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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Knowledge of the molecular defects responsible for some primary immunodeficiency diseases (PIDs) offers undoubted advantages in establishing a reliable diagnosis. Such knowledge would allow us not only to establish a prognosis but also to instigate the most appropriate therapy. After molecular diagnosis, some patients could benefit from gene therapy. However, apart from the diagnosis of the disease, molecular biological techniques also enable more reliable identification of carriers and, when suggested by the family history and when the familial defect is already known, prenatal diagnosis will also be possible, thus establishing the earliest possible treatment. Using the single-stranded conformational polymorphism technique followed by direct sequencing, we found 22 different mutations in 22 patients from unrelated families and with a phenotype compatible with x-linked agammaglobulinemia. Fourteen of these are new, previously undescribed mutations and the remaining eight are already included in the data base (http://www.uta.fi/imt/bioinfo/Btkbase). Analysis of the female carrier was performed in all the mothers and the mutation was de novo in only one patient. Study of the BtK gene enabled differential diagnosis with common variable immunodeficiency disease in some patients who showed absent or very low lymphocyte B counts as well as forms of autosomal recessive agammaglobulinemia. Using the same techniques, we were able to identify mutations in the CD40 ligand gene in three families in which one of the members had clinical and biological phenotype compatible with X-linked hyper-IgM. Molecular diagnosis was very useful in identifying carriers in these families as well as in making the differential diagnosis among patients with common variable immunodeficiency disease. Purely on this were we able to provide appropriate genetic counseling.
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PMID:[Molecular diagnosis of primary immunodeficiencies]. 1143 83

Periodically the World Health Organization and currently the International Union of Immunology Societies publish a classification of primary immunodeficiency diseases (PID) that includes diagnostic and therapeutic guidelines. The latest of these publications dates from 1999 and includes a new group of PID, the proliferative autoimmune syndromes. Furthermore, new forms of severe combined immunodeficiency (SCID) and of recessive autosomal agammaglobulinemia are described. From the publication of this classification until the end of the year 2000 a minimum of three new PIDs have been described and a further two should probably be added. Progress in the molecular biology of these diseases has given rise not only to more accurate diagnosis but also to greater insight into the clinical spectrum of these diseases. A mutation or deletion in a gene can provoke the complete absence of its product; sometimes expression is partial or normal but functional activity is absent or defective. In certain cases, partial or defective activity causes variant forms of the disease presenting symptomatology or atypical cellular phenotype. In other cases, this is not cause of the variant form, which can appear in interfamilial cases sharing the same mutation. In these cases, these differences can be attributed to environmental factors or to other genes able to modify the affected gene. In this article we provide examples of variant forms in several PIDs. Some are late onset forms, such as X-linked agammaglobulinemias diagnosed in adults, since until diagnosis, clinical symptomatology was minimal. In adenosine-deaminase deficiency, a serious and highly lymphoproliferative form of SCID, patients have been described whose symptomatology began after the age of 20 years. Another SCID, RAG1 and RAG2 recombinase deficiency, may produce a typical form with a characteristic T-B-NK + phenotype, Omenn's syndrome, or forms with an unexpected T-B + NK + phenotype. Deficiency in common gamma chain receptor for IL-2 may produce phenotypical variants that can lead to diagnostic error. X-linked lymphoproliferative syndrome may present as fulminant infectious mononucleosis, as leukemia or lymphoma or as hipo- or agammaglobulinemia. Possibly, some patients diagnosed with common variable immunodeficiency or with x-linked agammaglobulinemia do in fact have this syndrome. Chronic granulomatous disease is usually of early-onset, but late-onset forms have been described. In one case the first clinical manifestation was produced when the patient was 60 years old. The above examples serve to highlight that, even though PIDs are usually suspected by pediatricians, in some cases the diagnosis may be missed by internists or non-pediatricians. Moreover, the clinical and laboratory findings of these variant forms must be determined to carry out an early diagnosis, which is essential for a favorable therapeutic outcome.
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PMID:[Primary immunodeficiencies. Clinical features and variant forms]. 1143 82

A 12-year-old Quarter Horse mare that was nonresponsive to medical treatment was evaluated for chronic respiratory disease and hepatobiliary disease. Serum immunoglobulin concentrations were measured by use of radial immunodiffusion that revealed trace to nondetectable concentrations of IgG, IgG(T), IgM, and IgA. Use of serum protein electrophoresis confirmed agammaglobulinemia by the absence of the expected peak in the gamma region. In addition, vaccination with tetanus toxoid did not result in specific immunoglobulin production. Flow cytometric analysis of blood lymphocyte subpopulations revealed the absence of B cells in blood. Immunohistochemical analysis of tissue sections revealed the absence of B lymphocytes in bone marrow and spleen, with occasional B cells in the peripheral lymph nodes. Blood lymphocyte proliferation assays revealed weak responses to pokeweed mitogen and no response to stimulation with lipopolysaccharide. Considering the age and sex of the horse, results of the immunologic tests suggested a diagnosis of common variable immunodeficiency.
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PMID:Common variable immunodeficiency in a horse. 1241 96

