ライフサイエンスコーパス: XLP

1 XLP is caused by mutations affecting SAP, an adaptor tha

2 XLP should always be a consideration in males with Epste

3 protein missense mutations identified in 10 XLP families.

4 rs, X-linked lymphoproliferative syndrome 2 (XLP-2) and very-early-onset inflammatory bowel disease (

5 -linked lymphoproliferative syndrome type-2 (XLP-2) is associated with deficiency in X-linked inhibit

6 males, so-called sporadic XLP (males with an XLP phenotype after EBV infection but no family history

7 These results indicate that XLP(A1)-1 and XLP(A1)-2 are functional Xenopus LPA receptors and demon

8 Healthy donor and XLP patient T cells were activated with anti-CD3/CD28 in

9 hough historically the management of EPP and XLP (collectively termed protoporphyria) centered around

10 nt between identified types of mutations and XLP patient clinical presentation, additional unidentifi

11 Consequently, XLP CD4 T cells exhibited severe defects in up-regulatio

12 D1A in X-linked lymphoproliferative disease (XLP) and the role of SH2D1A mutations and Epstein-Barr v

13 us for X-linked lymphoproliferative disease (XLP) and we found mutations in the SAP gene in three XLP

14 X-linked lymphoproliferative disease (XLP) is a congenital immunodeficiency that is characteri

15 X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency arising from SH2D1A m

16 X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency characterized by extr

17 X-linked lymphoproliferative disease (XLP) is a rare congenital immunodeficiency that leads to

18 X-linked lymphoproliferative disease (XLP) is a rare immune disorder commonly triggered by inf

19 X-linked lymphoproliferative disease (XLP) is characterized by a marked vulnerability to Epste

20 ons of X-linked lymphoproliferative disease (XLP) is progressive agammaglobulinemia, caused by the ab

21 s with X-linked lymphoproliferative disease (XLP) lack such class-switched memory B cells but are hig

22 cause X-linked lymphoproliferative disease (XLP) phenotypes.

23 s with X-linked lymphoproliferative disease (XLP), a primary immunodeficiency.

24 ciency X-linked lymphoproliferative disease (XLP), which is caused by mutations in SH2D1A, are highly

25 isease X-linked lymphoproliferative disease (XLP), which is caused by mutations in SH2D1A/SAP that en

26 s with X-linked lymphoproliferative disease (XLP), who harbored germline mutations in SH2D1A, also la

27 s with X-linked lymphoproliferative disease (XLP), who lack functional SAP, were hyperresponsive to P

28 s with X-linked lymphoproliferative disease (XLP).

29 ome of X-linked lymphoproliferative disease (XLP).

30 sorder X-linked lymphoproliferative disease (XLP).

31 Furthermore, a female XLP carrier showed completely skewed X chromosome inacti

32 virus infection per se, may be critical for XLP.

33 ubstantially refines the critical region for XLP.

34 tions in the SH2D1A gene are responsible for XLP but that there is no correlation between genotype an

35 identity of DSHP as the gene responsible for XLP, and suggest a role in the regulation of lymphocyte

36 virus saimiri-immortalized CD4 Th cells from XLP patients and normal healthy individuals were examine

37 se results demonstrate that CD4 T cells from XLP patients exhibit aberrant TCR signal transduction an

38 Twenty-two patients had XLP (9.7%; 10 male and 12 female patients), and 9 patien

39 use model recapitulate key features of human XLP and clarify SAP's critical role regulating both cell

40 e latter suggests that residual NKT cells in XLP patients might contribute to variations in dysgammag

41 In this study we estimated the deletion in XLP patient 43-004 by dual-laser flow karyotyping to inv

42 Our data explain how Ct deletions in XLP alleviate autoinhibition and increase enzyme activit

43 thogenesis of lymphoproliferative disease in XLP.

44 use of RMC-4550 restores T-cell function in XLP patient cells and a SAP(y/-) model, demonstrating re

45 Further analyses of the SAP/SH2D1A gene in XLP patients have made it clear that the development of

46 reen and analysis of mutations identified in XLP patients confirm that these extended interactions ar

47 hocyte activation, while its inactivation in XLP patients results in a selective immunodeficiency to

48 ty and mortality of primary EBV infection in XLP-affected individuals.

49 nd extracellular signal-regulated kinases in XLP CD4 T cells was transient and rapidly diminished whe

50 dentified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a s

51 P/SH2D1A, the product of the gene mutated in XLP, is a small protein that comprises a single SH2 doma

52 tudies and analyses of missense mutations in XLP patients, support the notion that SAP/SH2D1A is a na

53 and SHP-1 contributed to RICD resistance in XLP T cells.

54 he dectin-1 ligand curdlan alone resulted in XLP-2-like syndromes.

55 time the occurrence of somatic reversion in XLP.

56 ronmental factors must play a strong role in XLP disease manifestations.

57 Absence of the inhibitor SAP in XLP patients affects T/B-cell interactions induced by SL

58 pendent 2B4 receptor is sufficient to induce XLP-like aggravation of EBV disease in mice with reconst

59 Patients with X-linked lymphoproliferative (XLP) disease due to deficiency in the adaptor molecule s

60 cular basis of X-linked lymphoproliferative (XLP) disease has been attributed to mutations in the sig

61 X-linked lymphoproliferative (XLP) disease is a primary immunodeficiency caused by a d

62 most cases of X-linked lymphoproliferative (XLP) syndrome, a rare genetic disorder characterized by

63 were treated with exogenous PP-IX (mimicking XLP extrahepatic protoporphyria) or with the iron chelat

64 As most XLP symptoms are due to defective T-cell function, this

65 It is unclear which aspects of XLP disease are specific to herpesvirus infection and wh

66 ssification of XIAP deficiency as a cause of XLP may not be entirely accurate.

