ライフサイエンスコーパス: ALPS

1 ALPS insertion is severely hampered when monounsaturated

2 ALPS is a unique clinical syndrome in which in vitro abn

3 ALPS is subdivided into: 1) Type Ia, ALPS with mutant Fa

4 ALPS uses prior information about pathways in concert wi

5 ALPS was diagnosed in 47% of patients tested.

6 ALPS was identified in 9 unrelated children as manifeste

7 We surveyed a cohort of 100 ALPS patients (including 33 splenectomized) and found th

8 otic Bcl-2 family members in T cells from 12 ALPS patients and determined the in vitro sensitivity of

9 e natural history and pathophysiology of 150 ALPS-FAS patients and 63 healthy mutation-positive relat

10 Three of the 4 ALPS-U patients with normal FAS expression carried heter

11 with Fas mutations were identified in 7 of 8 ALPS kindreds.

12 Spleen sections from 9 ALPS patients revealed double-negative T-cell (DN-T) inf

13 In addition, ALPS has been shown to be a more common condition, as pa

14 The analysis was replicated among ALPS trial (Amiodarone, Lidocaine, or Placebo in Out-of-

15 Recently, patients with an ALPS-like disease called RAS-associated autoimmune leuko

16 through a combination of ALPS-dependent and ALPS-independent mechanisms.

17 exes are common features in LGL leukemia and ALPS.

18 Probands and relatives with mutations and ALPS also showed a lower number of CD4(+)/CD25(+) T cell

19 followed by the relatives with mutations and ALPS.

20 ufficient to mildly induce Bim in normal and ALPS T cells via a Janus kinase/signal transducer and ac

21 New work now shows that alpha-synuclein and ALPS motifs represent two extreme types of amphipathic h

22 FAS ligand concentrations were determined as ALPS markers.

23 Diagnostic categories such as ALPS-like disease, common variable immunodeficiency, or

24 se data reveal the nuanced role of the ATG14 ALPS in membrane curvature sensing, suggesting that the

25 nt fraction of shared CDR3 sequences between ALPS DNT and both CD4(+) and CD8(+)TEMRA cells.

26 poptosis in vitro, accounting for biological ALPS phenotypes in vivo.

27 ype was also detected among CD4(+) or CD8(+) ALPS TEMRA cells.

28 F receptor superfamily proteins, but certain ALPS individuals have no such mutations.

29 ar-dynamics (MD) simulations to characterize ALPS binding to such lipid bilayers.

30 tives regardless of the presence of clinical ALPS, factors, other than modifiers of the Fas apoptosis

31 ofile predictive of the presence of clinical ALPS.

32 In conclusion, ALPS is marked by the presence of DR+ T cells that exhib

33 In contrast, ALPS patients' CD4-/CD8- T cells produced very low amoun

34 Definite ALPS patients had a significantly more abnormal in vitro

35 5 patients, 38 met the criteria for definite ALPS and 17 for suspected ALPS.

36 in autoimmune lymphoproliferative diseases (ALPS) and lpr or gld mice and attributed to CD95 and CD9

37 from the discovery dataset, the anterior DTI-ALPS was negatively associated with the expression of th

38 hatic function was evaluated by dividing DTI-ALPS and BOLD-CSF coupling into anterior, middle, and po

39 volume (p < 0.001); anterior and middle DTI-ALPS (p < 0.001); and weaker anterior BOLD-CSF coupling

40 n tensor imaging along the perivascular (DTI-ALPS) index, and coupling between blood-oxygen-level-dep

41 Finally, ALPS patients' peripheral monocytes/macrophages produced

42 s, but without all the required criteria for ALPS (n = 42), had expansions of CD8(+) T cells, alpha/b

43 L-10 and IL-18 are additional indicators for ALPS.

44 elevated sFASLs was a predictive marker for ALPS-FAS group identification.

45 sion of which is virtually pathognomonic for ALPS.

46 that children with ES should be screened for ALPS with DNTs.

47 stic algorithm and recommended treatment for ALPS have changed significantly, improving quality of li

48 e to the cytosolic leaflet is essential for +ALPS binding and vesicular transport between the EE and

49 eases Fas-induced cell death in T cells from ALPS and DALD patients in vitro; and (4) treatment with

50 for somatic FAS mutations in DNT cells from ALPS patients with no detectable germline mutation and a

51 ty for the abnormal allele, lymphocytes from ALPS patients showed markedly decreased FADD association

52 eas no patients with DNTs less than 2.5% had ALPS on apoptosis testing.

53 pothesized a subset of patients with ES have ALPS and tested 45 children at 22 institutions, measurin

54 e immune deficiency, have been found to have ALPS.

55 of 215 patients referred as possibly having ALPS.

56 More than 300 families with hereditary ALPS have now been described; nearly 500 patients from t

57 r terminally differentiated phenotype, human ALPS DNT cells exhibit substantial mitotic activity in v

58 Here we show that human ALPS DNT have features of terminally differentiated effe

59 ALPS is subdivided into: 1) Type Ia, ALPS with mutant Fas; 2) Type Ib, lymphadenopathy and mu

60 th systemic lupus erythematosus; 3) Type II, ALPS with mutant caspase 10; and 4) Type III, ALPS as ye

61 LPS with mutant caspase 10; and 4) Type III, ALPS as yet without any defined genetic cause.

62 We illustrate ALPS through application to a complex gene-drug interact

63 In ALPS, defective lymphocyte apoptosis permits chronic, no

64 correlated significantly with serum IL-10 in ALPS patients, and IL-10 was sufficient to mildly induce

65 therapeutic target for DN T cell ablation in ALPS.

66 apoptosis defects underlying autoimmunity in ALPS type II.

67 ion, leads to organ-specific autoimmunity in ALPS, IPEX, and APS1.

68 ions in caspase-8 have not been described in ALPS, and homozygous caspase-8 deficiency causes embryon

69 roliferation and aberrant differentiation in ALPS.

70 biting Notch signaling would be effective in ALPS and SLE by reducing the production of abnormal DNTs

71 scription 3 pathway drives Bim expression in ALPS DNTC, which renders them sensitive to BH3 mimetics,

72 changes in Bcl-2 family member expression in ALPS to determine whether the Bcl-2 pathway might provid

73 lation of "double-negative" T cells found in ALPS.

74 d therapeutically to improve Fas function in ALPS and DALD.

75 and the Bcl-2 apoptotic pathway intersect in ALPS patients.

76 n the pathogenesis of lymphoproliferation in ALPS patients.

77 sufficiency as a common disease mechanism in ALPS patients with extracellular FAS mutations.

78 S can be disrupted by distinct mechanisms in ALPS.

79 Moreover, in ALPS patients with a germ line FAS mutation and somatic

80 gest that intracytoplasmic CD95 mutations in ALPS impair apoptosis chiefly by disrupting death-domain

81 Mutations in ALPS typically affect CD95 (Fas/APO-1)-mediated apoptosi

82 MZ in ALPS patients contained an abnormally thick layer of MAd

83 d-sparing treatments improves the outcome in ALPS-FAS patients.

84 t likely contribute to disease penetrance in ALPS.

85 ons of the cellular and cytokine profiles in ALPS show a prominent skewing toward a T-helper 2 phenot

86 e in vivo and in vitro cytokine secretion in ALPS to shed light on the relation of apoptosis defects

87 The responses seen in ALPS patients were profound, suggesting that sirolimus s

88 time to CR was often slower than was seen in ALPS.

89 T cells, the pathognomonic T-cell subset in ALPS, in which the somatic events accumulated.

90 toplasmic death domain from nine independent ALPS CD95 death-domain mutations result in a failure to

91 reducing GMAP-210 levels or redirecting its ALPS motif to mitochondria decreased liposome capture by

92 Finally, ABT-737 preferentially killed ALPS DNTC in vitro.

93 ted ALPS (P = .002) and patients not meeting ALPS criteria (P < .001).

94 hydrophobic insertions along the monotonous ALPS sequence.

95 Most ALPS patients harbor mutations in the FAS gene, which re

96 While most ALPS patients carry heterozygous FAS mutations, FASLG mu

97 pamycin is an effective treatment for murine ALPS and should be explored as treatment for affected hu

98 able status compared with 24% (24 of 102) of ALPS patients with the same duration of CPR.

99 understanding of the genetics and biology of ALPS.

100 B12 is a reliable and accurate biomarker of ALPS-FAS, and the major causes of morbidity and mortalit

101 Most cases of ALPS are associated with germline mutations of the FAS g

102 Most cases of ALPS involve heterozygous mutations in the lymphocyte su

103 y on the second allele of FAS, as a cause of ALPS-FAS.

104 ting the FADD gene is a new genetic cause of ALPS.

105 f heterozygous FASLG mutations as a cause of ALPS.

106 A defining characteristic of ALPS is the expansion of double negative T cells (DNTC).

107 monizing the diagnosis and classification of ALPS will foster collaborative research and better under

108 However, analysis of a large cohort of ALPS patients revealed that approximately 30% have mutat

109 after FAS inactivation and a major cohort of ALPS-affected patients were found to have hyper-IgE.

110 gnizes nanovesicles through a combination of ALPS-dependent and ALPS-independent mechanisms.

111 gnaling ask for a more precise definition of ALPS.

112 ested criteria to establish the diagnosis of ALPS.

113 de echogenicity may suggest the diagnosis of ALPS.

114 iently distinctive to suggest a diagnosis of ALPS.

115 thout a Fas mutation and with no features of ALPS (n = 65) demonstrated a small but significant expan

116 ounts for the humoral autoimmune features of ALPS and, perhaps, of other humoral autoimmune states.

117 We show here that the salient features of ALPS as well as a predisposition to hematological malign

118 plex kindred in which biological features of ALPS were found in the context of severe bacterial and v

119 mphocyte apoptosis, but clinical features of ALPS were not present in the vast majority of these indi

120 yte apoptosis and most had other features of ALPS.

121 parents who presented with a severe form of ALPS caused by FASLG deficiency.

122 FAS, which may explain the low frequency of ALPS-FASLG.

123 Notably, hyperproliferation of ALPS DNT cells is associated with increased basal and ac

124 We propose that the hypersensitivity of ALPS motifs to lipid packing defects results from the re

125 s to diagnosis, follow-up, and management of ALPS, its associated cytopenias, and other complications

126 Clinical manifestations of ALPS include autoimmune cytopenias, organomegaly, and ly

127 associated with the overt manifestations of ALPS.

128 RLlpr/lpr mice, which are an animal model of ALPS.

129 ested this hypothesis using murine models of ALPS and SLE.

130 pothesis using rapamycin in murine models of ALPS.

131 ly that better define the pathophysiology of ALPS, including the characterization of somatic FAS vari

132 th domain also showed a higher penetrance of ALPS phenotype features in mutation-bearing relatives.

133 ic loss of heterozygosity was a phenocopy of ALPS-FAS without the more complex symptoms reported in p

134 DNTs (> or = 5%) were a strong predictor of ALPS (positive predictive value = 94%), whereas no patie

135 ycin abrogated survival and proliferation of ALPS DNT cells, but not of CD4(+) or CD8(+) T cells in v

136 hildren with ES and documents a high rate of ALPS among pediatric ES patients.

137 s and determined the in vitro sensitivity of ALPS DNTC to the pro-apoptotic BH3 mimetic, ABT-737.

138 fluences the development and the severity of ALPS.

139 families show an ever-expanding spectrum of ALPS and its major complications: hypersplenism, autoimm

140 inical, genetic, and immunologic spectrum of ALPS, 9 patients and their families were extensively eva

141 The study of ALPS patients reveals the necessity of apoptosis for pre

142 clinical and laboratory phenotype to that of ALPS type Ia.

143 the most useful in identifying all types of ALPS patients; the combination of an abnormal in vitro a

144 ed in clinical and basic science research on ALPS and related disorders.

145 One ALPS patient lacked a Fas gene mutation.

146 h somatic FAS mutations among a group of our ALPS patients with no detectable germline mutation and t

147 levated immunoglobulin levels also predicted ALPS.

148 ng both a Fas mutation and clinically proven ALPS (n = 28) showed significant expansion of CD8(+) T c

149 a known vascular access site, 2358 received ALPS drugs intravenously and 661 patients by the intraos

150 This proposed approach to redefining ALPS and other lymphoproliferative conditions provides a

151 ntrinsic amphipathic lipid packaging sensor (ALPS) motif within HOPS Vps41, a target of the vacuolar

152 -targeting amphipathic lipid packing sensor (ALPS) motif of ATG14.

153 hat of the amphipathic lipid-packing sensor (ALPS) motif of GMAP-210: both preferred small (radius <

154 nsors, the Amphipathic Lipid Packing Sensor (ALPS) motif, does not seem to recognize the curved surfa

155 within an amphipathic lipid-packing sensor (ALPS) motif, which participates in targeting of synapsin

156 ures of an amphipathic lipid packing sensor (ALPS) motif, which, in other proteins, enables membrane

157 An amphipathic lipid packing sensor (ALPS)-like helix within the loop directly binds high-cur

158 variant of the ArfGAP lipid packing sensor (+ALPS) motif for localization to TGN/EE membranes.

159 t be identified on standard exon sequencing (ALPS-undetermined: ALPS-U).

160 otoxicity and resulted in early-onset severe ALPS with elevated DNT, raised vitamin B(12), and usuall

161 Significant ALPS-related morbidity occurred in 44% of relatives with

162 Since ALPS is caused by defective lymphocyte apoptosis, we hyp

163 imilar to ALPS type Ia patients, the somatic ALPS patients had increased DNT cell numbers and elevate

164 aging analysis along the perivascular space (ALPS) index, is involved in developmental neuropsychiatr

165 The Antenatal Late Preterm Steroids (ALPS) trial changed clinical practice in the United Stat

166 The Antenatal Late Preterm Steroids (ALPS) trial demonstrated a 20% reduction in the risk of

167 tion of the Antenatal Late Preterm Steroids (ALPS) trial in February 2016 demonstrated that antenatal

168 he algorithm for learning pathway structure (ALPS), which addresses key limitations in existing appro

169 In parallel in vitro studies, ALPS patients CD4+ DR+ T cells stimulated either with an

170 In in vivo studies, ALPS patients manifested greatly increased circulating l

171 The definite and suspected ALPS patient populations showed higher DNT percentages t

172 teria for definite ALPS and 17 for suspected ALPS.

173 lower annexin, than patients with suspected ALPS (P = .002) and patients not meeting ALPS criteria (

174 ith autoimmune lymphoproliferative syndrome (ALPS) achieved a durable complete response (CR), includi

175 The autoimmune lymphoproliferative syndrome (ALPS) affords novel insights into the mechanisms that re

176 ith autoimmune lymphoproliferative syndrome (ALPS) and dominantly interfere with apoptosis by an unkn

177 ith autoimmune lymphoproliferative syndrome (ALPS) and systemic lupus erythematosis (SLE) have T-cell

178 the autoimmune lymphoproliferative syndrome (ALPS) are usually attributable to inherited mutations of

179 Autoimmune lymphoproliferative syndrome (ALPS) caused by impaired FAS-mediated apoptosis of lymph

180 use autoimmune-lymphoproliferative syndrome (ALPS) characterized by expanded double-negative T cells

181 Autoimmune lymphoproliferative syndrome (ALPS) in humans and lymphoproliferative (LPR) disease in

182 ere autoimmune lymphoproliferative syndrome (ALPS) in humans.

183 Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caus

184 Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caus

185 Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of disrupted lymphocyte homeostasis,

186 Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte homeostasis and immuno

187 Autoimmune lymphoproliferative syndrome (ALPS) is a genetically defined inborn error of immunity

188 Autoimmune lymphoproliferative syndrome (ALPS) is a human disorder characterized by defective Fas

189 Autoimmune lymphoproliferative syndrome (ALPS) is a human disorder of T cell homeostasis caused b

190 Autoimmune lymphoproliferative syndrome (ALPS) is a human genetic disorder of lymphocyte apoptosi

191 The autoimmune lymphoproliferative syndrome (ALPS) is a noninfectious and nonmalignant lymphoprolifer

192 Autoimmune lymphoproliferative syndrome (ALPS) is a rare immunodeficiency caused by mutations in

193 Autoimmune Lymphoproliferative Syndrome (ALPS) is a recently recognized disease in which a geneti

194 Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder in which genetic defects

