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)

DBA/2Ha mice have an X-chromosome-linked immunodeficiency and lack the receptor to a TRF (T cell replacing factor) on a subpopulation of B cells. Their immunodeficiency is considered to resemble that of CBA/N, another X-chromosome-linked immunodeficiency. To facilitate direct comparisons of the two immunodeficiencies and to study the in vivo manifestations of DBA/2Ha immunodeficiency, we measured phenotypes and functions of B cells of DBA/2Ha mice. We found that the expression of sIgM among B cells is normal in DBA/2Ha mice, heterozygous females equally express both affected and normal B cell subpopulations, and DBA/2Ha mice respond well to a TI-2 antigen (TNP-Ficoll) and a polyclonal activator (LPS). Unlike CBA/N, DBA/2Ha mice demonstrate very little in vivo immunodeficiencies.
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PMID:Study of the DBA/2Ha immunodeficiency: X-chromosome mosaicism and in vivo immunoresponses. 349 86

CBA/N and CBA/CaHN have a significantly longer latent period than other inbred mouse strains between infection with Moloney murine leukemia virus and the appearance of T cell lymphoma. The genetic characteristics of this resistance have been analyzed in the F1 hybrids of CBA/N and CBA/CaHN with BALB H-2 congenic strains. Sexual phenotype and H-2 haplotype significantly influenced survival in the F1 hybrids of CBA/CaHN with BALB. In the F1 with BALB/cJ and BALB/cAnN (both H-2d), the males survived significantly longer than the females; but in the F1 with BALB.K (H-2k) and BALB.B (H-2b), the survival of males and females was the same. Survival was not prolonged by the recessive X-linked immunodeficiency gene xid or other genes on the CBA/N X-chromosome, because the (CBA/N X BALB/c)F1 male and the reciprocal (BALB/c X CBA/N)F1 male, which does not carry the CBA X-chromosome, were equally resistant. H-2 haplotype did not influence survival among the BALB H-2 congenics, and sex had little effect on the resistance of the CBA and BALB parents. These results demonstrate that a sex-dependent gene linked to H-2 significantly influences the expression of CBA genes for lymphoma resistance in the F1 hybrid with BALB.
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PMID:Sex and H-2 haplotype control the resistance of CBA-BALB hybrids to the induction of T cell lymphoma by Moloney leukemia virus. 633 61

The immunocapacity of a 28-year-old mentally retarded proband and her clinically normal mother and sister, all having a deletion of the short arm of one of the X-chromosomes [46, X, del (X) (pter to 22: :p11 to qter)], was evaluated. The concentrations of immunoglobulin IgA (0 . 4 g/l), IgG (4 . 4 g/l) and IgM (0 . 2 g/l) were low in the proband. The serum IgA (0 . 9 g/l) concentration of her mother was also at the lower normal limit. The serum concentration of complement component C4 was low both in the proband (0 . 17g/l) and in her mother (0 . 18 g/l). Phagocytosis and killing of bacteria by granulocytes were normal in all of them. However, the chemotactic response of granulocytes was at the lower normal level in the patient. The in vitro responses of peripheral blood lymphocytes to the polyclonal T-clonal mitogens, PHA and Con A, were about half normal in the patient and were also decreased in her mother. The response was also decreased against PWM, to about one-sixth of the normal value in the patient and to one-half in her mother. The Con A response was decreased in the sister, while her PHA and PWM responses were normal. In contrast to these findings, the responses against the antigen-specific stimulators, PPD and oidiomycin, were normal in all subjects. Natural killer cell activity against the K-562 cell line was decreased in the patient but normal in her mother and sister. The number of B cells was at the normal limit in all subjects. The amount of E rosette-forming T lymphocytes was normal but the amount of ANAE-positive cells was decreased, especially in the proband (31%). Our results describe a new human immunodeficiency state, probably associated with X-chromosome deletion. We suggest that the short arm of the X-chromosome exerts its effect on regulatory T cells. Whether the humoral defect is connected with suppressor T cells remains to be established.
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PMID:Immunodeficiency associated with a deletion in the short arm of the X-chromosome. 730 43

The Wiskott-Aldrich syndrome (WAS) is an X-linked (Xp11.22) recessive immunodeficiency syndrome characterized by susceptibility to opportunistic and pyogenic infections, thrombocytopenia, and eczema. Previous studies of obligate carriers of WAS documented that nonrandom inactivation of the X chromosome carrying the defective gene is observed in all peripheral blood cells. The existence of both abnormal platelets and lymphocytes is consistent with a defect that affects early hematopoietic precursors. We isolated CD34+ hematopoietic progenitor cells collected from obligate carriers of WAS by apheresis and used polymerase chain reaction analysis of a polymorphic variable number of repeats (VNTR) within the X-linked androgen receptor to document nonrandom inactivation. These data show that nonrandom inactivation of the X-chromosome in WAS-obligate carriers occurs early during hematopoietic differentiation.
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PMID:Nonrandom inactivation of the X chromosome in early lineage hematopoietic cells in carriers of Wiskott-Aldrich syndrome. 753 15

Wiskott-Aldrich syndrome (WAS) is a fully penetrant X-linked recessive disorder characterized by immunodeficiency, thrombocytopenia, and severe eczema. WAS is a life-threatening disease, with a poor quality of life and high mortality rate in childhood. The gene responsible for the disease has been localized to the proximal short arm of the X-chromosome and recently isolated through positional cloning and named WAS protein (WASP). We have characterized 17 WAS families. We have developed a rapid, nonradioactive screening protocol for identifying WASP gene alterations in genomic DNA. Our method allows simultaneous evaluation of single strand confirmation polymorphism and heteroduplex formation. We have identified 15 novel mutations that involve single basepair changes, or small insertions or deletions, all of which result in premature stop cordon, frame shift with secondary premature stop codon, or splice site defect. These studies document the considerable heterogeneity of the location of mutations in the WASP gene causing full-blown WAS and show the efficiency and rapidity of a screening approach for mutation identification in WAS that will be useful for carrier detection and prenatal diagnosis.
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PMID:High prevalence of nonsense, frame shift, and splice-site mutations in 16 patients with full-blown Wiskott-Aldrich syndrome. 757 29

