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

X-linked agammglobulinemia (XLA) is a ptototypical humoral immunodeficiency caused by mutations in the gene coding for Bruton tyrosine kinase (BTK). The genetic defect in XLA impairs early B cell development resulting in marked reduction of mature B cells in the blood. Studies from different countries have demonstrated that approximately 90% of males with presumed XLA bear mutations in BTK. In this study, we report for the first time the occurrence of BTK mutations in Turkey. We performed mutational analysis of the BTK gene in 16 Turkish male patients from 13 separate families with presumed XLA based on abnormally low peripheral blood B-cell numbers (lt; 1%), hypogammaglobulinemia, and recurrent bacterial infections. We found that in nine of the 13 families (69%) a Btk mutation caused XLA. Two of the mutations were previously described, but seven novel mutations were identified: two missense (Y39C, G584R), one nonsense (Q343X), and 4 deletions (1800-1821del, 1843-1847del, 1288-1292del, 291del) resulting in frameshift and premature stop codon. By contrast, no mutations in the BTK gene were identified in the other 4 families. A consanguinity in three of these families raises the possibility that mutations in other autosomal genes which affect early B cell development may contribute to their phenotype resembling XLA.
 ...
PMID:Bruton tyrosine kinase gene mutations in Turkish patients with presumed X-linked agammaglobulinemia. 1166 22

Mouth ulcers are commonly caused by infection but may be due to neutropenia. The most common form of hyper-IgM syndrome is of X-linked inheritance and caused by CD40 ligand gene mutations. Consider hyper-IgM syndrome in a male child with recurrent bacterial or opportunistic infections, neutropenia, hypogammaglobulinaemia (IgG and IgA) and normal T- and B-cell counts. In X-linked hyper-IgM syndrome: - the serum IgM concentration is normal in about 50% of cases. - transient or persistent neutropenia occurs in 70% of cases. First-line therapeutic options for hyper-IgM syndrome include regular intravenous immunoglobulin and prophylactic trimethoprimsulphamethoxazole.
 ...
PMID:Fevers and mouth ulcers. 1188 19

X-linked, or Bruton's, agammaglobulinemia (XLA) was described in 1952 as the congenital inability to form antibodies. Patients were typically infants or young children with recurrent, severe bacterial infections. Other, milder cases of hypogammaglobulinemia were considered "acquired," and often presented later in life. Since the discovery of the defective gene in XLA in 1993, it has been shown that a significant number of male patients with sporadic or acquired hypogammaglobulinemia actually have XLA. We present here a case of atypical XLA and discuss similar cases in the literature. We conclude that any male with hypogammaglobulinemia, regardless of age of presentation, might have XLA. Males with low B-cell numbers are particularly likely to have XLA and should have Bruton's tyrosine kinase levels assessed.
 ...
PMID:The clinical spectrum of Bruton's agammaglobulinemia. 1189 85

Primary hypogammaglobulinemia (Bruton's disease) is a rare X-linked infantile immunodeficiency syndrome due to a B-cell defect. The patients suffer from acute and recurrent bacterial infections with chronic rhinosinusitis and chronic lung disorders. Immunoglobulin replacement therapy and antibiotics do not suffice in some cases, making sinus surgery to advance the drainage necessary. A 25-year-old man with hypogammaglobulinemia was treated with functional endoscopic sinus surgery and mucotomy of the turbinates. Tissue samples of the inferior turbinates were taken for histological and electron-microscopic examination. Immuno-electron-microscopic methods were carried out with antibodies against substance P and calcitonin gene-related peptide (CGRP). Morphological investigations to better understand pathophysiological changes in hypogammaglobulinemia are rare. Pathological changes in the glands and venous vessels could be demonstrated. A rich neural supply and participation of neuropeptides such as substance P and CGRP could play a role in the unspecific defense via neurogenetic inflammation in these cases.
 ...
PMID:[Chronic rhinosinusitis in hypogammaglobulinemia. A morphological study]. 1221 74