Epidemiological studies have shown wide geographical and racial variation in the prevalence and patterns of immunodeficiency disorders. To determine the frequency of primary immunodeficiencies (PID) in Iran, the Iranian Primary Immunodeficiency Registry (IPIDR) was organized in 1999. We extracted the patient's data, by using a uniform questionnaire from their hospital records. The diagnosis of patients was based on WHO criteria. By now, 440 patients with PID, who were observed during a period of 20 years, have been registered in our registry. Among these patients, the following frequencies were found: predominantly antibody deficiency in 45.9% of patients (n = 202), phagocytic disorders in 29.09% (n = 128), T-cell disorders in 24.31% (n = 107), and complement deficiencies in 0.68% (n = 3). Common variable immunodeficiency was the most frequent disorder (n = 98), followed by chronic granulomatous disease (n = 86), ataxia telangiectasia (n = 48), x-linked agammaglobulinemia (n = 45), selective IgA deficiency (n = 42), combined immunodeficiency (n = 15), and severe combined immunodeficiency (n = 14). This study revealed that antibody deficiencies is the most frequently diagnosed primary immunodeficiency disorder in our patients, which is similar to that observed in other registries. A comparative study shows some differences between our results and other registries.
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PMID:Primary immunodeficiency in Iran: first report of the National Registry of PID in Children and Adults. 1246 37

Although people with bacterial meningitis lack adequate protective antibody against the invading pathogen, most do not have an underlying immunodeficiency. Certain comorbid conditions increase the risk for development of bacterial sepsis and meningitis. In addition, certain congenital complement deficiencies, defects of antibody production, or asplenia may be first recognized by the occurrence of bacterial meningitis, particularly when it occurs in infants or young children. Deficiencies of the terminal components of complement (C5-C9) or properdin have been associated with recurrent or invasive neisserial infections, and asplenia, agammaglobulinemia, and deficiencies of the early components of complement (e.g., C1-C3) are associated with risks of infections caused by Streptococcus pneumoniae, Haemophilus influenzae, and meningococci. The presence of congenital or acquired immunodeficiencies should be considered in persons who present with bacterial meningitis on the basis of the etiology, clinical epidemiology, and presence of other risk factors.
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PMID:Indications for the immunological evaluation of patients with meningitis. 1252 51

Only one human disease that involves Mendelian inheritance of immunodeficiency and aberrant DNA methylation has been identified. This is a rare chromosome breakage disease called the immunodeficiency, centromeric region instability, and facial anomalies syndrome (ICF). Its diagnostic characteristics are agammaglobulinemia with B cells as well as DNA rearrangements targeted to the centromere-adjacent heterochromatic region (qh) of chromosomes 1, 16, and sometimes 9 in mitogen-stimulated lymphocytes. These rearrangement-prone regions show DNA hypomethylation in all examined ICF cell populations. This review summarizes our knowledge about the immunological symptoms of ICF; the nature of DNMT3B mutations in ICF patients; the phenotypes of DNA hypomethylation mutants in humans, mice, and Arabidopsis; the epigenetics of ICF; and ICF-specific RNA expression and cell-surface antigen expression in lymphoblastoid cell lines. Comparisons of ICF and control lymphoblastoid cell lines and ICF patients' symptoms suggest an involvement of DNA methylation in the late stages of lymphocyte maturation.
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PMID:The ICF syndrome, a DNA methyltransferase 3B deficiency and immunodeficiency disease. 1458 72

Immunodeficiency, centromeric region instability, and facial anomalies (ICF) syndrome is a rare autosomal recessive disease. Mutations in the DNA methyltransferase 3B (DNMT3B) gene are responsible for most ICF cases reported. We investigated the B-cell defects associated with agammaglobulinemia in this syndrome by analyzing primary B cells from 4 ICF patients. ICF peripheral blood (PB) contains only naive B cells; memory and gut plasma cells are absent. Naive ICF B cells bear potentially autoreactive long heavy chain variable regions complementarity determining region 3's (V(H)CDR3's) enriched with positively charged residues, in contrast to normal PB transitional and mature B cells, indicating that negative selection is impaired in patients. Like anergic B cells in transgenic models, newly generated and immature B cells accumulate in PB. Moreover, these cells secrete immunoglobulins and exhibit increased apoptosis following in vitro activation. However, they are able to up-regulate CD86, indicating that mechanisms other than anergy participate in silencing of ICF B cells. One patient without DNMT3B mutations shows differences in immunoglobulin E (IgE) switch induction, suggesting that immunodeficiency could vary with the genetic origin of the syndrome. In this study, we determined that negative selection breakdown and peripheral B-cell maturation blockage contribute to agammaglobulinemia in the ICF syndrome.
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PMID:Defective B-cell-negative selection and terminal differentiation in the ICF syndrome. 1464 8