The Wiskott-Aldrich syndrome (WAS) is an X-chromosome-linked recessive disease characterized by eczema, thrombocytopenia, and immunodeficiency. The disease gene has been localized to the proximal short arm of the X chromosome and recently isolated through positional cloning. The function of the encoded protein remains undetermined. In this study we have characterized mutations in 12 unrelated patients to confirm the identity of the disease gene. We have also revised the coding sequence and genomic structure for the WAS gene. To analyze further the transmittance of the disease gene, we have characterized a polymorphic microsatellite at the DXS6940 locus within 30 kb of the gene and demonstrate the inheritance of the affected alleles in families with a history of WAS.
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PMID:Identification of mutations in the Wiskott-Aldrich syndrome gene and characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent to the disease gene. 775 69

Clinical and immunologic features of a recently recognized X-linked combined immunodeficiency disease (XCID) suggested that XCID and X-linked severe combined immunodeficiency (XSCID) might arise from different genetic defects. The recent discovery of mutations in the common gamma chain (gamma c) gene, a constituent of several cytokine receptors, in XSCID provided an opportunity to test directly whether a previously unrecognized mutation in this same gene was responsible for XCID. The status of X chromosome inactivation in blood leukocytes from obligate carriers of XCID was determined from the polymorphic, short tandem repeats (CAG), in the androgen receptor gene, which also contains a methylation-sensitive HpaII site. As in XSCID, X-chromosome inactivation in obligate carriers of XCID was nonrandom in T and B lymphocytes. In addition, X chromosome inactivation in PMNs was variable. Findings from this analysis prompted sequencing of the gamma c gene in this pedigree. A missense mutation in the region coding for the cytoplasmic portion of the gamma c gene was found in three affected males but not in a normal brother. Therefore, this point mutation in the gamma c gene leads to a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID.
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PMID:Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency. 788 65

CD40 ligand (CD40L) on activated T cells plays a crucial role for Ig heavy-chain class switching and the mutation of the gene for this ligand in the X-chromosome causes immunodeficiency with hyper-IgM (X-HIM). We isolated and characterized the human genomic clone for CD40 L to obtain information about the transcriptional regulatory regions of the gene and to develop a molecular diagnostic method for X-HIM patients. The genomic DNA isolated was over 12 kb long containing 5 exons that cover full sequence of mRNA for the ligand. DNA motif analysis based on transcription factor database revealed the presence of a GATA 1 box at around -265 bp. The typical TATA box, CAT site or GC rich region was not found in the 5' flanking region. However, two possible TATA like sequences were found at around -27 and -136 bp. Using the oligonucleotide primers corresponding to the introns, we performed a PCR-SSCP analysis of each exon from a patient with X-HIM syndrome and detected abnormality in exon 5. When sequenced, dinucleotide deletion in this exon was found in the patient and in one X allele of his mother as the only different sequence from that of the control gene. This procedure is simple and could be used for diagnosis of the X-HIM syndrome.
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PMID:Structural organization of the gene for CD40 ligand: molecular analysis for diagnosis of X-linked hyper-IgM syndrome. 799 97

Bruton's tyrosine kinase (Btk) is a cytoplasmic protein kinase that is defective in X-linked agammaglobulinaemia in man and in X-linked immunodeficiency in the mouse. There is controversy regarding the stages of B cell development that are dependent on Btk function. To determine the point in B cell differentiation at which defects in Btk become apparent, we generated a mouse model by inactivating the Btk gene through an in-frame insertion of a lacZ reporter by homologous recombination in embryonic stem cells. The phenomenon of X-chromosome inactivation in Btk+/- heterozygous female mice enabled us to evaluate the competition between B cell progenitors expressing wild-type Btk and those expressing the Btk-/lacZ allele in each successive step of development. Although Btk was already expressed in pro-B cells, the first selective disadvantage only became apparent at the transition from small pre-B cells to immature B cells in the bone marrow. A second differentiation arrest was found during the maturation from IgD(low)IgM(high) to IgD(high)IgM(low) stages in the periphery. Our results show that Btk expression is essential at two distinct differentiation steps, both past the pre-B cell stage.
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PMID:Inactivation of Btk by insertion of lacZ reveals defects in B cell development only past the pre-B cell stage. 889 Jan 60

The X-linked immunodeficiency (Xid) in CBA/N mice serves as a model for the X-linked agammaglobulinemia (XLA) syndrome in man. X-chromosome inactivation in F1 heterozygotes derived from CBA/N (Xxid/Xxid) and B6.Pgk-1a (X+/Y) was investigated by monitoring the methylation status of the individual Pgk-1 alleles, Pgk-1b and Pgk-1a, respectively, using a novel Tth111I RFLP. Results indicate that in circulating B lymphocytes of female heterozygotes, only the X chromosomes carrying the normal alleles (X+) are active (nonrandom inactivation of the X chromosome), whereas in non-B cells both the X chromosomes (X+ and Xxid) are active (random inactivation of the X chromosome). These results were further confirmed by direct evaluation of transcription of the Btk gene, the gene mutated both in Xid and in XLA.
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PMID:A novel Tth111I restriction fragment length polymorphism (RFLP) allows tracing of X-chromosome inactivation in the (Xid) heterozygote. 893 90


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