Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemophagocytic lymphohistiocytosis, terminology that designates a syndrome that may be familial or sporadic, with or without an associated viral infection, is presented as the prototype of a hemophagocytic syndrome, a condition in which there is uncontrolled activation of the cellular immune system. Diagnostic criteria include idiopathic fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, and the presence of hemophagocytosis. The surgical and autopsy pathology features infiltrates composed of lymphocytes and ordinary, but activated, histiocytes and hemophagocytosis. The chronic hepatitis-like hepatic lesion is noted to be characteristic, if not unique, in this age group and setting. Current concepts of pathophysiology focus on the role of cytokines, particularly interleukin (IL)-1, IL-2, soluble IL-2 receptor, plasminogen activator, and prostaglandins. The clinicopathologic features of the syndrome can be accounted for by the uncontrolled and unopposed production and release of these mediators. Nosology places hemophagocytic lymphohistiocytosis in the position of the most important of the "benign" histiocytosis syndromes that involve ordinary histiocytes of the mononuclear phagocytic system in contrast to Langerhans cell histiocytosis (histiocytosis X) in which pathological dendritic histiocytes are operative. Features that distinguish hemophagocytic lymphohistiocytosis from other disorders, such as malignant histiocytosis, X-linked lymphoproliferative disorder, congenital immunodeficiency states, the accelerated phase of Chediak-Higashi syndrome, and cytophagic histiocytic panniculitis, which may be associated with a hemophagocytic syndrome, are presented.
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PMID:Hemophagocytic lymphohistiocytosis: a hemophagocytic syndrome. 156 89

A novel X-linked combined immunodeficiency disease was found in five living males in an extended family in the United States. The age of the affected males ranged from 2.5 to 34 yr. The most prominent clinical abnormalities were a paucity of lymphoid tissue; recurrent sinusitis, otitis media, bronchitis, and pneumonia; severe varicella; and chronic papillomavirus infections. The principal immunologic features of the disorder were normal concentrations of serum immunoglobulins but restricted formation of IgG antibodies to immunogens; normal numbers of B cells and NK cells but decreased numbers of CD4+ and CD8+ T lymphocytes, particularly the CD45RA+ subpopulations; diminished proliferative responses of blood T cells to allogeneic cells, mitogens and antigens; and decreased production of IL-2 by mitogen stimulated blood lymphocytes. Thus, affected males in this family carry an abnormal gene on their X chromosome that results in a combined immunodeficiency that is distinct from previously reported disorders.
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PMID:A novel X-linked combined immunodeficiency disease. 224 35

The ability of human recombinant IL-2 to induce NDP-kinase in mouse NK cells has been studied. A significant increase in the amount of NDP-kinase was observed when the cells were exposed to IL-2 (100 units/ml) for 3 h at 37 degrees C. The enzyme inducting ability of human recombinant IL-2 was similar to that of native mouse IL-2 in the cells. The enzymatic characteristics [chemical requirements for the phosphoenzyme formation and molecular size of two distinct subunits (18,000 and 20,000 daltons)] of NDP-kinase from IL-2 treated cells were similar to those of the enzymes from EAT cells. The enzyme's biological role in the initiation of cell proliferation by IL-2 has been discussed.
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PMID:Nucleosidediphosphate-kinase induction by human recombinant IL-2 in mouse NK cells. 298 83

Allogeneic bone marrow transplantation (BMT) was applied in 1968 to treat severe combined immunodeficiency disease (SCID). Almost simultaneously, marrow from an MHC-matched donor corrected the immunological deficiency of a patient with Wiscott-Aldrich Syndrome (WAS). In the first successful treatment of X-linked SCID the match was imperfect and, although SCID was cured, a graft vs. host reaction caused pancytopenia. A second BMT from the same donor successfully treated a complicating aplastic anemia. Subsequently, it has been possible to cure most patients with SCID who are in reasonably good condition at the time of BMT without other manipulation if a matched sibling donor is available. Successes are reported from Holland, France, Italy, England, Scandinavia, Japan, Germany, and from many centers in the United States. Similarly, BMT is used to correct SCID due to adenosine deaminase (ADA) deficiency or nucleoside phosphorylase (NP) deficiency, which underlie two forms of SCID. Bone marrow transplantation using HLA-matched sibling donors can now treat, successfully, at least eight genetically separable forms of SCID. Highly lethal defects of phagocytic function (including LFA-1, MO-1, CR-3 deficiencies, IL-2 and IL-1 receptor deficiencies), defects of killing after phagocytosis (as in chronic granulomatous disease, WAS, and Kostmann's Syndrome), and certain inborn errors of metabolism can be cured by BMT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone marrow transplantation for immunodeficiency diseases. 330 7

The mAb L10 was used to determine the distribution and the function of sialophorin, the heavily glycosylated surface molecule that is deficient/defective in lymphocytes of patients with the X-linked immunodeficiency Wiskott-Aldrich syndrome. Dual-parameter FACS analysis indicated that sialophorin is expressed on CD4+ and CD8+ lymphocytes, on a subpopulation of peripheral blood B lymphocytes, on all thymocytes, and on a subpopulation of bone marrow cells. Functional studies demonstrated that L10 mAb stimulates the proliferation of peripheral blood T lymphocytes as measured by stimulation of [3H]thymidine incorporation. The time course and magnitude of increased [3H]thymidine incorporation by T lymphocytes in response to L10 mAb paralleled that induced by anti-CD3 mAb. Effective stimulation was dependent on the presence of monocytes and the Fc portion of L10 mAb. Stimulation of lymphocytes by L10, like stimulation by anti-CD3 mAb, involves increased expression of 4F2, HLA-DR, and IL-2-R. These observations suggest that sialophorin functions in T cell activation.
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PMID:Sialophorin, a surface sialoglycoprotein defective in the Wiskott-Aldrich syndrome, is involved in human T lymphocyte proliferation. 357 1