195 Autoimmune lymphoproliferative syndrome (ALPS) is caused by inactivating mutations in FAS or FASL

196 Autoimmune lymphoproliferative syndrome (ALPS) is characterized by childhood onset of lymphadenop

197 Autoimmune lymphoproliferative syndrome (ALPS) is characterized by chronic nonmalignant lymphopro

198 The autoimmune lymphoproliferative syndrome (ALPS) is characterized by early-onset lymphadenopathy, s

199 se, Autoimmune Lymphoproliferative Syndrome (ALPS) is due to dominant-interfering mutations in the Fa

200 Autoimmune lymphoproliferative syndrome (ALPS) is marked by massive lymphadenopathy, hepatospleno

201 Autoimmune lymphoproliferative syndrome (ALPS) is the most common genetic disease of lymphocyte a

202 the autoimmune lymphoproliferative syndrome (ALPS) met in Bethesda, Maryland on September 21-22, 2009

203 ith autoimmune lymphoproliferative syndrome (ALPS) patients and healthy mutation-positive relatives,

204 in autoimmune lymphoproliferative syndrome (ALPS) patients.

205 Autoimmune lymphoproliferative syndrome (ALPS) presents in childhood with nonmalignant lymphadeno

206 Autoimmune lymphoproliferative syndrome (ALPS) represents a failure of apoptotic mechanisms to ma

207 the autoimmune lymphoproliferative syndrome (ALPS) reveals that formation of SPOTS can be disrupted b

208 Autoimmune lymphoproliferative syndrome (ALPS) type Ia is caused by inherited defects in apoptosi

209 ith autoimmune lymphoproliferative syndrome (ALPS) type II, characterized by abnormal lymphocyte and

210 ith autoimmune lymphoproliferative syndrome (ALPS), a congenital disease of defective apoptosis and a

211 of autoimmune lymphoproliferative syndrome (ALPS), a human disorder that is characterized by defecti

212 of autoimmune lymphoproliferative syndrome (ALPS), caused by mutation of the Fas death receptor, is

213 In autoimmune/lymphoproliferative syndrome (ALPS), defective Fas death receptor function causes lymp

214 the autoimmune lymphoproliferative syndrome (ALPS), which is caused by mutations in the FAS apoptotic

215 ted autoimmune lymphoproliferative syndrome (ALPS).

216 ith autoimmune lymphoproliferative syndrome (ALPS).

217 ith autoimmune lymphoproliferative syndrome (ALPS).

218 of autoimmune lymphoproliferative syndrome (ALPS).

219 ith autoimmune lymphoproliferative syndrome (ALPS; Canale-Smith syndrome), a disorder of lymphocyte h

220 tated in the congenital autoimmune syndrome, ALPS.

221 mon cause of this condition, which is termed ALPS-FAS.

222 s mediated exclusively by the amino-terminal ALPS motif.

223 The ALPS motif recognizes lipid-packing defects by a conserv

224 The ALPS type Ia probands (n = 31) and relatives having both

225 Among the ALPS-associated Fas mutants, dominant inhibition of apop

226 mon underlying genetic mechanism between the ALPS-index, ventricular volumes, and cerebrospinal fluid

227 Furthermore, the ALPS motif and VPS34 catalytic activity are required for

228 no neurologically favorable survivors in the ALPS cohort with CPR >=40 minutes, whereas neurologicall

229 an antiarrhythmic drug versus placebo in the ALPS trial (Resuscitation Outcomes Consortium Amiodarone

230 nodeficiencies, we propose a revision of the ALPS classification, restricting use of this term to con

231 ion of Thr-87 interferes with folding of the ALPS motif, providing a means for regulating the associa

232 ed standard CPR in the amiodarone arm of the ALPS trial (Amiodarone, Lidocaine, or Placebo Study).