X linked agammaglobulinemia (XLA) is an immunodeficiency disease caused by mutations in the gene coding for Bruton's agammaglobulinemia tyrosine kinase (BTK), that is involved in signal transduction pathways regulating survival, activation, proliferation, and differentiation of B lineage lymphoid cells. XLA is a primary immunodeficiency disorder characterized by lack of mature, circulating B lymphocytes, and recurrent infections. Using Single Strand Conformation Polymorphism (SSCP) followed by direct sequencing we investigated 57 patients with XLA phenotype, with or without a positive family history, from 52 unrelated families enrolled in the Italian XLA Multicenter Clinical Study. We have identified 25 recurrent mutations, 22 novel mutations including one large deletion comprising the coding sequence from exon 11 to 18. Among the mutations identified, three were detected in different unrelated families, whereas all the others were private mutations.
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PMID:BTK: 22 novel and 25 recurrent mutations in European patients with X-linked agammaglobulinemia. 1497 89

In the fifty years since Ogden Bruton discovered agammaglobulinemia, more than 100 additional immunodeficiency syndromes have been described. These disorders may involve one or more components of the immune system, including T, B, and NK lymphocytes; phagocytic cells; and complement proteins. Most are recessive traits, some of which are caused by mutations in genes on the X chromosome, others in genes on autosomal chromosomes. Until the past decade, there was little insight into the fundamental problems underlying a majority of these conditions. Many of the primary immunodeficiency diseases have now been mapped to specific chromosomal locations, and the fundamental biologic errors have been identified in more than 3 dozen. Within the past decade the molecular bases of 7 X-linked immunodeficiency disorders have been reported: X-linked immunodeficiency with Hyper IgM, X-linked lymphoproliferative disease, X-linked agammaglobulinemia, X-linked severe combined immunodeficiency, the Wiskott-Aldrich syndrome, nuclear factor kappaB essential modulator (NEMO or IKKg), and the immune dysregulation polyendocrinopathy (IPEX) syndrome. The abnormal genes in X-linked chronic granulomatous disease (CGD) and properdin deficiency had been identified several years earlier. In addition, there are now many autosomal recessive immunodeficiencies for which the molecular bases have been discovered. These new advances will be reviewed, with particular emphasis on the pulmonary complications of some of these diseases. In some cases there are unique features of lung abnormalities in specific defects. Infections obviously account for most of these complications, but the host reaction to infection often leads to characteristic findings that can be helpful diagnostically. Finally, advances in treatment of the underlying diseases as well as their infectious complications will be covered.
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PMID:Pulmonary complications of primary immunodeficiencies. 1498 Feb 76

Agammaglobulinemia is characterized by failure of B-cell differentiation (hypogammaglobulinemia) and increased susceptibility to bacterial infections. The present study was set up in order to evaluate the effectiveness of intravenous immunoglobulin (IVIG) treatment on the incidence of pneumonia in patients with agammaglobulinemia. We carried out chart reviews of 23 patients with agammaglobulinemia (mean age 11.5+/-5.4 years), who had been observed in a 22-year period (July 1981-January 2003) in Iran's referral center for primary immunodeficiency disorders. Nineteen of these 23 (82.5%) had been infected with pneumonia at least once before receiving the immunoglobulin treatment and 11 of them had experienced multiple episodes. During treatment with gamma-globulin - over a mean period of 6.8+/-4.1 years (range: 0.8-15.3 years) - the incidence of pneumonia requiring treatment or hospitalization decreased from 0.82 to 0.12 per patient per year (P=0.006). During IVIG replacement, hospitalization due to pneumonia decreased from 0.58 to 0.05 per patient per year (P=0.08) and the immunoglobulin G level (mean+/-S.D.) changed from 66.2+/-63.9 (range: 0-210 mg dl(-1)) to 552.4+/-199.1 (range: 136-942 mg dl(-1)) (P<0.001). Treatment of agammaglobulinemia with IVIG significantly reduced the incidence of pneumonia and hospital admission. Intensive management and regular monitoring is required in order to fully prevent severe respiratory complications.
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PMID:Efficacy of intravenous immunoglobulin on the prevention of pneumonia in patients with agammaglobulinemia. 1498 29


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