The interaction between the CD40 ligand (gp39), expressed by activated T cells, and CD40, constitutively expressed by B cells, is critical for an effective antibody response to T cell dependent antigens. Patients with X-linked hyper IgM (HIM) syndrome fail to express a functional CD40 ligand due to a mutation within the gene for gp39. As a direct consequence, HIM patients, when immunized with T dependent antigens, produce only small amounts of IgM antibody without the development of immunologic memory, amplification and switch from IgM to IgG. Mutations affecting the gene for the HIM syndrome are localized throughout the coding region of gp39 and consist predominantly of point mutations. The resulting amino acid substitutions interfere directly with the receptor binding site or lead to stop codons or deletions secondary to splice site mutations. Expression of gp39 by activated T cells from patients with common variable immunodeficiency (CVI) is low in approximately half of the patients and is associated with depressed expression of IL-2. These findings suggest that inefficient signaling via CD40 may be responsible in part for failure of B cell differentiation in CVI.
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PMID:The role of CD40L (gp39)/CD40 in T/B cell interaction and primary immunodeficiency. 753 62

CD38 is a 42 kDa membrane-associated ectoenzyme expressed by a large proportion of human and mouse lymphocytes. Agonistic antibodies to CD38 induce a strong proliferative response in lymphocytes additionally co-stimulated with other growth co-factors such as IL-4, IL-2 plus accessory cells or sub-mitogenic doses of endotoxin. We show here that B lymphocytes from unstimulated X-linked immunodeficient (xid) mice are unresponsive to CD38 stimulation, both in terms of proliferative response and surface antigen modulation. This CD38 unresponsiveness is evident in the presence of excess quantities of, and normal responses to, the accessory growth co-stimulants required for this response. CD38 molecules expressed on xid B cells are normal in terms of expression levels, size and enzymatic activity, suggesting that CD38 unresponsiveness reflects a down-stream signaling defect. In light of the recent proposal that the xid gene encodes a tyrosine kinase called Bruton's tyrosine kinase (btk), these data suggest that btk is either an integral component or an indirect regulator of the CD38-induced signal transduction pathway.
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PMID:CD38 unresponsiveness of xid B cells implicates Bruton's tyrosine kinase (btk) as a regular of CD38 induced signal transduction. 773 14

The protein-tyrosine kinase gene Itk is expressed preferentially in T lymphoid cells of the mouse and is induced by IL-2. A related gene, Btk, is expressed in the murine B lymphoid and myeloid lineages. Because mutations in Btk and the corresponding human gene are associated with X-linked immunodeficiency syndromes, it was of interest to map Itk and its human counterpart. By Southern blot analysis of DNA from the progeny of two multilocus crosses, murine Itk was mapped to Chromosome 11. By fluorescence in situ hybridization, human ITK was mapped to 5q32-q33. Murine Itk and its human homologue lie within regions of conserved synteny that include several growth factor and growth factor receptor genes. This region in humans is frequently deleted in the myelodysplastic syndrome, suggesting possible involvement of ITK in this disorder.
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PMID:Mapping of the gene for the tyrosine kinase Itk to a region of conserved synteny between mouse chromosome 11 and human chromosome 5q. 782 87

The IL2RG gene encoding the gamma chain of the lymphocyte receptor for IL-2 lies in human Xq13.1 and is mutated in males with X-linked severe combined immunodeficiency (SCID). In a large Canadian pedigree genetic linkage studies demonstrated that the proband's grandmother was the source of an X-linked SCID mutation. However, her T cells did not show the expected skewed X chromosome inactivation pattern of female carriers of SCID, despite her having one affected son and two carrier daughters with skewed X inactivation. Single strand conformation polymorphism analysis of IL2RG in the affected proband was abnormal in exon 5; sequencing revealed a nine nucleotide in-frame duplication insertion. The three duplicated amino acids included the first tryptophan of the "WSXWS" motif found in all members of the cytokine receptor gene superfamily. Mutation detection in the pedigree confirmed that the founder grandmother's somatic cells had only normal IL2RG, and further showed that the SCID-associated X chromosome haplotype was inherited by three daughters, one with a wild type IL2RG gene and two others with the insertional mutation. Female germ line mosaicism is unusual, but its presence in this X-linked SCID family emphasizes the limitations of genetic diagnosis by linkage as compared with direct mutation analysis.
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PMID:Female germ line mosaicism as the origin of a unique IL-2 receptor gamma-chain mutation causing X-linked severe combined immunodeficiency. 786 Jul 24

The molecular basis for three well-defined X-linked diseases has recently been identified. In X-linked agammaglobulinemia, the gene encoding a novel cytoplasmic tyrosine kinase (btk) expressed by B cells is defective. This B-cell-specific kinase belongs to a new subfamily of tyrosine kinases. The molecular defect in X-linked hyper IgM affects the gene encoding the CD40 ligand (CD40L, gp39) on T cells. This protein binds to its natural receptor, CD40, expressed constitutively by B cells. The ligand-receptor interaction initiates B-cell proliferation and isotype switching. The molecular defect in X-linked severe combined immunodeficiency disease has been assigned to the gene encoding the gamma chain of the interleukin-2 receptor (IL-2R gamma), which is constitutively expressed by T cells and is involved in the formation of high and intermediate affinity IL-2R complexes. IL-2R-gamma is responsible for the failure of X-linked severe combined immunodeficiency disease T and B lymphocytes to respond to IL-2-dependent signals.
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PMID:Advances in X-linked immunodeficiency diseases. 790 59


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