Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD43 (leukosialin, gpL115, sialophorin) is a major sialoglycoprotein widely expressed on hematopoietic cells that is defective in the congenital immunodeficiency Wiskott-Aldrich syndrome. It is thought to play an important role in cell-cell interactions and to be a costimulatory molecule for T lymphocyte activation. Using a metabolic 35SO4(2-) radiolabeling assay or biotinylation of cell surface proteins, we describe here that CD43 are sulfated molecules the glycosylation of which is altered in human immunodeficiency virus type 1 (HIV-1)-infected leukemic T cells of the CEM line. Hyposialylation of O-glycans and changed substitution on N-acetylgalactosamine residues are observed. The glycosylation defect is associated with an impairment of CD43-mediated homotypic aggregation which can be restored by resialylation. The hyposialylation of CD43 on HIV-1+ cells may explain the high prevalence of autoantibodies directed against nonsialylated CD43 that have been detected in HIV-1-infected individuals. A defect in glycosylation of important molecules such as CD43 or, as we recently described, CD45 may explain alterations of T cell functions and viability in HIV-1-infected individuals. In addition, a possible implication of hyposialylation in the HIV-1-infected cells entrapment in lymph nodes could be envisioned.
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PMID:Altered glycosylation of leukosialin, CD43, in HIV-1-infected cells of the CEM line. 796 49

The Wiskott-Aldrich syndrome (WAS) is associated with defective glycosylation and altered membrane expression of the leukocyte sialoglycoprotein CD43. To investigate whether such modifications of CD43 are relevant to T cell dysfunction in WAS, we have analyzed peripheral blood mononuclear cells from WAS patients for proliferative responses to both CD43-interacting and other T cell mitogenic stimuli. While patient lymphocytes proliferated in response to phytohaemagglutinin, concanavalin A, interleukin-2 and neuraminidase/galactose oxidase, no responses were elicited upon attempted triggering of the CD43 signalling pathway using periodate or anti-CD43 antibody. Cells from four of five patients with clinical profiles resembling, but not identical, to that of classic WAS also failed to respond to periodate or anti-CD43 antibody stimulation. These results indicate that the aberrant expression of CD43 on WAS lymphocytes is associated with selective impairment of CD43-induced T cell proliferation and that detection of this defect may be useful in the diagnosis of WAS and its variant forms.
Immunodeficiency 1993
PMID:Selective impairment of CD43-mediated T cell activation in the Wiskott-Aldrich syndrome. 816 44

We report two sisters in a family representing manifestations of Wiskott-Aldrich syndrome (WAS), an X-linked immunodeficiency disorder. An elder sister had suffered from recurrent infections, small thrombocytopenic petechiae, purpura, and eczema for 7 years. The younger sister had the same manifestations as the elder sister's for a 2-year period, and died of intracranial bleeding at age 2 years. All the laboratory data of the two patients were compatible with WAS, although they were females. Sialophorin analysis with the selective radioactive labeling method of this protein revealed that in the elder sister a 115-KD band that should be specific for sialophorin was reduced in quantity, and instead an additional 135-KD fragment was present as a main band. Polymerase chain reaction (PCR) analysis of the sialophorin gene and single-strand conformation polymorphism (SSCP) analysis of the PCR product demonstrated that there were no detectable size-change nor electrophoretic mobility change in the DNA from both patients. The results indicated that their sialophorin gene structure might be normal. Studies on the mother-daughter transmission of X chromosome using a pERT84-MaeIII polymorphic marker mapped at Xp21 and HPRT gene polymorphism at Xq26 suggested that each sister had inherited a different X chromosome from the mother. Two explanations are plausible for the occurrence of the WAS in our patients: the WAS in the patients is attributable to an autosomal gene mutation which may regulate the sialophorin gene expression through the WAS gene, or, alternatively, the condition in this family is an autosomal recessive disorder separated etiologically from the X-linked WAS.
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PMID:Two sisters with clinical diagnosis of Wiskott-Aldrich syndrome: is the condition in the family autosomal recessive? 912 30

