ライフサイエンスコーパス: CVID

1 CVID patients displayed significantly elevated plasma le

2 CVID patients have considerable autoimmune comorbidity a

3 CVID patients underwent tests of gut absorption, periphe

4 CVID patients with gastrointestinal symptoms differed fr

5 CVID patients with GLILD (CVID-GLILD), 1/21 CVID patients without GLILD (CVID-control), and no patie

6 immune cell populations was performed in 46 CVID patients and 44 healthy donors.

7 dy performed in CVID to date, we compare 778 CVID cases with 10,999 controls across 123,127 single-nu

8 It was positive in 6/9 CVID patients with GLILD (CVID-GLILD), 1/21 CVID patient

9 to predispose (TNFRSF13B [n = 3]) or cause a CVID-like primary immunodeficiency (CTLA4 [n = 2], KMT2D

10 n addition, Nfkb2 mouse models demonstrate a CVID-like phenotype with hypogammaglobulinemia and poor

11 function, and TACI-deficient mice exhibit a CVID-like disease.

12 We identified a CVID+AIC patient who displays a rare homozygous missense

13 on 9 skipping mutation (c.835+2T>G) and in a CVID-affected family from New Zealand with a heterozygou

14 CpG-activated CVID plasmacytoid dendritic cells did not produce IFN-al

15 In addition, CVID was found to be associated with increased plasma le

16 GC responses in patients with CVID with AIC (CVID+AIC) and without AIC (CVID-AIC).

17 th CVID with AIC (CVID+AIC) and without AIC (CVID-AIC).

18 D subjects with autoimmune cytopenias (AICs; CVID+AIC) and the causes of these derangements.

19 Although CVID is thought to be a disorder of the peripheral B-cel

20 f autoreactive B cells in healthy donors and CVID patients.

21 ) T(H) cell profiles from healthy donors and CVID subjects without AICs were virtually indistinguisha

22 be considered in children with SLE, ES, and CVID.

23 kpoints, we analyzed healthy individuals and CVID patients carrying one or two TACI mutations.

24 A majority of CD21(-/lo) B cells from RA and CVID patients expressed germline autoreactive antibodies

25 ding JIA, SLE, CEL, T1D, UC, CD, PS, SPA and CVID, attributable to common genomic variations (SNP-h(2

26 testinal symptoms differed from asymptomatic CVID patients by having significantly longer duration of

27 In a Dutch-Australian CVID-affected family, we identified a NFKB1 heterozygous

28 s had GS and 440 had CVID, including 39 B(-) CVID, with a median age at diagnosis of 60, 35, and 34 y

29 GS differs notably from CVID and B(-) CVID: very late onset, no familial cases, and absence of

30 in 90.5% of GS, 54% of CVID, and 72% of B(-) CVID patients.

31 d in 76% of GS, 29% of CVID, and 26% of B(-) CVID patients.

32 nor lymphoma, unlike those with CVID or B(-) CVID.

33 immunodeficiency (CVID), and those with B(-) CVID (circulating B cells <1%) were performed.

34 milies in whom male members were affected by CVID were examined for a defect in the XLP gene.

35 Clinically, CVID is a truly variable antibody deficiency syndrome.

36 For the US and Swedish cohorts, CVID subjects with noninfectious complications, lymphoid

37 etry, was applied to patients with confirmed CVID in comparison with age-matched healthy control subj

38 play an increase of CD21(low) B-cell counts (CVID 21low), whereas others do not (CVID 21norm).

39 ciency associated with autoimmune cytopenia (CVID+AIC) generate few isotype-switched B cells with sev

40 ents with common variable immune deficiency (CVID) an increased risk for autoimmunity.

41 iency and common variable immune deficiency (CVID) in humans.

