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)

The molecular bases of the X-linked immunodeficiency diseases remain largely undetermined. Two of the genes involved in these diseases have been isolated, namely the genes for X-linked chronic granulomatous disease and properdin deficiency, and substantial progress has now been made in identifying the genes which are defective in the other five diseases, Wiskott-Aldrich syndrome, X-linked severe combined immunodeficiency, X-linked agammaglobulinaemia, X-linked hyper-IgM and X-linked lymphoproliferative syndrome. We review here the nature of the diseases, progress made in identifying and isolating the genes involved and the prospects for improved prenatal detection, carrier status determination and treatment of these life-threatening conditions.
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PMID:The molecular basis of X-linked immunodeficiency disease. 152 25

We studied visual impairment caused by benign lymphoid infiltration of the vitreous bilaterally, as a complication of a primary immunodeficiency, X-linked immunodeficiency with increased IgM in an 8-year-old boy. Immunophenotyping of a vitreous aspirate showed a mixed cell population, including lymphocytes (T helper, suppressor-cytotoxic T cells, and B cells) and macrophages. Cultures of the vitreous were negative for bacterial or fungal pathogens. The vitreous infiltrates have been resistant to treatment with corticosteroids and cytotoxic agents.
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PMID:Cellular infiltration of the vitreous in a patient with X-linked immunodeficiency with increased IgM. 155 Jan 86

Immunodeficiency with hyper-IgM (HIM) is a rare disorder characterized by recurrent infections associated with low IgG and IgA, and normal to increased IgM serum levels. Both primary and secondary forms of HIM syndrome have been reported. Among primary HIM syndrome, evidence for genetic heterogeneity is provided by the occurrence of the disease as X-linked, autosomal recessive, or autosomal dominant trait. The most common clinical manifestations include upper and lower respiratory tract infections, otitis, diarrhoea, oral ulcers, lymphoid hyperplasia, and autoimmunity. Recurrent neutropaenia is a frequent finding. Immunological abnormalities consist of lack of IgG and IgA secretion, and failure to respond to vaccination. Lymph nodes show absence of germinal centres. Few patients with a concurrent T-cell defect, and clinical expression of combined immune deficiency, have been reported. The gene responsible for the X-linked HIM syndrome (HIGM1) has been tentatively assigned to Xq24-27. However, carrier detection and prenatal diagnosis are not yet possible. Pathogenetic hypotheses include failure of B-cell differentiation, and defective regulation of immunoglobulin isotype switching due to abnormal T-cell-mediated signals. Treatment is mainly based upon regular administration of intravenous immunoglobulins. Steroids may be useful in the treatment of neutropaenia and of severe autoimmune manifestations.
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PMID:Immunodeficiency with hyper-IgM (HIM). 155 97

The Wiskott-Aldrich syndrome (WAS) is an inherited disease involving defects of platelets (small size, severe thrombocytopenia due to accelerated destruction) and T lymphocytes (progressive immunodeficiency, lymphopenia). The best-characterized molecular defect is the deficiency and, in some cases, abnormal forms of the T-lymphocyte surface mucin molecule CD43; deficiency of the platelet surface mucin GPIb was observed previously in two of four patients. Neither of these defects is primary, since CD43 and GPIb are encoded by autosomal genes and the disease is X-linked. This study uses cellular biological approaches to explore the possibility that destruction of structurally defective WAS platelets, mimicked experimentally by sonication of normal platelets, plays a role by releasing protease and generating other cellular defects. We show that a protease of normal platelets, identified as Ca(2+)-dependent neutral protease (calpain), which is known to cleave platelet GPIb, also specifically cleaves CD43 on the surface of neighboring desialylated T lymphocytes. The identification of the CD43 cleaving protease was based on its requirement for Ca2+ and inhibition by leupeptin, but not by diisopropylfluorophosphate (DFP). The approximate site of CD43 cleavage was identified by the use of a rabbit antibody. Sensitivity of GPIb to calpain is shown to be sialylation-independent and that of CD43 to be sialylation-dependent, and these findings are explained in terms of molecular structures. These and previous findings are incorporated into a putative mechanism, which explains most of the defects in the WAS. The mechanism suggests that the primary defective molecule in the WAS is unlikely to be a surface glycoprotein, but rather a cytoplasmic molecule with a function in cytoskeletal interactions and/or calcium ion regulation and calpain activation.
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PMID:Effect of platelet calpain on normal T-lymphocyte CD43: hypothesis of events in the Wiskott-Aldrich syndrome. 155 70