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder originally described as a clinical triad of thrombocytopenia with small platelets, eczema, and immunodeficiency. Impaired CD43 glycoprotein expression on lymphocytes is a typical hallmark of this disorder. The CD43 gene is located on chromosome 16, and the WAS gene, WASP, was recently isolated from the chromosome X p11.22-p11.23. This gene, mutated in WAS patients, encodes a protein that is likely to play a role in controlling the expression of CD43. However, the molecular mechanism(s) causing WAS are not yet known. Herein, we describe a three-generation family in which clinical and laboratory WAS features were expressed in six of nine subjects available for study. At variance with classic X-linked WAS, this disorder was characterized by the presence of thrombocytopenia with a broad spectrum of platelet size, including giant platelets, and was inherited as an autosomal dominant trait. This last finding led us to hypothesize a mutation of the CD43 gene. However, Southern blot analysis failed to detect structural abnormalities of this gene, and genotype analysis ruled out the possibility that a CD43 allele might be shared by the affected individuals. These findings indicate that an alteration(s) of an autosomal gene distinct from the CD43 gene is responsible for the disease. Thus, results from this family, providing the first observation of an autosomally transmitted WAS variant, indicate that genetic mechanism(s) leading to WAS are more complex than previously recognized.
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PMID:Wiskott-Aldrich syndrome: report of an autosomal dominant variant. 863 21

This study compares the histologic and immunophenotypic features of 71 cases of primary CD30+ diffuse large-cell lymphomas (DLCL) and 128 cases of Hodgkin's disease (HD) and discusses the clinical features of 52 patients with CD30+ DLCL. It includes analysis of sites of involvement, staging, response to treatment, sites and treatment of recurrences, and disease-free and overall survival. Diagnostic immunophenotypic differences were found between CD30+ DLCL and HD. All cases of CD30+ DLCL were positive for one or more common or lineage-specific lymphocyte antigens or for EMA. In contrast, 96.9% of HD cases were negative for CD45, CD45-RO, CD43, and CD20. The four exceptions are discussed. All cases of HD were negative for EMA. In patients with CD30+ DLCL, a T-cell phenotype was found in 60%, a null-cell type in 22%, and a B-cell type in 18% of the cases. The median age of patients with T- and null-cell phenotype was 22 years (range, 4 to 72). Fifty-two percent of them had high-stage (III and IV) disease and 61% had extranodal involvement at presentation, including 25% with skin lesions. Lymph nodes draining the skin lesions became involved in seven of 11 patients. No patient had initial bone marrow involvement. Most patients were treated with chemotherapy, and 83% had a complete remission. Fifty-four percent remain free of disease with a median follow-up of 47 months. Thirteen patients (29%) had one or more recurrences and five of them remain free of disease after salvage therapy, with a median follow-up period of 79 months. The clinical stage did not affect survival, probably as a result of different therapy. The t(2;5) translocation was found in five of 15 patients who had cytogenetic abnormalities. Of the other 10 cases, the translocation was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in four of five cases studied. All nine cases were of T- or null-cell phenotype. The cases of B-cell CD30+ DLCL had a characteristic immunophenotype. All were negative for EMA. These patients were older and had frequent bone marrow involvement but no skin infiltration by lymphoma. All three patients who were human immunodeficiency virus-positive (HIV+) had lymphomas of B-cell lineage. Detection of the t(2;5) translocation by molecular genetics is a useful and highly specific marker in the differential diagnosis between HD and CD30+ DLCL.
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PMID:CD30 (Ki-1)-positive malignant lymphomas: clinical, immunophenotypic, histologic, and genetic characteristics and differences with Hodgkin's disease. 863 11

Chronic active Epstein-Barr virus infection (CAEBV) is a nonfamilial syndrome that shows a specific immunodeficiency for the Epstein-Barr virus (EBV). Prolonged fever, hepatosplenomegaly, lymphadenopathy, and liver dysfunction were seen in CAEBV, but cardiac complications are rare. An autopsy case of CAEBV with giant coronary aneurysms and aortic aneurysms is reported. The patient was a 5-year-old Japanese girl. At autopsy, the heart weighed 110 g, and bilateral coronary aneurysms were found. Microscopic studies revealed lymphoid vasculitis of coronary arteries, coronary venules, and aortic arteries. Immunohistochemically, infiltrating small lymphocytes were positive for CD3, CD45RO(UCHL-1), CD43(DF-T1). The presence of EBV in most of these T lymphocytes was proven by in situ hybridization using an EBV-encoded RNA-1 (EBER1) probe. To the best of the author's knowledge, pathology of aneurysms caused by lymphoid vasculitis in CAEBV has not been reported until now.
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PMID:Chronic active Epstein-Barr virus infection with giant coronary aneurysms. 865 48

Leukosialin (CD43 or sialophorin) is a cell surface sialoglycoprotein implicated in cell adhesion and proliferation whose tightly regulated expression in B lymphocytes is likely important for their normal development and/or function. To examine the physiologic role of mouse CD43 (mCD43) in vivo, we exploited transgenic (TG) mice whose developmental expression of mCD43 was extended during B cell differentiation so that mCD43 was now expressed on peripheral B cells. Despite having increased B cells, localization of lymphocytes in the TG spleens appeared normal by immunocytochemistry with anti-CD4, anti-CD8, and anti-B220 mAbs. However, the numbers of splenic germinal centers and the resting sera Ig levels were decreased in the TG mice compared with littermate controls. TG mice had decreased humoral responses to the T-dependent Ags keyhole limpet hemocyanin and OVA, as well as reduced Ag-specific B cell numbers. In contrast, in vitro LPS stimulation of purified TG or control B cells resulted in similar proliferation and IgM responses. Thus, the alteration of B cell mCD43 expression that resulted in profound immunodeficiency in vivo was not due to absolute defects in B cell development or Ab production. However, TG B cells had a decreased ability to homotypically aggregate and to present Ag to the T cell hybridoma B3Z. These data suggest that the immunodeficiency seen in vivo is due to the anti-adhesive forces of mCD43 preventing normal T-B cell interaction. This likely reflects a general property of mucins in regulating cell interactions.
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PMID:Disregulated expression of CD43 (leukosialin, sialophorin) in the B cell lineage leads to immunodeficiency. 894 91

We report two cases of marginal zone B-cell lymphoma in two patients 6 and 18 years of age, respectively (cases 1 and 2) who had no clinical evidence of immunodeficiency or risk factors for human immunodeficiency virus (HIV) infection. Histologic analysis in both cases revealed diffuse nodal effacement by a monotonous population of atypical lymphoid cells with abundant pale cytoplasm and round to oval nuclei, with very infrequent mitotic activity. The neoplastic cells in both cases were of B-cell lineage (CD20 and CD79a positive), with CD43 coexpression. One case showed monoclonal light chain expression, and polymerase chain reaction analysis demonstrated clonal rearrangements of the immunoglobulin heavy chain gene in both cases. Abnormal cytogenetic findings were detected in case 2, in which metaphase spreads revealed trisomy 13 (karyotype 47, XY, +13). Although trisomy 13 has been described in association with acute nonlymphocytic leukemias and myelodysplastic syndromes, this case represents the first documented association of trisomy 13 with marginal zone B-cell lymphoma. Interphase cytogenetics analysis for trisomy 3, reported to be associated with mucosa-associated lymphoid tissue (MALT) lymphomas, was negative in both cases. Although low-grade lymphomas of the MALT type have been reported in HIV-positive patients, the two cases reported here are unique in that they occurred in young patients without HIV infection or any other evidence of immunodeficiency.
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PMID:Marginal zone B-cell lymphoma with monocytoid B-cell lymphocytes in pediatric patients without immunodeficiency. A report of two cases. 898 Mar 74