42 Common variable immune deficiency (CVID) is a primary immune deficiency characterized by lo

43 Common variable immune deficiency (CVID) is a primary immunodeficiency disease, characteriz

44 Common variable immune deficiency (CVID) is an assorted group of primary diseases that clin

45 Common variable immune deficiency (CVID) is one of the most common congenital immune defect

46 sified as common variable immune deficiency (CVID), although other genes, including some not yet iden

47 ents with common variable immune deficiency (CVID).

48 e follicular T-cell lineage in IgA-deficient CVID subjects, particularly those with AICs.

49 ines produced by LPMCs from Crohn's disease, CVID patients did not produce excess amounts of interleu

50 Common variable immunodeficiency disorder (CVID) is the most common symptomatic primary immunodefic

51 h common variable immunodeficiency disorder (CVID), which was recognizable by a support vector machin

52 Common variable immunodeficiency disorders (CVID) represent a group of primary immunodeficiency dise

53 common variable immunodeficiency disorders (CVIDs), predominating.

54 B cell-targeted therapy might disrupt CVID-associated lymphoid hyperplasia.

55 entified in a family with autosomal dominant CVID.

56 Thus, TACI mutations may favor CVID by altering B cell activation with coincident impai

57 s a novel potential therapeutic strategy for CVID.

58 s for developing a novel diagnostic tool for CVID.

59 ment was more profound in naive B cells from CVID 21low patients than CVID 21norm patients and most p

60 , circulating follicular helper T cells from CVID+AIC subjects exhibited aberrant transcriptional pro

61 re virtually indistinguishable, T cells from CVID+AIC subjects exhibited follicular features as early

62 Similar to the mice, Ig S joints from CVID and IgA deficiency patients carrying disease-associ

63 Neutrophils from CVID patients actively suppressed T cell activation and

64 notypic changes observed on neutrophils from CVID patients and induced neutrophil population with LDN

65 Neutrophils from CVID patients exhibited elevated surface levels of CD11b

66 GS differs notably from CVID and B(-) CVID: very late onset, no familial cases,

67 ing follicular helper T-cell population from CVID+AIC subjects provided efficient help to receptive h

68 Furthermore, CVID was associated with an increased frequency of low-d

69 HC region, supporting that this is a genuine CVID locus.

70 proteins were also undetectable in a German CVID-affected family with a heterozygous in-frame exon 9

71 as positive in 6/9 CVID patients with GLILD (CVID-GLILD), 1/21 CVID patients without GLILD (CVID-cont

72 ID-GLILD), 1/21 CVID patients without GLILD (CVID-control), and no patients receiving intravenous gam

73 Twenty-one patients had GS and 440 had CVID, including 39 B(-) CVID, with a median age at diagn

74 etically, and they were classified as having CVID.

75 T cell dysfunction regularly found in human CVID.

76 duals with common variable immunodeficiency (CVID) and 1 of 16 individuals with IgA deficiency (IgAD)

77 s who have common variable immunodeficiency (CVID) and granulomatous/lymphocytic interstitial lung di

78 ients with common variable immunodeficiency (CVID) comprises a heterogeneous group of patients with d

79 ients with common variable immunodeficiency (CVID) disorders display impairment in production of immu

80 ients with common variable immunodeficiency (CVID) experience immune dysregulation manifesting as aut

81 duals with common variable immunodeficiency (CVID) express either the C104R or A181E variants of TACI

82 Although common variable immunodeficiency (CVID) has long been considered as a group of primary Ab

83 ients with common variable immunodeficiency (CVID) have debilitating inflammatory complications stron

84 Common variable immunodeficiency (CVID) is a disease characterized by increased susceptibi

85 Common variable immunodeficiency (CVID) is a disease that is characterized primarily by lo

86 Common variable immunodeficiency (CVID) is a disorder characterized by antibody deficiency

87 Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by antib

88 Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by B-cel

89 Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by impai

90 Common variable immunodeficiency (CVID) is a syndrome characterized by immunoglobulin defi

91 Common variable immunodeficiency (CVID) is an antibody deficiency treated with immunoglobu

92 Common variable immunodeficiency (CVID) is an antibody deficiency with an equal sex distri

93 Common variable immunodeficiency (CVID) is an immune disorder that not only causes increas

94 Common variable immunodeficiency (CVID) is characterized by late-onset hypogammaglobulinem

95 Common variable immunodeficiency (CVID) is characterized clinically by inadequate quantity

96 feature of common variable immunodeficiency (CVID) is hypogammaglobulinemia (HG).