X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency characterized by extreme vulnerability to Epstein-Barr virus (EBV) infection, resulting in fatal infectious mononucleosis, dysgammaglobulinemia and malignant lymphoma. Recently, mutations in the SH2D1A gene, which encodes SLAM-associated protein (SAP), have been found to cause XLP. Although the molecular events behind XLP are largely unknown, there is evidence that affected males exhibited some immunohematological abnormalities, such as hypogammaglobulinemia or lymphoma, even prior to EBV infection. Because of the poor prognosis in XLP, an early diagnosis to patients and families is clinically of great importance. A glutathione-S-transferase-SAP fusion protein was used to immunize rats and generate mAb against human SAP to investigate its pathogenic role in XLP and develop a flow cytometric assay for detection of XLP. By flow cytometric and Western immunoblot analyses using an established anti-SAP mAb, termed KST-3, we determined that SAP was expressed intensely in thymocytes, but at lower levels in peripheral T cells and NK cells. In contrast, expression of SAP was negligible in B cells, monocytes or granulocytes. We found that SAP expression in T cells increased upon in vivo as well as in vitro activation. In two XLP survivors with SH2D1A mutations, a flow cytometric evaluation of activated T cells using KST-3 could demonstrate SAP deficiency as a diagnostic indicator of XLP. Through this approach, we identified three novel XLP families with SH2D1A mutations in Japan. A flow cytometric assessment of SAP expressed in activated T cells would lead to easy detection of XLP patients.
 ...
PMID:Activation-dependent T cell expression of the X-linked lymphoproliferative disease gene product SLAM-associated protein and its assessment for patient detection. 1235 86

Epstein-Barr virus (EBV) is implicated in a variety of human diseases, some of which have fatal outcomes. Some EBV related diseases are considered to be candidates for the treatment of hematopoietic stem cell transplantation (HSCT). X-linked lymphoproliferative (XLP) syndrome is one of the representative diseases in which more than half of affected males die of infectious mononucleosis (IM) within a few weeks of primary infection, whereas the minority who survive have an increased risk of acquired hypogammaglobulinemia and lymphoma. Patients with XLP usually die by the age 40. Similarly, the majority of patients with chronic active EBV infection develop hemophagocytic syndrome, organ failure, opportunistic infection, and/or lymphoma and die within 5-10 years from onset. Recently, HSCT has provided successful outcomes in these patients. In this review, progress in the new therapeutic strategy is summarized, focusing on EBV-associated T/NK-cell lymphoproliferative disease (LPD), which is one of the heterogeneous EBV-associated disorder.
 ...
PMID:Allogeneic hematopoietic stem cell transplantation for Epstein-Barr virus-associated T/NK-cell lymphoproliferative disease. 1246 65

Mutations in SH2D1A, a gene that codifies for the regulatory protein SAP, result in uncontrolled activation of the SLAM (signaling lymphocyte-activation molecule) pathway. This X-linked immunodeficiency becomes evident when the patients are infected with Epstein Barr virus (EBV) and develop a fulminant form of infectious mononucleosis leading to a lymphoproliferative syndrome that is often fatal (X-linked lymphoproliferative syndrome, XLP). In those who survive, hypogammaglobulinemia and oncohematologic diseases are frequently observed. In this revision, the immuno-regulatory mechanisms involved in XLP immunopathology and the role of different effector cells (CD8 T lymphocytes, NK cells) are discussed.
 ...
PMID:[X-linked lymphoproliferative syndrome, EBV virus infection and defects in cytotoxicity lymphocyte regulation]. 1267 66

Detailed longitudinal studies of patients with X-linked lymphoproliferative disease (XLP) may increase our understanding of the immunologic defects that contribute to the development of lymphoma and hypogammaglobulinemia in XLP. We describe progressive changes observed in immunoglobulin concentrations, lymphocyte subsets, and Epstein-Barr virus (EBV) loads occurring in a 2-year period in a newly infected, but otherwise healthy, carrier (patient 9). We compare these findings with those observed in the patient's brother, who had hypogammaglobulinemia and XLP (patient 4). Immunoglobulin G (IgG), IgM, and IgA concentrations increased in patient 9 during acute EBV infection, but thereafter they decreased steadily to concentrations consistent with hypogammaglobulinemia, reaching a plateau 5 months after infection. In both patients, CD19+ B-lymphocyte rates remained lower than 3%, with a contraction of the B-cell memory compartment (CD27+ CD19+/CD19+) to 20% (normal range, 32%-56%). T-lymphocyte subpopulations showed a reduction in CD4+ T-cell counts and a permanent CD8+ T-cell expansion. Interestingly, CXCR3 memory TH1 cells were expanded and CCR4+ TH2 lymphocytes were reduced, suggesting that abnormal skewing of memory T-cell subsets might contribute to reduced antibody synthesis. Despite an expanded number of CD3+CD8+ lymphocytes, increased EBV loads occurred in both patients without overt clinical symptoms of mononucleosis, lymphoproliferative disease, or lymphoma.
 ...
PMID:Loss of circulating CD27+ memory B cells and CCR4+ T cells occurring in association with elevated EBV loads in XLP patients surviving primary EBV infection. 1460 60

Hypogammaglobulinemia is a common symptom in different immunodeficiencies. It is, however, not usually associated with Epstein-Barr virus (EBV) infections. The X-linked lymphoproliferative disease (XLP) on the other hand shows immunological changes in response to the EBV. Here we report three previously healthy boys, all of which developed persistent hypogammaglobulinemia following severe acute infectious mononucleosis. All three patients revealed T-cell abnormalities including inverted CD4/CD8 and increased CD8(+) T-cell numbers. The number of IFN-gamma-producing T cells were markedly increased in the two patients studied so far. In addition, patient 2 showed mainly T cells, instead of B cells, to be infected with the EBV. Apart from an uncle of patient 3, who died of malignant lymphoma, family history was unremarkable in all cases. All three patients exhibited mutations in the SH2D1A gene, establishing the diagnosis of XLP. Protein expression was found on immunoblot analysis in one patient with a missense mutation. Development of persistent hypogammaglobulinemia after severe primary EBV infection seems to be a specific diagnostic sign for XLP even in males with unremarkable family history.
 ...
PMID:Persistent hypogammaglobulinemia following mononucleosis in boys is highly suggestive of X-linked lymphoproliferative disease--report of three cases. 1535 10

We retrospectively reviewed the clinical and immunological features as well as the outcome of children with a diagnosis of primary hypogammaglobulinemia, who were treated at the National Taiwan University Hospital between 1984 and 2001. A total of 33 patients were enrolled: seventeen patients with common variable immunodeficiency (CVID), six patients with selective immunoglobulin deficiencies (one subclass IgA and five IgG), four patients with severe combined immunodeficiency (SCID), three patients with transient hypogammaglobulinemia of infancy (THI) and three patients with X-linked (Bruton) agammaglobulinemia (XLA). In addition to recurrent sinopulmonary infections and prolonged fever, allergic diseases are noted in 76% of CVID patients and 100% of patients with selective immunodeficiencies. Immunoglobulin levels were extremely low in XLA and decreased in CVID patients. Three SCID patients had decreased mean absolute lymphocyte counts of 290/mm3. Long-term complications included bronchiectasis in 2 XLA patients, 2 CVID patients and 1 patient with selective immunodeficiency; short stature in one of each XLA, SCID, and CVID patients respectively; poor school performance in 2 SCID patients and 1 XLA patient; and hemolytic anemia in 1 CVID patient. We concluded that in addition to a thorough physical examination, a family history of early death from infection and past history of neonatal hyperbilirubinemia, are crucial in evaluating a patient with suspicious primary hypogammaglobulinemia. The associated symptoms of primary hypogammaglobulinemia, such as recurrent sinopulmonary infections, prolonged fever and allergic diseases, are also diagnostic clues. In the treatment of hypogammaglobulinemia, early and regular high doses of Intravenous immunoglobulin (IVIG) supplement may avoid the development or decrease the severity of bronchiectasis.
 ...
PMID:Immunological and clinical features of pediatric patients with primary hypogammaglobulinemia in Taiwan. 1536 55


<< Previous 1 2 3 4 5 6 7 8 9 Next >>