Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A young woman with DiGeorge anomaly showed normal immune tests as a child and did not experience the symptoms of profound T cell immunodeficiency. However, she had chronic pulmonary infections which led to bronchiectasis. At age 14, she developed an Epstein-Barr virus-induced lymphoma and her T cell function tests were markedly abnormal. After intensive chemotherapy, she received an organ-cultured thymus transplant but because of an abnormally high EBV DNA titer was also given autologous EBV-specific cytotoxic T cells, prepared prior to transplant. Titers fell from 80,000 genome copies/mg DNA to 2000 within 6 weeks. She was clinically well and her T cell tests improved. Sixteen months after the transplant, however, her tumor returned; EBV DNA levels had risen to 40,000 copies/mg DNA. She again received autologous EBV-specific cytotoxic T lymphocytes and valcyclovir and Cytogam as well. Her tumor resolved on this therapy and she has remained well to this date, 29 months after the recurrence. T cell tests, which had deteriorated with the recurrence of the tumor, now show normal responses. This experience records a number of unique features of thymus transplantation. This is the first recorded successful thymus transplant in a patient with partial T cell immunity and thus expands the potential of this treatment modality to patients other than infants with complete DiGeorge anomaly. The patient demonstrates cytotoxic activity against mouse cells, demonstrating the ability to respond to a new antigen which requires host antigen presenting cells. Measurement of alpha 1 TRECs (T cell receptor excision circles) shows evidence of increasing and sustained thymopoiesis since the transplant at a level consistent with the age of the transplant donor rather than that of the recipient.
 ...
PMID:Correction of DiGeorge anomaly with EBV-induced lymphoma by transplantation of organ-cultured thymus and Epstein-Barr-specific cytotoxic T lymphocytes. 1114 27

Deletion of chromosome 22q11 concerns nearly 1/5.000 births, and is the most frequent interstitial microdeletion. The deletion generates various phenotypes which were initially regarded as distinct syndromes. 1) Di George syndrome was described in 1962 by immunologists, and associates thymic and parathyroid hypoplasia, cardiac malformation, and dysmorphic face; the prognosis is severe, as Di George syndrome is a life-threatening condition. 2) The velocardiofacial syndrome was described in 1978 by stomatologists, and associates palate abnormalities, cardiac malformations, dysmorphic faces, and learning disabilities. 3) The Takao syndrome was described in the late seventies by cardiologists as a clinical condition associating cardiac abnormalities and dysmorphic faces. During the nineties, a common molecular etiology was identified, and a new name proposed: CATCH 22, an acronyme for Cardiac abnormalities, Abnormal face, Thymic hypoplasia, Cleft palate, Hypocalcemia, deleted chromosome 22. Furthermore, new phenotypes have been recently recognized, most of them belonging to the psychiatric spectrum. Descriptive studies of large samples of children with 22q11 deletion, conducted, both in the United States and european countries, have shown the following pattern of associated symptoms:--abnormal face (100%), which expression varies with age, and can be discrete;--cardiac abnormalities (84%), including cardiac malformations of conotroncal types;--mouth abnormalities (49%), including cleft palate (14%), and velar dysfunction (20%);--urinary tract abnormalities (36%), including ureteric reflux, lung dysplasia;--transitory hypocalcemia (60%) mostly during infancy, and due to transitory hypoparathyroid dysfunction;--seizures (21%), which are usually a consequence of hypocalcemia;--immunodeficiency (1%), which worsens the prognosis. Deletion of chromosome 22q11 has been also associated with various psychiatric phenotypes, which can be classified into two groups, developmental abnormalities and psychiatric conditions. The great majority of patients with the deletion exhibit impairment of language and motor development, mild mental retardation, persistent coordination deficits, and poor academic performance. The deletion of chromosome 22q11 is also associated with high frequency of behavioral disorder with attention deficit during childhood, and with high frequency of psychotic disorder (bipolar disorder, and schizophrenia) during adolescence and young adulthood. The link between the 22q11 deletion and schizophrenia has been also supported by recent studies showing that the rate of 22q11 deletion in adults with schizophrenia (2%) is higher than it is in the general population. The rate may even be higher (6%) in subjects with childhood onset schizophrenia. The present work reviews the psychiatric literature associated with 22q11 deletion. We also report a case of 22q11 deletion in a 17-year-old girl that was initially diagnosed as paranoid schizophrenia. We will discuss the diagnostic, prognostic, and therapeutic consequences that such a genetic diagnosis implies. In the case reported here, transitory hypocalcemia induced: 1) dystonic symptoms that was believed to be catatonic symptoms or neuroleptic secondary effects, by clinicians; 2) a poor response to neuroleptic medication.
 ...
PMID:[Microdeletion 22q11: apropos of case of schizophrenia in an adolescent]. 1129 38

