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

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.
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PMID:Immunological and clinical features of pediatric patients with primary hypogammaglobulinemia in Taiwan. 1536 55

The vast majority of known primary immunodeficiencies (PIDs) are autosomal or X-linked recessive Mendelian traits. Only four classical primary immunodeficiencies are thought to be autosomal-dominant, three of which still lack a well-defined genetic etiology: isolated congenital asplenia, isolated chronic mucocutaneous candidiasis, and hyper IgE syndrome. The large deletions on chromosome 22q11.2 associated with Di George syndrome suggest that this disease may be dominant but not Mendelian, possibly involving several genes. The clinical and genetic features of six novel autosomal-dominant primary immunodeficiencies have however been described in recent years. These primary immunodeficiencies are caused by germline mutations in seven genes: ELA2, encoding a neutrophil elastase, and GFI1, encoding a regulator of ELA2 (mutations associated with severe congenital neutropenia); CXCR4, encoding a chemokine receptor (warts, hypogammaglobulinemia, infections and myelokathexis syndrome); LCRR8, encoding a key protein for B-cell development (agammaglobulinemia); IFNGR1, encoding the ligand-binding chain of the interferon-gamma receptor; STAT1, encoding the signal transducer and activator of transcription 1 downstream from interferon-gammaR1 (Mendelian susceptibility to mycobacterial diseases); and IKBA, encoding IkappaBalpha, the inhibitor alpha of NF-kappaB (anhidrotic ectodermal dysplasia with immunodeficiency). These recent data suggest that many more autosomal-dominant PIDs are likely to be identified in the near future.
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PMID:Autosomal-dominant primary immunodeficiencies. 1560 87

Agammaglobulinemia is the most common primary immunodeficiency, with an incidence of approximately 1 in 250,000 males in the United States. These patients are at risk for frequent recurrent infections, which may become fatal if untreated. Patients have increased susceptibility to encapsulated pyogenic bacteria. Haemophilus influenzae is second only to Streptococcus pneumoniae as the bacteria most frequently implicated in infections in these patients. We present a case involving an adolescent boy with X-linked agammaglobulinemia and H influenzae cervical adenopathy, confirmed twice by culture. We correlate the clinical, microbiologic, and histologic findings. Owing to the severity of infections in this population, surgical intervention is more common than in the immunocompetent population. This description may help the pathologist in considering a differential diagnosis when examining a diagnostic lymph node biopsy in these patients.
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PMID:Haemophilus influenzae lymphadenopathy in a patient with agammaglobulinemia: clinical-histologic-microbiologic correlation and review of the literature. 1562 87

Some 5% to 10% of all infants and toddlers suffer from four or more episodes of otitis per year. Usually, this is a temporary problem that resolves with increasing age. In a minority of cases, otitis episodes are frequent or have an abnormal course, with complications such as mastoiditis. In these cases, immunologic screening is indicated, to exclude an immunodeficiency. Agammaglobulinemia or hypogammaglobulinemia is rare among these patients. Other immune defects that occur more often are deficient or lowered immunoglobulin (Ig)A or decreased levels of one or more IgG subclass, in particular IgG2. The specific antibody response to bacterial capsular polysaccharides often is disturbed. These findings can give direction to the treatment of children with frequent, recurrent otitis.
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PMID:Immunologic screening of children with recurrent otitis media. 1596 72

