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)

X-linked agammaglobulinemia (XLA) is an immunodeficiency disorder caused by mutations in the gene coding for Bruton's tyrosine kinase (BTK). In this study we investigated 10 male patients with XLA-compatible phenotype (agammaglobulinemia and undetectable B cells in peripheral blood) from 9 unrelated Central European families. We identified seven different mutations, six of which were novel. One previously described point mutation caused a premature stop codon (p.C464X), two point mutations resulted in amino acid exchanges (p.W588R; p.G419E), and two point mutations affected splice sites (c.305-1G>A; c.391+1G>A). We further detected one deletion (c.1921_1927del CGTCCCA) and one large duplication. The duplication resulted from Alu element-induced unequal homologous recombination, which was only detectable by extended analysis of cDNA, while direct sequencing of genomic DNA gave a false negative result. Western blot analysis revealed that the patients with the p.W588R and the p.G419E amino acid substitutions, respectively, produced full length BTK, but in clearly diminished amounts. The patient with the 7bp deletion expressed low amounts of protein which might represent truncated BTK. All other genomic alterations resulted in complete loss of BTK protein. In two patients from unrelated families BTK protein expression was normal and no Btk gene mutation was detected. The results of this study further substantiate the importance of using elaborate molecular analysis with different detection techniques to obtain an explicit molecular diagnosis in patients with suspected XLA.
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PMID:Characterization of novel Bruton's tyrosine kinase gene mutations in Central European patients with agammaglobulinemia. 1704 52

Markers of humoral and cellular immunity in 16 patients with vaccine-associated paralytic poliomyelitis (VAPP) were evaluated. Signs of immunodeficiency (decrease of T- and B-lymphocytes counts, impaired synthesis of immunoglobulins, defects of phagocytosis, decrease of NK number) were revealed in all of the patients. Majority of them (81.3%) had defects in humoral immunity. Decrease of CD31, CD4+ and CD8+ was detected in 86.7, 35.7 and 91.7% of the patients respectively. Study of serum immunoglobulins performed in 15 patients showed decrease of IgG, IgM and IgA levels in 6 (40%), 1 (6.7%) and 6 (40%) of the patients respectively. Agammaglobulinemia was diagnosed in one patient in which only trace quantities of IgA and IgG were detected and IgM level was well below the normal. Congenital deficiency of IgA was diagnosed in 3 children. Majority of the children (11 from 12) had comorbidities (frequent respiratory infections, dermatitis, changes of intestinal microflora). Thus, immunocompromised condition of a child is a risk factor for VAPP after administration of alive oral poliovaccine.
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PMID:[Cellular and humoral immunodeficiency in children with vaccine-associated paralytic poliomyelitis]. 1729 80

One of the most prevalent manifestations of primary antibody deficiencies is gastrointestinal disorders. In this study we reviewed 83 patients including 25 with X-Linked agammaglobulinemia, 40 with common variable immunodeficiency, 14 with IgA deficiency and 4 with IgG subclass deficiency. The mean age of patients was 10 year (1-28 years). The ratio of male to female was 1.5. Gastrointestinal system was affected in more than half (57.8%) of them. The most common symptom was diarrhea (56.6%) and the most prevalent pathogen was. G. Lamblia. Other disorders were chronic active hepatitis in 6 patients, ulcerative colitis in 2, small intestinal villus atrophy in 5, nodular lymphoid hyperplasia of small intestine in 3 and chronic gastritis in 4 patients. One patient suffered from abdominal lymphoma. We found a direct correlation between failure of patients to thrive and the duration of the delay in diagnosing the underlying disease. This difference was more apparent in those with both antibody deficiency and gastrointestinal involvement.
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PMID:A review of gastrointestinal disorders in patients with primary antibody immunodeficiencies during a 10-year period (1990-2000), in children hospital medical center. 1730 60

Recurrent infections are a consequence of a series of genetic diseases characterized by deficiency in the immunological response. One of these diseases is the agammaglobulinemia, which is characterized by the basic defect in the maturation of lymphocytes B. The carrier of this kind of immunodeficiency, which is linked to the X (XLA) chromosome, has had primary pneumonias that have evolved into secondary pneumonias (chronic lungs with sequelae) after the third or fourth year of life. The clinical and rehabilitative quest for prophylaxis against the XLA immunodeficiency is accomplished in order to avoid the evolution of the bacterial infection into sequelae and loss of pulmonary function, which propitiates the recurrence of the disease and deteriorates the life quality of the patient. Forty cases of recurrent respiratory infections were studied. Some of them were associated with primary respiratory diseases without investigation of serum immunoglobulins and some were not. Casuistics was performed according to data from medical records with pertinent treatments collected from January 1997 to September 2004 at the Specialized Physiotherapy Center. Age average was 2.7 years of life. It is statistically impossible to precise results concerning only the immunosuppressed patients due to the lack of specific diagnosis. That is explained by the fact that recurrent XLA pneumonias may be attributed to the gastroesophageal reflux disease or to bronchial asthma. However, the improved results showed by the pulmonary function as preventive strategy were attributed to the respiratory physiotherapy, since intravenous immunoglobulin replacement therapies were not performed. Respiratory physiotherapy acts as a supportive factor in the healing process and occupies a fundamental role in the prophylaxis against recurrent respiratory clinical features, especially those of obstructive and secretionary characteristics.
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PMID:Recurrent pneumonia caused by genetic immunodeficiency: a prophylactic and rehabilitative approach. 1768 29