DiGeorge syndrome (DGS) is a developmental field defect of the third and fourth pharyngeal pouches that are associated with congenital heart defects, hypoparathyroidism, cell-mediated immunodeficiency, velopharyngeal insufficiency, and craniofacial anomalities. Approximately 90% of patients exhibit monosomy in the 22q11 region. In order to isolate the critical gene responsible for DGS, the cDNA libraries were screened with a probe containing the ADU balanced translocation break point, that is a locus reported in one patient (ADU) caused by a balanced translocation between chromosomes 22 and 2. Out of 10(6) clones, three independent overlapping clones were isolated, which were assumed to have originated from a single transcript, DGCR7. This transcript contained a 175-aa long open reading frame (ORF), encoding an acidic (pI = 5.81) and a proline-rich peptide, which are often found in the activation domain of several transcription factors. Also, it was predicted to be a nuclear protein. Northern hybridization detected an approx 1.9 kb transcript in all fetal and adult tissues tested, with strong expression in the fetal liver and kidney. In the case of adult tissues, strong expression was also detected in areas such as the heart, skeletal muscle, liver, and kidney.
 ...
PMID:Isolation of novel cDNA encompassing the ADU balanced translocation break point in the DiGeorge critical region. 1143 9

Extremely preterm neonates and neonates with predisposing conditions such as congenital or acquired immunodeficiency are at high risk for systemic fungal infection. Abscess formation in the brain is a severe complication that occurs in 70% of neonates with systemic fungal infection. Cerebral sonography can be used to diagnose abscesses in the brain in these patients. We report 2 sonographic presentations of fungal brain abscesses in neonates confirmed by postmortem histopathologic examination. The first patient, an extremely preterm neonate of 23 weeks' gestation with a systemic Candida albicans infection, had multiple small, round, hypoechoic lesions with echogenic rims in both brain hemispheres. The second patient, a term neonate with disseminated aspergillosis and DiGeorge syndrome, had a few large echogenic areas in the right periventricular region. Brain imaging should be considered in the diagnostic workup in neonates with suspected systemic fungal infection. Cerebral involvement can be diagnosed at the bedside with cerebral sonography.
 ...
PMID:Fungal brain abscesses in neonates: Sonographic appearances and corresponding histopathologic findings. 1157 6

DiGeorge syndrome is characterized by conotruncal cardiac defects, hypocalcemia, and a hypoplastic thymus. Many, but not all, patients have a heterozygous deletion of chromosome 22q11.2. In its most severe form, it represents a devastating syndrome with high mortality. Patients with severe immunodeficiency are candidates for a thymic transplant or a fully matched bone marrow transplant. Fortunately, the majority of patients with either DiGeorge syndrome or chromosome 22q11.2 deletion syndrome have a mild to moderate immunodeficiency. These patients may develop recurrent infections or autoimmune disease.
 ...
PMID:DiGeorge syndrome/chromosome 22q11.2 deletion syndrome. 1189 70

In order to study the functions of simian immunodeficiency virus (SIV) Nef in vivo in a small-animal model, we constructed transgenic (Tg) mice expressing the SIV(mac)239 nef gene in the natural target cells of the virus under the control of the human CD4 gene promoter (CD4C). These CD4C/SHIV-nef(SIV) Tg mice develop a severe AIDS-like disease, with manifestations including premature death, failure to thrive or weight loss, wasting, thymic atrophy, an especially low number of peripheral CD8+ T cells as well as a low number of peripheral CD4+ T cells, diarrhea, splenomegaly, and kidney (interstitial nephritis, segmental glomerulosclerosis), lung (lymphocytic interstitial pneumonitis), and heart disease. In addition, these Tg mice fail to mount a class-switched antibody response after immunization with ovalbumin, they produce anti-DNA autoantibodies, and some of them develop Pneumocystis carinii lung infections. All these results suggest a generalized Nef-induced immunodeficiency. The low numbers of peripheral CD8+ and CD4+ T cells are likely to reflect a thymic defect and may be similar to the DiGeorge-like "thymic defect" immunophenotype described for a subgroup of human immunodeficiency virus type 1-infected children. Therefore, it appears that SIV Nef alone expressed in mice, in appropriate cell types and at sufficient levels, can elicit many of the phenotypes of simian and human AIDS. These Tg mice should be instrumental in studying the pathogenesis of SIV Nef-induced phenotypes.
 ...
PMID:Expression of simian immunodeficiency virus nef in immune cells of transgenic mice leads to a severe AIDS-like disease. 1190 38