An increased prevalence of intermediate- and high-grade B-cell non-Hodgkin's lymphoma (NHL) is a major manifestation of the disease spectrum associated with human immunodeficiency virus (HIV) infection. Rarely, lymphoproliferations are of T-cell, null cell, or mixed-lineage phenotypes. We describe an unusual B-cell NHL that presented as a left alar ulcer in a man with acquired immunodeficiency syndrome (AIDS) and rectal carcinoma. Biopsy of the lesion and a draining cervical lymph node showed atypical dermal lymphoid infiltration with effacement of nodal architecture and involvement of adjacent skeletal muscle by a diffuse infiltrate of large and small lymphocytes. On paraffin section immunochemistry, the large lymphoid cells expressed CD45 and CD45RO, but not CD43 or CD20. The small background cells were positive for CD3, CD43, and CD45RO. These overall results were consistent with a diagnosis of a T-cell process. Gene rearrangement studies, however, demonstrated a clonal B-cell population indicative of B-cell NHL. The clinical course was marked by rapid shrinkage of tumor with chemotherapy followed by profound wasting and death. Anomalous coexpression or lack of expression of T- and B-cell markers may be seen in AIDS-related NHL. Reliance on paraffin section immunohistology may provide misleading information, and caution is recommended in assigning a specific lineage to such lymphoproliferations without additional immunologic or genotypic analyses. Whether our case represents a distinct clinicopathologic entity or is simply a peculiar manifestation of HIV-related B-cell NHL remains uncertain.
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PMID:AIDS-associated B-cell non-Hodgkin's lymphoma masquerading as a cutaneous T-cell neoplasm: an aberrant immunophenotype requiring comprehensive analysis for lineage resolution. 905 57

Complementary DNA encoding a human Gal(beta1-3)GalNAc alpha2,3-sialyltransferase type II (hST3Gal II) was cloned from a CEM T-cell cDNA library using a 23-base oligonucleotide probe. The sequence of this probe was established on the basis of a slightly divergent sialylmotif L that was obtained by polymerase chain reaction with degenerate oligonucleotide primers based on the conserved sialylmotif L of mammalian Gal(beta1-3)GalNAc alpha2,3-sialyltransferases. It was thus confirmed that a short oligonucleotide probe may be sensitive and highly specific. The nucleotide and amino acid sequences of hST3Gal II show, respectively, 56.3% and 49.3% similarity to hST3Gal I [Kitagawa, H. & Paulson, J. C. (1994) J. Biol. Chem. 269, 17872-17878] and 88.1% and 93.7% similarity to murine ST3Gal II [Lee, Y. C., Kojima, N., Wada, E., Kurosawa, N., Nakaoka, T., Hamamoto, T. & Tsuji, S. (1994) J. Biol. Chem. 269, 10028-10033]. hST3Gal II mRNA was highly expressed in heart, liver, skeletal muscle and various lymphoid tissues but not in brain and kidney. A soluble form of hST3Gal II expressed in COS-7 cells was tested in vitro for substrate specificity and kinetic properties. Asialofetuin and asialo-bovine submaxillary mucin appeared better substrates for hST3Gal II than for its murine counterpart as previously reported [Kojima, N., Lee, Y.-C., Hamamoto, T., Kurosawa, N. & Tsuji, S. (1994) Biochemistry 33, 5772-5776]. In previous studies, we have shown hyposialylation of O-glycans attached to two major lymphocyte CD43 and CD45 cell surface molecules in human-immunodeficiency-virus-1(HIV-1)-infected T-cell lines. Since comparable levels of hST3Gal I and hST3Gal II mRNA and enzymatic activity were observed in parental and HIV-1-infected CEM T-cell lysates, the sialylation defect associated with HIV infection of this cell line is probably due to a mechanism different from a simple altered catalytic activity of these sialyltransferases.
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PMID:Cloning and expression of cDNA for a human Gal(beta1-3)GalNAc alpha2,3-sialyltransferase from the CEM T-cell line. 926 97


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