotypic heterogeneity; the most common phenotype in our patients is CD2+, CD3+, CD8+, HNK-1+, CD16-. Despite markedly increased numbers of LGL, functional activity of the cells is usually decreased. The mechanism of cytopenias is uncertain: in pure red-cell aplasia, it appears to be due to suppressive effect on erythropoiesis by abnormal LGL, but in patients with chronic neutropenia it may be antibody-mediated. Although most patients appear to have a relatively benign clinical course, mortality from infections and progressive lymphoproliferation is substantial. Optimal therapy remains undefined. Some preliminary evidence suggests that LGL leukemia may be associated with infection with a retrovirus similar to HTLV-I. Although relatively rare, LGL leukemia is of interest because a better understanding of this disease process may contribute to our knowledge of autoimmune diseases, the immunoregulatory functions of LGL, and the mechanisms controlling normal hematopoiesis.
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PMID:Large granular lymphocyte leukemia. Report of 38 cases and review of the literature. 362 48

Three patients had leukocytosis of large granular lymphocytes and chronic neutropenia. Clonal chromosomal abnormalities (trisomy 8 and trisomy 14) and lymphocytic infiltration of splenic red pulp, hepatic sinusoids, and bone marrow indicated the neoplastic nature of the large granular lymphocytes. Demonstration of a T3+, T8+, HNK-1 + phenotype and low natural killer cell activity that was augmented by interferon treatment showed the leukemic cells to be immature natural killer cells. Multiple autoantibodies were present and included rheumatoid factor and antinuclear, antineutrophil, antiplatelet, and antierythrocyte antibodies, suggesting a defect of B-cell immunoregulation. In addition, in-vitro studies showed impaired suppression of immunoglobulin biosynthesis by abnormal cells from one patient. Antineutrophil antibodies and absence of direct cell-mediated inhibition of granulocyte-macrophage colony formation supported a humoral immune mechanism for the neutropenia. In these patients the syndrome of splenomegaly, multiple autoantibodies with neutropenia, and lymphocytosis of large granular lymphocytes is due to a neoplastic proliferation of immature natural killer cells.
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PMID:Leukemia of large granular lymphocytes: association with clonal chromosomal abnormalities and autoimmune neutropenia, thrombocytopenia, and hemolytic anemia. 396 54

Five patients with polyarthritis and neutropenia had numerous circulating large granular lymphocytes with a phenotype attributed to immature natural killer cells. All five had splenomegaly and recurrent infections. Arthritis was most prominent at the wrists and hands, and all patients were considered to have atypical cases of Felty's syndrome. Antinuclear antibodies, rheumatoid factor, antineutrophil antibodies, and immune complexes were detected in most patients. Bone marrow biopsies revealed a maturation arrest at the myelocyte stage and lymphoid infiltrates. Large lymphocytes with azurophilic cytoplasmic granules were found on peripheral blood smears and showed a characteristic reactivity pattern with monoclonal antibodies suggesting a natural killer cell lineage. Peripheral blood mononuclear cells showed less than normal natural killer activity against K562 target cells. Increased numbers of large granular lymphocytes with a phenotype of immature natural killer cells may be important in the pathogenesis of neutropenia, humoral immune disturbances, and synovitis in a subset of patients with Felty's syndrome.
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PMID:Polyarthritis and neutropenia associated with circulating large granular lymphocytes. 402 84


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