Primary immune deficiencies (PIDs) are characterized by functional and/or quantitative abnormalities of one or more immune system components. Several bone and joint abnormalities can occur in patients with PID, with arthritis being the most common. Joint manifestations, of which arthritis is the most common, occur chiefly in humoral PIDs (agammaglobulinemia, common variable immunodeficiency, hyper-IgM syndromes, and IgA deficiency) and occasionally in other PIDs (chronic granulomatous disease and Wiskott-Aldrich syndrome). Monoarthritis or oligoarthritis is the usual pattern, although polyarthritis may occur, occasionally with nodules suggesting rheumatoid arthritis. Arthritis in patients with PID is usually infectious in nature, the most common causative organism being Mycoplasma, followed by Staphylococcus, Streptococcus, and Haemophilus. These bacteria can induce not only synovial infections, but also aseptic arthritogenic inflammatory responses. Arthritis having no demonstrable relation to chronic infection has been reported also and ascribed to dysimmunity-driven mechanisms that exhibit a number of specific features. Bone lesions are far less common and usually due to infections complicating humoral PID. Distinctive bone manifestations occur in a number of rare PIDs (e.g., hyper-IgE syndrome and Di George syndrome) and in syndromes characterized by spondyloepiphyseal dysplasia. Familiarity with PID syndromes both enhances the diagnostic capabilities of physicians and provides insight into the pathophysiology of bone and joint abnormalities associated with immune dysfunction. In children and occasionally in adults, a combination of bone and/or joint manifestations and hypogammaglobulinemia may indicate PID. When there is no evidence of lymphoproliferative disease, infection, or iatrogenic complications, investigations for PID should be obtained. PID-related arthritis is a unique model for studying the pathogenesis of presumably postinfectious arthritis and of inflammatory joint diseases including rheumatoid arthritis.
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PMID:Bone and joint disease associated with primary immune deficiencies. 1637 4

The pace of discovery in primary immunodeficiency continues to accelerate. In particular, lymphocyte defects have been the source of the most impressive expansion in recent years. Novel forms of agammaglobulinemia, class-switch defects, and T-B(+) severe combined immunodeficiency have been described. Little by little, the genetic heterogeneity of the common variable immunodeficiency and IgA deficiency phenotypes continues to be unraveled as new molecular defects have been reported in these patients as well. The phenotypic spectrum of DiGeorge syndrome has been further developed, along with promising advances in therapy. Defects of nuclear factor kappaB regulation and Toll-like receptor signaling have been described, along with defects of chemokine receptors and cytoplasmic proteases. Clinically defined immunodeficiencies, such as hyper-IgE syndrome and idiopathic CD4 lymphocytopenia, are also discussed. Finally, significant adverse effects in some patients have tempered initial enthusiasm for gene therapy.
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PMID:2. Update on primary immunodeficiency diseases. 1645 42

The ATP-dependent DNA helicase Q4 (RECQL4) belongs to a family of conserved RECQ helicases that are felt to be important in maintaining chromosomal integrity (Kitao et al., 1998, Genomics: 54 (3): 443-452). Deletions in the RECQL4 gene located on chromosome 8 region q24.3 have been associated with Rothmund-Thomson syndrome (RTS, OMIM 268400), a condition characterized by poikiloderma, sparse hair, small stature, skeletal abnormalities, cataracts and an increased risk of malignancy. We present a patient with a molecularly confirmed diagnosis of RTS with two unique genetic alterations in RECQL4 (IVS16-2A>T and IVS2+27_51del25), who at the age of 7 months nearly succumbed to Pneumocystis carinii pneumonia. Evaluation of his immune system demonstrated a T- B+ NK- phenotype with agammaglobulinemia consistent with combined immunodeficiency (CID). Studies to evaluate for known genetic causes of CID were not revealing. The patient received an umbilical cord blood (UCB) transplant with complete immune reconstitution. This report represents the first description of a CID phenotype and UCB transplantation in a patient with RTS.
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PMID:Successful umbilical cord blood stem cell transplantation in a patient with Rothmund-Thomson syndrome and combined immunodeficiency. 1663 Jan 67