233 Public dissemination of the ALPS trial results, which occurred during a 9-month peri

234 ths associated with the dissemination of the ALPS trial, suggesting that this evidence may be transla

235 nce the understanding of the genetics of the ALPS-index and provide insight for further research into

236 brane curvature sensing, suggesting that the ALPS has additional roles in supporting LC3 lipidation.

237 t loci and 161 candidate genes linked to the ALPS-indexes in a discovery sample of 31,021 individuals

238 vesicles via the same mechanism whereby the ALPS motif senses lipid-packing defects at the vesicle s

239 ic leaflet, both of which are sensed by the +ALPS motif.

240 a potentially novel therapeutic approach to ALPS.

241 icate that these cytokines may contribute to ALPS and DALD: (1) recombinant IL-17A and IL-17F signifi

242 Some authors have referred to ALPS as Canale-Smith syndrome or lymphoproliferative syn

243 Similar to ALPS type Ia patients, the somatic ALPS patients had inc

244 e mofetil, a second-line agent used to treat ALPS, and found rapamycin's control of lymphoproliferati

245 hat rapamycin would be effective in treating ALPS.

246 standard exon sequencing (ALPS-undetermined: ALPS-U).

247 rituximab have been shown to have unexpected ALPS-specific toxicities, and mycophenolate mofetil and

248 orized into definite, suspected, or unlikely ALPS groups, and laboratory parameters were compared amo

249 showed higher DNT percentages than unlikely ALPS and had higher rates of lymphoproliferation.

250 Of 17 unique APT1 mutations in unrelated ALPS probands, 12 (71%) occurred in exons 7-9, which enc

251 ssembled into full length LC sequences using ALPS.

252 the characterization of somatic FAS variant ALPS, the identification of haploinsufficiency as a mech

253 ificantly higher in UMN-ECPR patients versus ALPS patients (33% versus 23%; P=0.01) overall.

254 ficantly longer for UMN-ECPR patients versus ALPS patients (60 minutes versus 35 minutes; P<0.001).

255 ta revealed an unexpected mechanism by which ALPS results in anti-polysaccharide IgM antibody product

256 stasis but, unlike individuals affected with ALPS, also have defects in their activation of T lymphoc

257 survival for UMN-ECPR patients compared with ALPS patients at each CPR duration interval <60 minutes;

258 ical features and biomarkers consistent with ALPS, germline or somatic FAS mutations cannot be identi

259 findings in 166 members of 31 families with ALPS type Ia, associated with genetic mutations in the T

260 expression of Eomes in humans and mice with ALPS.

261 This work shows that patients with ALPS and DALD have high serum levels of interleukin 17A

262 When lymphocytes from patients with ALPS are cultured in vitro, they are resistant to apopto

263 Treatment options for patients with ALPS are limited.

264 e disease onset in 4 unrelated patients with ALPS carrying a germline monoallelic mutation of the FAD

265 and lymphoid tissues of these patients with ALPS contained significantly higher levels of IL-10 mess

266 Patients with ALPS demonstrate nonspecific but often dramatic imaging

267 Patients with ALPS have chronic enlargement of the spleen and lymph no

268 Most patients with ALPS have mutations in a gene now named TNFRSF6 (tumor n

269 Some patients with ALPS have relatives with these same apoptotic defects, h

270 e then, with approximately 500 patients with ALPS studied worldwide, significant advances in our unde

271 icantly higher (P <.001) in 21 patients with ALPS than in healthy controls.

272 Patients with ALPS typically present with no other clinical phenotype.

273 cal features in 19 consecutive patients with ALPS were performed.

274 an accurate means to identify patients with ALPS who are missed by routine exome sequencing.

275 optosis have been described in patients with ALPS, including the FAS ligand gene (FASLG) in rare case

276 as variants, not restricted to patients with ALPS, were identified.

277 Despite this progress, many patients with ALPS-like disease remain undefined genetically.

278 Nine of 16 patients with ALPS-U lacked FAS expression on CD57(+)DNT predicting he

279 umoral autoimmunity typical of patients with ALPS.

280 3), and liver (n = 2) from 10 patients with ALPS.

281 apoptosis in only a subset of patients with ALPS.

282 ould be screened in patients presenting with ALPS features but lacking the usual markers, including p