97 Common variable immunodeficiency (CVID) is the commonest symptomatic primary antibody diso

98 Common variable immunodeficiency (CVID) is the primary immunodeficiency most commonly enco

99 Common variable immunodeficiency (CVID) patients can develop an idiopathic inflammatory bo

100 ncy in 235 common variable immunodeficiency (CVID) patients seen in the United States (Mount Sinai, N

101 ses and in common variable immunodeficiency (CVID) patients who are prone to autoimmunity.

102 cells from common variable immunodeficiency (CVID) patients who have one mutant copy of the gene enco

103 ients with common variable immunodeficiency (CVID) present with severely reduced switched memory B-ce

104 identified common variable immunodeficiency (CVID) subjects with numeric and/or functional T(H) cell

105 ients with common variable immunodeficiency (CVID) suggests germinal center (GC) hypoplasia, yet a su

106 ients with common variable immunodeficiency (CVID) where the effect of the humoral immune system is r

107 ients with common variable immunodeficiency (CVID) who are heterozygous for transmembrane activator a

108 ients with common variable immunodeficiency (CVID), 68 patients with selective IgA deficiency (IgAdef

109 those with common variable immunodeficiency (CVID), and those with B(-) CVID (circulating B cells <1%

110 ients with common variable immunodeficiency (CVID), but the optimal treatment is unknown.

111 Common variable immunodeficiency (CVID), characterized by recurrent infections, is the mos

112 condary to common variable immunodeficiency (CVID), Evans syndrome (ES), or systemic lupus erythemato

113 ients with common variable immunodeficiency (CVID), including production of cytokines and proliferati

114 Common variable immunodeficiency (CVID), the most frequent symptomatic primary immune defi

115 r focus on common variable immunodeficiency (CVID).

116 ients with common variable immunodeficiency (CVID).

117 ients with common variable immunodeficiency (CVID).

118 tient with common variable immunodeficiency (CVID).

119 jects with common variable immunodeficiency (CVID).

120 ients with common variable immunodeficiency (CVID).

121 iated with common variable immunodeficiency (CVID).

122 ow circulating CD4(+) T cells are altered in CVID subjects with autoimmune cytopenias (AICs; CVID+AIC

123 In conclusion, the CLEC16A associations in CVID represent the first robust evidence of non-HLA asso

124 of the function and number of iNKT cells in CVID.

125 t there are broad TLR9 activation defects in CVID which would prevent CpG-DNA-initiated innate immune

126 ic mechanisms mediating immune deficiency in CVID remain to be determined.

127 e-activated normal B cells, was deficient in CVID B cells, as was TLR9 mRNA.

128 ous-lymphocytic interstitial lung disease in CVID), and an increased risk of lymphoma.

129 and the development of autoimmune disease in CVID.

130 s and consequences of microbial dysbiosis in CVID.

131 udies indicated that immune dysregulation in CVID patients is associated with chronic microbial trans

132 of inflammation and immune dysregulation in CVID, and suggest research strategies to contribute to t

133 f NF-kappaB signaling defects, especially in CVID 21low patients, suggests a broad underlying signali

134 lexity of the immunologic phenotype found in CVID syndrome.

135 myeloid-derived suppressor cell frequency in CVID patients correlated with reduced T cell responsiven

136 termined the prevalence of HHV8 infection in CVID patients with GLILD.

137 centers suggest tertiary lymphoneogenesis in CVID-associated lung disease.

138 One of the 2 most common TACI mutations in CVID, A181E, introduces a negative charge into the trans

139 ustion and functional impairment observed in CVID patients is associated with bacterial translocation

140 asia, different from the pattern observed in CVID patients.