Immunoglobulins (Igs) or antibodies (Abs) are the principal operators of the adaptive humoral immune response. For optimum functional activity they acquire an optimized structure for antigen (Ag) recognition, precipitation, agglutination, phagocytosis (IgG1/3 and IgA), cytotoxicity (IgG1/3), transport through mucosa (IgA and IgM) and placenta (IgG1/3), complement activation (IgG1/3 and IgM) and release of inflammatory mediators (IgE). A diversity with potentially up to 10(15) different Ab specificities is generated during Ag-independent B cell development in the bone marrow by combinatorial V-D-J joining, creation of junctional diversity, and combinatorial association of L and H chains. Furthermore,Ab variety is created during Ag-dependent B cell maturation in peripheral lymphatic tissues by isotype class switching and somatic hypermutation. Two types of enzymes play a key role in Ab diverseness, i. e., the products of recombination-activating genes RAG1 and RAG2 and the affinity induced deaminase (AID). The prevailing adult-type B2 cells provide the basis for the acquired humoral immune response characterized by Ab production,Ag processing and presentation, immunological memory and tolerance along with the generation of the anti-idiotype network,whereas the fetal-type B1 cells may play a role in innate immunity and autoimmunity. Impairment of B cell immunity includes immunodeficiency (agammaglobulinemia), malignant transformation (leukemia, lymphoma, plasmocytoma) and immune dysregulation (allergy, autoimmunity). The diagnostic relevance of Abs comprises classical serology (immunoprecipitation, agglutination, complement binding, RIA, ELISA), immunocytochemistry and immunohistochemistry, immunofluorescence (microscopic and flow cytometric), cytotoxicity tests, immunoblots, immunospot assays and immunoabsorption (affinity chromatography). Therapeutic application of Abs (passive immunization) is directed against infections, intoxications, solid tumors, leukemias and lymphomas, graft rejection and graft-versus-host reaction, hemolytic anemia, and autoimmune diseases. The generation of genetically engineered monoclonal Abs (mAbs) has revolutionized the diagnostic and therapeutic potential of Abs in almost all disciplines of modern medicine.
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PMID:Immunoglobulins--basic considerations. 1699 62

Bruton's disease is the most frequently primary X-linked immunodeficiency. Bruton's tyrosine kinase (Btk) is encoded by the XLA gene that when mutated causes bruton's disease. This protein acts in multiple intracellular signaling pathways where the BCR (B-cell receptor) pathway is the most elucidated. Moreover 400 mutations were found and identified as responsible for B-cells differentiation block; consequences are a lack of B-cells in peripheral blood and hypo/agammaglobulinemia. Thus, patients are more susceptible to early and recurring infections occurring before the age of one year. Laboratory testing allow differential diagnosis among primary immunodeficiencies in which others hypogammaglobulinemia. Genetic analyses help physicians for clinical and biological diagnosis, and allow prenatal diagnosis for patient's family. Patient's management is based upon polyclonal immunoglobulin supplementation, infectious diseases prevention and genetic advice.
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PMID:[Primary immunodeficiencies and Bruton's disease genetic analysis: which prospects offers this genetic diagnosis?]. 1704 Aug 72

Bruton's disease is the most frequently primary X-linked immunodeficiency. Patients are more susceptible to early and recurring infections associated with hypo/agammaglobulinemia and a severe B-cell deficiency. Moreover, 400 mutations were found in the XLA gene which codes the Btk tyrosine kinase and were identified as responsible for Bruton's disease. Genetic study was carried out with one group of patients named NECKER, composed by five XLA patients and two parents whose XLA gene was sequenced by an Italian crew. Results were obtained by PCR of 19 exons and initial/terminal intron's parts, followed by PCR-sequencing with universal primers and sequencing. The results from this study allowed the validation of the sequencing technique by comparing NECKER group data (equivalent results with Italian data). In addition, the mutation multiplicity (described or not, coding/non coding) need an exact analysis that should be given to clinicians through clear and trustful results. In this way, a strategy to analyse untreated results was created based on the mutation type. The genetic analysis could help physicians for uncertain diagnosis in immune defficiencies, allows proposing a genetic advice to the patient's family and the construction of a data base permits a best understanding of this disease.
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PMID:[Validation of a Bruton's disease genetic analysis method]. 1704 Aug 75


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