We previously reported an X-linked combined immunodeficiency disease (CID) characterized by immune deficiencies and complicating infections that were more moderate than those found in severe CID (SCID). Since other unstudied males in the family died in infancy, we questioned whether this T cell defect was more profound in early life. Subsequently, the development of blood T cells in an affected newborn male was examined. T cells were virtually undetectable at 48 hr. Over the next several months, CD4+ T cells (principally CD45RO+) rose to levels similar to those found in older affected males, but CD8+ T cells developed more slowly and never attained levels found in other affected males. Thus, this disease in early life mimics SCID and may pose a higher risk of fatal infections to affected individuals during that period. Finally, we speculate that the genetic defect may disrupt intrathymic development or selection of T cells.
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PMID:Postnatal development of T lymphocytes in a novel X-linked immunodeficiency disease. 160 54

Although X-linked lymphoproliferative disease (XLP) is rare (1-2 males per 1 x 10(6)), it serves as a model for discerning diverse diseases caused by Epstein-Barr virus (EBV) ranging from agammaglobulinemia to fatal infectious mononucleosis following infection with the virus. The study of patients with XLP has also paved the way to understanding how EBV induce diseases in children with primary immunodeficiency diseases, organ transplant recipients, and those with acquired immunodeficiency syndrome. This review is dedicated to the memory of Gordon Vawter, M.D., who generously provided insights into the causes of pathogenesis of immune deficiency and lymphoproliferative disorders.
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PMID:The X-linked lymphoproliferative disease: from autopsy toward cloning the gene 1975-1990. 166 Jun 1

Preferential use of particular VH gene families in the response to specific antigens has been demonstrated in several systems. The lack of responses to certain types of antigens, therefore, could be the result of deletion of or failure to express some VH genes. Because CBA/N mice, which carry the X-linked immunodeficiency (xid) gene defect, have been shown to be unresponsive to thymus-independent polysaccharide antigens, it was of interest to examine if this unresponsiveness could be accounted for by abnormal expression of particular VH gene families. Using in situ hybridization on B cell colonies, we determined the expression of nine VH gene families in CBA/CaHN females (genotypically normal), CBA/N males (xid) and females (xid), and (CBA/N x CBA/CaHN)F1 males (xid) and females (phenotypically normal). Our results indicate that VH gene family expression, including the S107 family, in CBA/N males and F1 males, is similar to that of CBA/CaHN and F1 females with predominant expression of J558, the largest gene family, in all individuals. Interestingly, CBA/N female mice, which carry two defective X chromosomes, as a group expressed significantly reduced levels of the J558 gene family, and as individuals showed variation in which family was predominantly expressed. We conclude that the unresponsiveness of mice with the xid defect to polysaccharide antigens can not attributed to a failure to express the nine VH gene families that we examined. Our findings do not support previous studies (Primi, D., and P.-A. Cazenave 1986. J. Exp. Med. 165:357), which found an absence of expression of the S107 family in xid mice.
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PMID:VH gene family expression in mice with the xid defect. 171 66

Recent reports of persistent engraftment of human lymphocytes and myeloid cells in hereditary immunodeficient severe combined immunodeficient mice (SCID) and beige athymic nude X-linked immunodeficiency (Bg/Nu/XID) mice have raised the question of why attempts to graft human cells into artificially immunosuppressed normal mice have failed so far. In the present study we provide evidence that this difference is due to the absence of natural antibodies in the mutant mice. We demonstrate that human PBL can be grafted in normal mice immunosuppressed by heavy doses of total body irradiation, provided the transplant is performed when the recipients lack natural antibodies in their serum, e.g. as in newborn normal mice, in mice treated with anti-mouse IgM antibody from birth, and in 3-week-old B cell-deficient CBA/N mice. In all cases, large numbers of human PBL were required. Under these conditions an acute and fatal graft vs. host disease (GVHD) developed in the recipients, regardless of whether these were artificially immunosuppressed or hereditary immunodeficient. The clinical manifestations and the histopathology of this xenogeneic acute GVHD are quite different from those of allogeneic GVHD. The former is primarily confined to the hematolymphoid tissues and locations close to accumulations of proliferating lymphoblasts, such as the peritoneal cavity in case of i.p. transplantation. The discordant xenogeneic GVHD is induced by human T lymphocytes and can be abrogated by treatment with anti-human T cell serum.
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PMID:Acute human vs. mouse graft vs. host disease in normal and immunodeficient mice. 173 Feb 49

The observation that approximately half of the B cells in the murine intestinal lamina propria are derived from peritoneal CD5 B-cell precursors raises the question of their contribution to mucosal protection. Using mice with X-linked immunodeficiency which are deficient in CD5+ B cells, we showed that they mount little serum and virtually no intestinal immunoglobulin M (IgM), IgG, and IgA antibody responses following oral inoculation with live Salmonella typhimurium. Nonresponsive Xid mice were reconstituted with responsive CBA/Ca donor cell preparations which were constitutively enriched or depleted of CD5 B-cell precursors. Reconstitution of irradiated Xid mice with CD5 B-cell-deficient bone marrow from CBA/Ca donors marginally improved IgM responses in the intestinal mucosa but had no effect on IgG or IgA in response to oral immunization with live S. typhimurium. Whenever Xid mice were reconstituted with donor cells from the peritoneal cavity, which are enriched for CD5 B-cell precursors, strong IgA and in some cases IgG responses in the intestinal mucosa were stimulated in response to oral immunization. When mucosal and serum antibody responses were compared, the peritoneal donor cells again reinstated maximal serum antibody responses to S. typhimurium. Serum and mucosal responses to the bacterial hapten phosphorylcholine could be induced in Xid mice after immunization with S. typhimurium or hapten-carrier conjugates but only following reconstitution with donor cells containing CD5 B-cell precursors. These observations suggest that different lymphoid compartments are enriched for regulatory or effector cells which vary in their contributions to the mucosal antibody response against epitopes on S. typhimurium.
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PMID:Enhancement of mucosal antibody responses to Salmonella typhimurium and the microbial hapten phosphorylcholine in mice with X-linked immunodeficiency by B-cell precursors from the peritoneal cavity. 173 Apr 82

The Wiskott-Aldrich Syndrome (WAS) is a rare X-linked immunohematological disorder characterized by eczema, profound thrombocytopenia, and progressive immunodeficiency. Severe hemorrhage, overwhelming sepsis, or lymphoreticular malignancy usually cause death in childhood. Recently, bone marrow transplantation (BMT) has been curative in some well-established cases, but there is no general agreement about the place of BMT in infants with WAS before the development of significant immunological abnormalities. We describe the successful use of early histocompatible BMT in a 10-month-old infant in whom WAS was diagnosed on the basis of eczema, thrombocytopenia, small platelets, and raised serum immunoglobulin A (Ig) and IgE, but before the development of immunodeficiency as evidenced clinically by recurrent infections, or immunologically by low serum IgM or consistently abnormal lymphocyte responses to mitogens. After an unstable period for several weeks posttransplantation when he developed marked hepatomegaly and severe interstitial pneumonitis, he made a good recovery. His eczema and thrombocytopenia resolved and he has shown no clinical or laboratory evidence of immunodeficiency. It is now over 2 years since his BMT. Because of the poor prognosis of WAS, where a histocompatible donor is available, BMT at the earliest opportunity, despite the inherent risks of such a procedure, may be the best option for an infant with WAS.
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PMID:Early bone marrow transplantation in an infant with Wiskott-Aldrich syndrome. 179 57


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