141 or inflammatory conditions may also occur in CVID, and indeed these may be the first and only sign th

142 RA to improve critical immune parameters in CVID-derived B cells stimulated through TLR9 and RP105 s

143 e, in the largest genetic study performed in CVID to date, we compare 778 CVID cases with 10,999 cont

144 other B cell and T cell findings reported in CVID remains unclear.

145 to restore the defective immune responses in CVID-derived B cells activated through the TLRs TLR9 and

146 ts suggest that TACI mutations can result in CVID and IgAD.

147 tion and nuclear translocation, resulting in CVID with adrenocorticotropic hormone deficiency, growth

148 out whether the plasma protein signature in CVID is associated with clinical characteristics and lym

149 associated with gastrointestinal symptoms in CVID is a unique combination of diverse histologic findi

150 of the role of genetic variations in TACI in CVID populations has improved our understanding of possi

151 n the development of immune dysregulation in CVIDs has become more apparent.

152 ID, suggesting that TACI mutations influence CVID pathogenesis via dominant interference or haploinsu

153 he diseases UC-CD (0.69+/-s.e. 0.07) and JIA-CVID (0.343+/-s.e. 0.13) are the most strongly correlate

154 alpha and antiviral chemotherapy in managing CVID-associated inflammatory disease.

155 B signaling was impaired in all mature naive CVID-derived B cells.

156 on cells from patients with noninflammatory CVID and healthy subjects.

157 counts (CVID 21low), whereas others do not (CVID 21norm).

158 tions were demonstrated in 76% of GS, 29% of CVID, and 26% of B(-) CVID patients.

159 ections were observed in 90.5% of GS, 54% of CVID, and 72% of B(-) CVID patients.

160 In approximately 90% of CVID-affected individuals, no genetic cause of the disea

161 nd provide new knowledge on the aetiology of CVID.

162 We report a novel association of CVID with rare variants at the FUS/ITGAM (CD11b) locus o

163 een uncovered, and the genetic background of CVID remains elusive to date for the majority of patient

164 demonstrate that neutrophils in the blood of CVID patients acquire an activated phenotype and exert p

165 To investigate the molecular cause of CVID, we carried out exome sequence analysis of a family

166 However, rare monogenic causes of CVID might lack such a genetic fingerprint.

167 remains elusive, a common characteristic of CVID is deficient IgG Ab production in response to infec

168 D8 ratio inversion that is characteristic of CVID.

169 estigation of blood samples from a cohort of CVID patients; revealing spectral features capable of st

170 in a large and genetically diverse cohort of CVID subjects (n = 69) by using flow cytometry, transcri

171 targeted therapies for this complication of CVID.

172 ses, interrelationships, and consequences of CVID-associated CD4(+) T-cell derangements to hypogammag

173 The diagnostic delay of CVID ranges between 4 and 5 years in many countries and

174 ation might contribute to the development of CVID disorders.

175 ly with multiple members with a diagnosis of CVID was screened by using whole-exome sequencing.

176 A patient given a diagnosis of CVID, who was born to a consanguineous family and thus w

177 does not recapitulate autoimmune features of CVID-associated C104R and A181E TNFRSF13B mutations, whi

178 IKAROS caused an autosomal dominant form of CVID that is associated with a striking decrease in B-ce

179 The clinical heterogeneity of CVID has hindered identification of an underlying immune

180 the innate immune system in pathogenesis of CVID has begun to emerge.

181 ole of the microbiome in the pathogenesis of CVID immune dysregulation, and describe the possible imm

182 ctor (TACI) mutations in the pathogenesis of CVID was further described and reported to be likely med

183 re for the first time in the pathogenesis of CVID.

184 the bone marrow niche in the pathogenesis of CVID.

185 aimed to better understand the pathology of CVID-associated lung disease.