Bruton's XLA and DiGeorge syndrome patients show that two basic immune systems are distinct from each other in humans - thymus-dependent cell-mediated immunodeficiencies vs. antibody-based immunodeficiencies. The appendix-sacculus lymphoid organ of rabbits, like the bursa of Fabricius, represents a central lymphoid organ. Chronic granulomatous disease of childhood (CGD) revealed that phagocytosis killing of catalase-positive microorganisms employ oxidative burst. Bone marrow transplantation (BMT) proved life saving in severe combined immunodeficiency (SCID). The first BMT cured XSCID and the second BMT cured a complicating aplastic anemia launching BMT as a treatment of many diseases. Now 75 fatal diseases have been cured by myeloablative BMT. BMT also cured experimental autoimmune diseases. BMT alone did not cure lupus with polyarthritis in MRL/lpr mice or polyarthritis in NZB/KN mice, but BMT plus bone (stromal cell) transplants cured these diseases. Autoimmune diseases and lethal glomerulonephritis were prevented or cured in BXSB mice by mixed allogeneic plus syngeneic BMT. X-linked Hyper IgM syndrome (XHIM) was also cured by BMT from a 2-year-old MHC-matched sibling donor. Nonmyeloablative BMT plus mesenchymal stem cells (stromal cells) was effective treatment for a form of collagen-vascular disease and also a lethal form of hypophosphatasia. Mannan-binding lectin, an opsonin that activates the complement system when mutated and at low levels in blood, opens a door to frequent infections throughout childhood and adult life. This new immunodeficiency is based on genetic mutations that involve a native defense system.
 ...
PMID:Cellular immunology in a historical perspective. 1219 Sep 28

The most common immunodeficiency in DiGeorge sequence patients is defects in T-cell production due to insufficient thymic tissue. However, because T-lymphocytes are important in regulating antibody responses, DiGeorge sequence is no longer regarded as a pure deficiency of cellular immunity but also a form of variable-combined immunodeficiency. Here we presented a 4-month-old male infant with characteristic facial dysmorphism, thymus dysplasia, tetralogy of Fallot, and documented deletion of chromosome 22q11.2 who had decrease B-lymphocyte numbers and hypogammaglobulinemia. The mitogen responses of T-lymphocytes function were normal with adequate number of CD4+ lymphocytes. This case report highlights the importance of evaluating not only the cellular but also the humoral immune function in patients with DiGeorge sequence.
 ...
PMID:DiGeorge sequence with hypogammaglobulinemia: a case report. 1238 Jul 93

We evaluated the T-cell repertoire and the thymic output in two infants, one with Omenn Syndrome (OS) and another with complete DiGeorge Syndrome (DGS), who developed generalized dermatitis. The patients shared common T-cell abnormalities, as demonstrated by the low response to mitogenic stimulation, by an unusual usage of specific T-cell receptor (TCR) segments, and by a reduction of TCR diversity in both alpha/beta and gamma/delta populations. Furthermore, they both showed an impaired thymic function, as assessed by the low number of TCR recombination excision circles, which are formed from excised DNA during the rearrangement of TCR genes. These data indicated that generalized erythrodermia may be present in different forms of T-cell immunodeficiency and may reflect intrinsic defects in either V(D)J recombination or in thymic development, leading to the peripheral expansion of T-cell clonotypes, that bear peculiar TCR chains.
 ...
PMID:Impaired thymic output and restricted T-cell repertoire in two infants with immunodeficiency and early-onset generalized dermatitis. 1260 Jul 51

Chromosome 22q11.2 deletion (del22q11.2) syndrome (DiGeorge syndrome/velocardiofacial syndrome) is a common syndrome typically consisting of congenital heart disease, hypoparathyroidism, developmental delay and immunodeficiency. Although a broad range of immunologic defects have been described in these patients, limited information is currently available on the diversity of the T-cell receptor (TCR) variable beta (BV) chain repertoire. The TCRBV repertoires of nine patients with del22q11.2 syndrome were determined by flow cytometry, fragment size analysis of the third complementarity determining region (CDR3 spectratyping) and sequencing of V(D)J regions. The rate of thymic output and the phenotype and function of peripheral T cells were also studied. Expanded TCRBV families were detected by flow cytometry in both CD4+ and CD8+ T cells. A decreased diversity of TCR repertoires was also demonstrated by CDR3 spectratyping, showing altered CDR3 profiles in the majority of TCRBV families investigated. The oligoclonal nature of abnormal peaks detected by CDR3 spectratyping was confirmed by the sequence analysis of the V(D)J regions. Thymic output, evaluated by measuring TCR rearrangement excision circles (TRECs), was significantly decreased in comparison with age-matched controls. Finally, a significant up-regulation in the percentage, but not in the absolute count, of activated CD4+ T cells (CD95+, CCR5+, HLA-DR+), IFN-gamma - and IL-2-expressing T cells was detected. These findings suggest that the diversity of CD4 and CD8 TCRBV repertoires is decreased in patients with del22q11.2 syndrome, possibly as a result of either impaired thymic function and/or increased T-cell activation.
 ...
PMID:Biased T-cell receptor repertoires in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). 1269 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>