67 CD4 T cells of XLP patients displayed elevated levels of tyrosine phosp

68 are constitutively active in CD4 T cells of XLP patients.

69 s not per se critical for the development of XLP phenotypes.

70 Therefore, development of XLP-2 in XIAP-deficient patients could be partly due to

71 The diagnosis of XLP is still difficult given its clinical heterogeneity

72 g 2 (NOD2); however, the reported effects of XLP-2 and VEO-IBD XIAP mutations on cell death have been

73 SAP-deficient mice recapitulate features of XLP, including increased T cell activation and decreased

74 infectious agents, recapitulated features of XLP.

75 For both forms of XLP, the only curative therapy at present is allogeneic

76 after EBV infection but no family history of XLP) or in 9 patients with chronic active EBV syndrome.

77 arly in patients without a family history of XLP.

78 Infection of XLP patients with EBV invariably results in fatal mononu

79 or the expression of other manifestations of XLP, and it correlates poorly with outcome.

80 the pathways involved in the pathogenesis of XLP and other immune disorders.

81 er genes), contribute to the pathogenesis of XLP.

82 These results suggest that the phenotype of XLP may result from perturbed signaling not only through

83 ic postinfectious mononucleosis phenotype of XLP with hypogammaglobulinemia and malignant lymphoma, a

84 eceptors may cause the complex phenotypes of XLP.

85 s not known why the clinical presentation of XLP is so variable.

86 NOD2 signaling while reconciling the role of XLP-2 and VEO-IBD XIAP mutations in inflammatory cell de

87 tic value of resolvin D1 in the treatment of XLP-2 and innate immunodeficiency syndromes.

88 ated immunopathology, confirming 30 years of XLP clinical observations and indirect experimentation.

89 sible deletion in Xq25 was identified in one XLP family, 43.

90 In one XLP patient (30-011) who exhibited the characteristic po

91 patients with confirmed diagnoses of EPP or XLP from November 1, 2010, to December 6, 2015, at 6 aca

92 h clinical phenotype in patients with EPP or XLP.

93 of liver dysfunction in patients with EPP or XLP.

94 verity in a large patient cohort with EPP or XLP.

95 he frequency of EBV infectivity in the other XLP phenotypes.

96 a (EPP) or X-linked-dominant protoporphyria (XLP) cause liver damage.

97 porphyria (EPP) and X-linked protoporphyria (XLP) are rare photodermatoses presenting with variable d

98 X-linked protoporphyria (XLP) is clinically similar to EPP but results from incre

99 to gain-of-function X-linked protoporphyria (XLP).

100 Nonetheless, some XLP patients demonstrate less severe clinical manifestat

101 s were found in 25 males, so-called sporadic XLP (males with an XLP phenotype after EBV infection but

102 X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensi

103 f the X-linked lymphoproliferative syndrome (XLP) has advanced significantly in the last two years.

104 f the X-linked lymphoproliferative syndrome (XLP) has advanced significantly in the past two years.

105 X-linked lymphoproliferative syndrome (XLP) is an inherited immunodeficiency characterized by i

106 ct in X-linked lymphoproliferative syndrome (XLP) is the Src homology 2 domain-containing protein SAP

107 ed in X-linked lymphoproliferative syndrome (XLP), consists of a single SH2 domain that has been show

108 both families, these findings indicate that XLP must be considered when more than one male patient w

109 These results indicate that XLP(A1)-1 and XLP(A1)-2 are functional Xenopus LPA recep

110 Here we show that XLP patients who survive primary EBV exposure carry rela

111 consistent XIAP cell death data to show that XLP-2 and VEO-IBD XIAP mutations that exhibit a loss-of-

112 The XLP disease gene product SH2D1A (SAP) interacts via its

113 The XLP gene has been mapped to chromosome band Xq25 through

114 Analysis of 35 families from the XLP Registry revealed 28 different mutations in 34 famil

115 ed by CVID were examined for a defect in the XLP gene.

116 Of 304 symptomatic males in the XLP Registry, 38 had no evidence of EBV infection at fir

117 Initially the XLP gene was assigned to a 10-cM region in Xq25 between

118 on and facilitates the identification of the XLP gene.

119 which explains in part the complexity of the XLP phenotypes.

120 A YAC contig of 2.2 Mb spanning the XLP critical region, whose orientation on chromosome X w

121 in a male cousin of the brothers led to the XLP diagnosis.

122 we found mutations in the SAP gene in three XLP patients.

123 identify interstitial deletions in unrelated XLP patients.

124 However, compared with XLP caused by SLAM-Associated Protein deficiency (SH2D1A

125 ales with clinical syndromes consistent with XLP, predominantly EBV-HLH, had patterns of SH2D1A prote

126 bulinemia in female members of families with XLP disease.

127 e we show that T cells from individuals with XLP are specifically resistant to apoptosis mediated by

128 tory T (Treg) cell function in patients with XLP and healthy control subjects.

129 In addition, patients with XLP displayed defective peripheral B-cell tolerance, whi

130 Male patients with XLP had significantly higher ePPIX levels, on average, t

131 variability was seen in female patients with XLP owing to random X-chromosomal inactivation.

132 Treg cells in patients with XLP seem functional, but SAP-deficient T cells were resi

133 rant/transitional B cells from patients with XLP were enriched in autoreactive clones, revealing a de

134 Three of 4 patients with XLP, as confirmed by the detection of mutations in the S

135 g the phenotype and outcome of patients with XLP.

136 amed DSHP in 6 of 10 unrelated patients with XLP.

137 argeted treatment approach for patients with XLP.

138 ty of primary EBV infection in patients with XLP.

139 otential therapeutic target in patients with XLP.