Agammaglobulinemia is a rare primary immunodeficiency characterized by an early block of B cell development in the bone marrow, resulting in the absence of peripheral B cells and low/absent immunoglobulin serum levels. So far, mutations in Btk, mu heavy chain, surrogate light chain, Igalpha, and B cell linker have been found in 85-90% of patients with agammaglobulinemia. We report on the first patient with agammaglobulinemia caused by a homozygous nonsense mutation in Igbeta, which is a transmembrane protein that associates with Igalpha as part of the preBCR complex. Transfection experiments using Drosophila melanogaster S2 Schneider cells showed that the mutant Igbeta is no longer able to associate with Igalpha, and that assembly of the BCR complex on the cell surface is abrogated. The essential role of Igbeta for human B cell development was further demonstrated by immunofluorescence analysis of the patient's bone marrow, which showed a complete block of B cell development at the pro-B to preB transition. These results indicate that mutations in Igbeta can cause agammaglobulinemia in man.
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PMID:Mutations of the Igbeta gene cause agammaglobulinemia in man. 1770 24

X-linked agammaglobulinemia (XLA) is a humoral primary immunodeficiency in which affected patients have very low levels of peripheral B cells and a profound deficiency of all immunoglobulin isotypes. Mutations in the gene encoding for Bruton's tyrosine kinase (Btk) are responsible for most of the agammaglobulinemia. In this work, 14 Btk mutations responsible of causing XLA are described; eight of which are novel and six are mutations previously reported. Seven of the mutations were due to deletions and insertions of exons and introns, respectively, which suggest splicing defects. The others were missense mutations, five of which affect arginine residues and have been described, and two new which affect leucine and glutamine residues (L111P and E605G). Most of these mutations were located at the kinase domain of Btk and, less frequently, they were found in PH and SH2 domains. Protein expression was also affected since most of the patients did not express or express very low Btk.
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PMID:Characterization of Bruton's tyrosine kinase mutations in Mexican patients with X-linked agammaglobulinemia. 1776 9

Dr. Robert A. Good and the March of Dimes Birth Defects Foundation maintained a close association for a quarter century in the fight against immunodeficiency diseases. The March of Dimes, whose mission is to prevent birth defects, premature birth, and infant mortality, awarded an initial grant to Dr. Good in 1960 to conduct basic clinical and experimental studies on arthritis and collagen diseases. By 1966, this support broadened to include Dr. Good's research on agammaglobulinemia, ataxia telangiectasia, Chediak-Higashi disease, and Wiskott-Aldrich syndrome. Dr. Good led three historic March of Dimes conferences on immunodeficiency and, in 1968, conducted the first bone marrow transplant to correct an immunological birth defect, memorialized by the March of Dimes in its educational film, Decision (1970). March of Dimes grants to Dr. Good for his research in cellular engineering to genetically correct the defined birth defects approached $1 million for the period 1960-1985.
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PMID:Robert A. Good, the March of Dimes, and immunodeficiency: an historical perspective. 1791 9

BTK deficiency is a primary immunodeficiency disease characterized by the absence of circulating B cells and agammaglobulinemia. While recurrent bacterial infections are the most common manifestations, symptoms of allergy and asthma are rare. We present the case of a 7-year-old boy who presented with asthma symptoms, allergic rhinitis, and severe papular urticaria. He had a positive skin prick test to aeroallergens and food allergens. However, further laboratory tests revealed a low number of B cells and decreased serum levels of all immunoglobulin isotypes. Molecular analysis revealed a mutation in the BTK gene. Although patients with BTK deficiency seem to be protected from atopy, our patient had allergic symptoms suggesting a bias toward a type 2 helper T cell pattern in this case. Primary antibody deficiency should be considered in the differential diagnosis of pediatric allergy and asthma when respiratory infection persists despite appropriate treatment.
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PMID:Asthma and allergic rhinitis in a patient with BTK deficiency. 1871 39

Secondary thrombocytopenia may result from autoimmune diseases, lymphoproliferative disorders, infections, myelodysplastic syndromes, common variable immunodeficiency, agammaglobulinemia, hypogammaglobulinemia, immunoglobulin A deficiency, and drugs. The presence of thrombocytopenia may result from chronic infections with hepatitis C virus (HCV), human immunodeficiency virus (HIV), and Helicobacter pylori and should be considered in the differential diagnosis of immune thrombocytopenic purpura (ITP). Studies have shown that upon diagnosis of infections, treatment of the primary disease allows for stabilization of platelet counts. Antiviral therapy with highly active antiretroviral therapy (HAART) for HIV has aided in platelet recovery with a corresponding decrease in circulating viral load. In some cases, the use of a thrombopoietin (TPO) agonist, eltrombopag, normalizes platelet levels in patients with these infections. Thrombocytopenia in the absence of other disease symptoms requires screening for H pylori, especially in regions where there is a high prevalence of the disease, such as in Japan, and in cases where platelets have normalized following eradication therapy. In other regions where these infections are not prevalent, such testing is controversial.
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PMID:Therapeutic strategies for hepatitis- and other infection-related immune thrombocytopenias. 1924 29

X-linked Agammaglobulinemia (XLA) is a hereditary immunodeficiency, characterized by an early onset of recurrent bacterial infections, hypogammaglobulinemia and markedly reduced B lymphocytes number. In order to determine the association of neutropenia among Iranian patients with XLA, hospital records of 30 patients with confirmed XLA in Children Medical Center Hospital, were reviewed. Eight out of 30 XLA patients (26.7%) developed neutropenia during the course of the disease. In two patients, episodes of neutropenia were identified before or at the time of diagnosis of XLA. Other six patients whom were not visited regularly and did not receive periodical immunoglobulin replacement therapy experienced neutropenia after diagnosis of XLA. Neutropenia in XLA is mainly associated with infection and is resolved with intravenous immunoglobulin replacement and antibiotics therapy.
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PMID:Neutropenia associated with X-linked Agammaglobulinemia in an Iranian referral center. 1927 58


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