Amsterdam: Elsevier/North Holland, p 499, 1980. MHC-II deficiency patients in complementation groups B, C, and group D exhibit the characteristic deficiency in RFX binding activity, the absence of DNAse I hypersensitive sites, and a bare promoter (47,48,60,80). IFN-α treatment trials worsened the lesions. Emery P, Durand B, Mach B, Reith W. RFX proteins, a novel family of DNA binding proteins conserved in the eukaryotic kingdom. Class II transactivator (CIITA) is sufficient for the inducible expression of major histocompatibility complex class II genes. As for other combined immunodeficiency disorders, allogeneic BMT is considered the treatment of choice for MHC-II deficiency. Steimle V, Durand B, Barras E, Zufferey M, Hadam MR, Mach B, Reith W. A novel DNA binding regulatory factor is mutated in primary MHC class II deficiency (bare lymphocyte syndrome). Recent progress in immunobiology and genetics has identified with increasing precision the causes of many primary immunodeficiencies; diagnosis and therapy, as a result, can be more specific and effective (26,87). J Immunol 146: 2310–2315, 1991. Antibody responses to immunizations and infections by microbial agents are generally absent or strongly reduced. Few children reach puberty; the majority die between the ages of 6 months and 5 years (Table 1). 0000006840 00000 n In addition, the protein CIITA is essential for the MHC-II gene expression. 0000006684 00000 n Immunol Today 16: 539–546, 1995. [email protected]. 32. Griscelli C, Durandy A, Virelizier JL, Hors J, Lepage V, Colombani J. 24. In such cells, the expression of CIITA, and thus of MHC-II genes, can generally be induced by stimulation with IFN-γ(11,99). 0000043816 00000 n As expected for a rare disease, there is a high incidence of consanguinity in the affected families (56). Peijnenburg A, Godthelp B, van Boxel-Dezaire A, van den Elsen PJ. 0000005105 00000 n The evaluation of T-lymphocyte subpopulations reveals a normal or increased CD4.
Seidl C, Saraiya C, Osterweil Z, Fu YP, Lee JS. In: Seligman M, Hitzig WH, eds. Masternak K, Barras E, Zufferey M, Conrad B, Corthals G, Aebersold R, Sanchez JC, Hochstrasser DF, Mach B, Reith W. A gene encoding a novel RFX-associated transactivator is mutated in the majority of MHC class II deficiency patients. Gene therapy before bone marrow transplantation, which remains until now the only recognized curative therapy, to reduce early infection and thus to increase success of the transplantation performed later. The RFXANK gene has also been called RFX-B to indicate that it is mutated in complementation group B (69). 72. The class II transactivator (CIITA) is mutated in CG A, whereas the 3 subunits of the regulatory factor X (RFX), namely RFX containing ankyrin repeats (RFXANK), the fifth member of the RFX family (RFX5), and RFX-associated protein (RFXAP), are defective in CGs B, C, and D, respectively. RFX5 belongs to a novel family of related DNA-binding proteins; other members of this family are not involved in the control of the MHC-II gene expression (24).
Failure to thrive, thrush and hypogammaglobulinemia in 6-month-old child.
0000044994 00000 n Molecular analysis of an MHC class II deficiency patient reveals a novel mutation in the RFX5 gene. A considerable amount of effort has been devoted to the identification and isolation of DNA-binding proteins that control transcription of MHC-II genes by interacting with the S, X, X2, and Y boxes.
0000006449 00000 n
0000006607 00000 n 97. Mol Cell Biol 19: 431–40, 1999. Because these molecules have a pivotal role in the control of various immune responses, their absence results in severely impaired cellular and humoral immune responses, leading to significant susceptibility to severe infections and, frequently, death in early childhood. MCH class II molecules mediate several key functions in the adaptive immune system, directing the development, activation, and homeostasis of CD4. Haemophilus and Proteus species have also been isolated. J Exp Med 181: 1411–1423, 1995. Bontron S, Steimle V, Ucla C, Mach B.
0000020807 00000 n 86. MHC class II deficiency: Report of a novel mutation and special review The MHC II deficiency is a rare autosomal recessive primary immunodeficiency syndrome with increased susceptibility to respiratory and gastrointestinal infections, failure to thrive and early mortality. 85.
Two of the promoters direct constitutive expression in professional antigen presenting cells. Specific complex formation between the type II bare lymphocyte syndrome-associated transactivators CIITA and RFX5. Moreno CS, Emery P, West JE, Durand B, Reith W, Mach B, Boss JM. Immunity 1: 3–6, 1994.
105. van Huijsduijnen RH, Li XY, Black D, Matthes H, Benoist C, Mathis D. Co-evolution from yeast to mouse: cDNA cloning of the two NF-Y (CP-1/CBF) subunits. 104. 0000012809 00000 n However, in vivo footprint experiments have demonstrated that these patients exhibit an unusual promoter occupancy phenotype. 53. HLA homozygosity in suspected indexes suggests TAP or tapasin deficiency because both molecules are located within the MHC locus on chromosome 6. 2014. Some error has occurred while processing your request. Muhlethaler-Mottet A, Di Berardino W, Otten LA, Mach B. Activation of the MHC class II transactivator CIITA by interferon-gamma requires cooperative interaction between Stat1 and USF-1. Recurrent bronchopulmonary infections have been observed in all patients.
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0000013817 00000 n Failure to thrive, diarrhea, liver/biliary tract disease Autoimmune cytopenias, Normal responses on mitogen stimulation. 0000004920 00000 n Umbilical vein puncture and analysis of MHC class II expression on fetal leukocytes is an alternative when genetic background is unknown. The disease is due to defects in transacting regulatory factors required for expression of MHC-II genes. Among the primary immunodeficiencies, MHC class II deficiency (MHC-II deficiency) is caused by the absence of MHC-II expression on the cell surface. 11. Complementation of a cell line from a patient (SJO) in complementation group C led to the isolation of RFX5, the 75 kD subunit of RFX (97). Published by Wolters Kluwer Health, Inc. Science 252: 709–712, 1991. Herman A, Kappler JW, Marrack P, Pullen AM. Autoimmune manifestations were observed in approximately 20% of patients, such as autoimmune cytopenias, anemia, neutropenia, and/or thrombocytopenia (. The N-terminal extremity is rich in acidic amino acids, and it has also been reported to resemble a PEST (proline/glutamic acid/serine/threonine) domain (69).
68. Introduction of the wildtype CIITA, RFX5, RFXAP, and RFXANK genes into hematopoietic stem cells of patients in complementation groups A, B, C, and D, respectively, would represent a logical therapeutic strategy. Blood 85: 580–587, 1995. 0000015339 00000 n Among them, MHC class II deficiency (MHC-II deficiency) is caused by the absence of MHC-II expression on the cell surface. MHC class I and II deficiencies are extremely rare PIDs, both of which share defective antigen presentation to CD8, Accepted: