1/29. Viral infections in interferon-gamma receptor deficiency.interferon-gamma receptor deficiency is a recently described immunodeficiency that is associated with onset of severe mycobacterial infections in childhood. We describe the occurrence of symptomatic and often severe viral infections in 4 patients with interferon-gamma receptor deficiency and mycobacterial disease. The viral pathogens included herpes viruses, parainfluenza virus type 3, and respiratory syncytial virus. We conclude that patients with interferon-gamma receptor deficiency and mycobacterial disease have increased susceptibility to some viral pathogens.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
2/29. Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation.A 5-week-old male infant presented with severe bacterial infections and poor wound healing, suggesting a neutrophil defect. neutrophils from this patient exhibited decreased chemotaxis, polarization, azurophilic granule secretion, and superoxide anion (O(2)(-)) production but had normal expression and up-regulation of CD11b. Rac2, which constitutes >96% of the Rac in neutrophils, is a member of the Rho family of GTPases that regulates the actin cytoskeleton and O(2)(-) production. Western blot analysis of lysates from patient neutrophils demonstrated decreased levels of Rac2 protein. Addition of recombinant Rac to extracts of the patient neutrophils reconstituted O(2)(-) production in an in vitro assay system. Molecular analysis identified a point mutation in one allele of the Rac2 gene resulting in the substitution of Asp57 by an Asn (Rac2(D57N)). Asp57 is invariant in all defined gtp-binding proteins. Rac2(D57N) binds GDP but not GTP and inhibits oxidase activation and O(2)(-) production in vitro. These data represent the description of an inhibitory mutation in a member of the Rho family of GTPases associated with a human immunodeficiency syndrome.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
3/29. In a novel form of IFN-gamma receptor 1 deficiency, cell surface receptors fail to bind IFN-gamma.Complete IFN-gamma receptor ligand-binding chain (IFNgammaR1) deficiency is a life-threatening autosomal recessive immune disorder. Affected children invariably die of mycobacterial infection, unless bone marrow transplantation is undertaken. Pathogenic IFNGR1 mutations identified to date include nonsense and splice mutations and frameshift deletions and insertions. All result in a premature stop codon upstream from the segment encoding the transmembrane domain, precluding cell surface expression of the receptors. We report herein two sporadic and two familial cases of a novel form of complete IFNgammaR1 deficiency in which normal numbers of receptors are detected at the cell surface. Two in-frame deletions and two missense IFNGR1 mutations were identified in the segment encoding the extracellular ligand-binding domain of the receptor. Eight independent IFNgammaR1-specific mAb's, including seven blocking antibodies, gave recognition patterns that differed between patients, suggesting that different epitopes were altered by the mutations. No specific binding of (125)I-IFN-gamma to cells was observed in any patient, however, and the cells failed to respond to IFN-gamma. The mutations therefore cause complete IFNgammaR1 deficiency by disrupting the IFN-gamma-binding site without affecting surface expression. The detection of surface IFNgammaR1 molecules by specific antibodies, including blocking antibodies, does not exclude a diagnosis of complete IFNgammaR1 deficiency.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
4/29. Familial CD8 deficiency due to a mutation in the CD8 alpha gene.CD8 glycoproteins play an important role in both the maturation and function of MHC class I-restricted T lymphocytes. A 25-year-old man, from a consanguineous family, with recurrent bacterial infections and total absence of CD8( ) cells, was studied. Ab deficiencies and ZAP-70 and TAP defects were ruled out. A missense mutation (gly90-->ser) in both alleles of the immunoglobulin domain of the CD8 alpha gene was shown to correlate with the absence of CD8 expression found in the patient and two sisters. Conversely, high percentages of CD4(-)CD8(-)TCR alpha beta( ) T cells were found in the three siblings. A novel autosomal recessive immunologic defect characterized by absence of CD8( ) cells is described. These findings may help to further understanding of the role of CD8 molecules in human immune response.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
5/29. A novel case of immunodeficiency, centromeric instability, and facial anomalies (the ICF syndrome): immunologic and cytogenetic studies.The immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is characterized by hypogammaglobulinemia and recurrent bacterial infections. Here we report a novel case of ICF syndrome with hypogammaglobulinemia and an inverted CD4/CD8 ratio. Cytogenetically abnormal cells,that were identified in both CD4 and CD4- peripheral blood lymphocytes, retained their ability to proliferate in vitro following polyclonal stimulation. A primitive defect of B-cell differentiation was detected.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
6/29. Correction of complete interferon-gamma receptor 1 deficiency by bone marrow transplantation.Complete interferon-gamma receptor 1 (IFNgammaR1) deficiency is a primary immunodeficiency disease characterized by high susceptibility to recurrent, severe mycobacterial and other intracellular infections. We here report the first successful treatment of the disorder by bone marrow transplantation (BMT). The 8-year-old girl had suffered from recurrent mycobacterial infections in the past and had developed liver cirrhosis with portal hypertension. For conditioning, fractionated total body irradiation (TBI) was used in combination with cyclophosphamide and antithymocyte globulin (ATG). The patient received red cell-depleted bone marrow from her HLA-identical sister. The transplantation course was uneventful and 4 years later, the child remains in excellent clinical condition and free of mycobacterial infections. She has stable mixed lymphohematopoietic chimerism after repeat T-cell transfusions. Liver disease has not further deteriorated. This experience shows that correction of IFNgammaR1 deficiency is possible by BMT and complications of the disease can be controlled.- - - - - - - - - - ranking = 2keywords = bacterial infection (Clic here for more details about this article) |
7/29. Identification of two molecular defects in a child with leukocyte adherence deficiency.Children with leukocyte adherence deficiency (LAD), or leukocyte cell adhesion molecule deficiency, experience recurrent, life-threatening bacterial infections related to severe deficiency in surface expression of the leukocyte integrin molecules. The leukocyte integrins consist of a common CD18 (beta) subunit and individual, noncovalently associated alpha subunits designated CD11a, CD11b, and CD11c. Defects in the CD18 subunit prevent surface expression of the CD11/CD18 complexes in children with this disease. We investigated the molecular basis of the disease in a child with the severe deficiency form of LAD and identified two molecular defects in the CD18 subunit. The first defect is a single-base pair C T transposition resulting in an amino acid substitution of a leucine for a proline at amino acid 178. This amino acid substitution is located in a region that is highly conserved among the integrin beta subunits and where two previous defects have been located in LAD. The second mutation involves a deletion of 220 base pairs in the cDNA coding for a portion of the extracellular domain and results in a frameshift into a premature stop codon. The deleted region corresponds to a single exon in the CD18 gene. Identification of these two molecular defects in a single child with this disease indicates the compound heterozygous nature of the disorder in this child and identifies regions of the CD18 subunit that may be important for CD11/CD18 heterodimer formation and surface expression.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
8/29. Hyper-IgM syndrome: a case report.Hyperimmunoglobulin M syndrome is a rare primary immunodeficiency disorder. We report a case of a 6-month-old boy who suffered from developmental delays, frequent respiratory tract infection, and unusual fungal and bacterial infection. X-linked hyperimmunoglobulin M syndrome was ultimately diagnosed with decreasing immunoglobulin-G, A, and E (immunoglobulin g = 51.3 mg/dL, immunoglobulin a = 8.32 mg/dL, immunoglobulin e <17.5 mg/dL), elevating immunoglobulin m (immunoglobulin m = 140 mg/dL), and decreasing T-cell expression of the cd40 ligand over flow cytometry. Seizure episodes and hypotonia developed with greater signal intensity at the putamen in a brain magnetic resonance imaging, which is compatible with hypoxic ischemic encephalopathy. This is the youngest proven case of hyper-IgM syndrome in taiwan ever reported.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
9/29. HHV-8-associated Kaposi sarcoma in a child with IFNgammaR1 deficiency.OBJECTIVES: Mediterranean classic Kaposi sarcoma (KS) of childhood is rare and unexplained. Our objective is to describe the case of a child with complete IFNgammaR1 deficiency and severe mycobacterial disease in whom Kaposi sarcoma (KS) developed. RESULTS: Disseminated mycobacterial infection began at the age of 5 months, and at 11 years of age the child had disseminated KS lesions. The histologic appearance of these lesions was typical, with endothelial and spindle cell proliferation. Human herpesvirus-8 (HHV-8)-associated antigens were detected in situ by immunohistochemistry. HHV-8 dna of K1 molecular subtype A was amplified from tissue lesions, and HHV-8-specific antibodies were detected in the patient's serum. The child died at 12 years of age of disseminated mycobacterial disease and KS. CONCLUSIONS: This is the first identification of a well-defined primary immunodeficiency in a child with KS. Inherited disorders of IFN-gamma-mediated immunity and severe mycobacterial disease may predispose HHV-8-infected children to KS.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
10/29. Interleukin receptor-associated kinase (IRAK-4) deficiency associated with bacterial infections and failure to sustain antibody responses.We previously described a girl with recurrent episodes of pneumococcal pneumonia with septicemia and other infections,(1) found to have interleukin-1 receptor-associated kinase 4 deficiency (IRAK-4) deficiency.(2) In this report, we show that our patient is unable to sustain antibody responses either to polysaccharide or protein antigens or to a neoantigen-bacteriophage.- - - - - - - - - - ranking = 4keywords = bacterial infection (Clic here for more details about this article) |
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