186 mutations cosegregated with the phenotype of CVID or IgAD in family members of four index individuals

187 E TACI variants and have no outward signs of CVID, and it is not clear why TACI deficiency in this gr

188 ormation might predispose to the spectrum of CVID disorders.

189 toire diversity between various subgroups of CVID patients according to their B cell immunophenotypes

190 RA with TLR stimulation for the treatment of CVID.

191 Research into the cause of CVIDs has made use of the increased understanding of imm

192 NA did not up-regulate expression of CD86 on CVID B cells, even when costimulated by the BCR, or indu

193 One CVID-GLILD patient developed a B cell lymphoma during th

194 Male subjects with early-onset CVID were more prone to pneumonia and less prone to othe

195 rticularly high in subjects with early-onset CVID.

196 population of patients with pediatric-onset CVID to clinically correlate and assess their ability to

197 D27 as genetically dissimilar from polygenic CVID.

198 ack the genetic pattern present in polygenic CVID cases.

199 ed through the SVM algorithm from our recent CVID genome-wide association study.

200 presented with a clinical picture resembling CVID.

201 is likely a monogenic cause of the family's CVID phenotype.

202 , and poor Ab responses to vaccine in severe CVID patients.

203 d isotype switching in TLR9/RP105-stimulated CVID-derived B cells owing to reduced induction of activ

204 ing spectral features capable of stratifying CVID patients from healthy controls with sensitivities a

205 Symptomatic CVID patients showed diffuse histologic inflammatory cha

206 LPMCs from symptomatic CVID patients produced significantly higher T-helper (Th

207 travenous immunoglobulin preparations target CVID gut microbiota much less efficiently than healthy m

208 naive B cells from CVID 21low patients than CVID 21norm patients and most pronounced in CD21(low) B

209 Thus, data indicate that CVID-associated immune dysregulation is a T(H)1-mediated

210 0 proteins were absent, we conclude that the CVID phenotype in these families is caused by NF-kappaB1

211 Two cohorts could be discerned within the CVID group: group 1 with an abnormal number of iNKT cell

212 C104R TACI mutation can potentially lead to CVID.

213 n immune regulatory pathways of relevance to CVID.

214 hypothesized that genetic susceptibility to CVID may overlap with autoimmune disorders.

215 ubsequent screening of NFKB2 in 33 unrelated CVID-affected individuals uncovered a second heterozygou

216 e healthy donor B cells but not unresponsive CVID B cells.

217 superfamily member TACI are associated with CVID and autoimmune manifestations, whereas two mutated

218 (SNPs) at the 16p11.2 locus associated with CVID at a genome-wide significant level in the discovery

219 ther subjects with mutations associated with CVID-like phenotypes were screened through the SVM algor

220 cell number or function was associated with CVID.

221 ion frequencies than their counterparts with CVID-AIC.

222 sequence analysis of a family diagnosed with CVID and identified a heterozygous frameshift mutation,

223 One of the four individuals with CVID had a single nucleotide insertion in the other TNFR

224 sidered when more than one male patient with CVID is encountered in the same family, and SH2D1A must

225 ured in peripheral blood of 55 patients with CVID (31 with and 24 without inflammatory/autoimmune com

226 s were systematically found in patients with CVID (absent in 98%), with 6 different defective MBC (an

227 mutation was more frequent in patients with CVID (n = 53, P < .013).

228 s in a discovery cohort of 164 patients with CVID and 19,542 healthy control subjects genotyped on th

229 n an independent cohort of 135 patients with CVID and 2,066 healthy control subjects, followed by met

230 ry enumerated iNKT cells in 36 patients with CVID and 50 healthy controls.

231 roduction was observed between patients with CVID and controls.

232 ical and laboratory data on 39 patients with CVID and GLILD who completed immunosuppressive therapy w

233 onary function test results in patients with CVID and GLILD.

234 zation to evaluate a subset of patients with CVID and low B-cell numbers.

235 Patients with CVID are being managed differently throughout Europe, af

236 paB) signaling in B cells from patients with CVID as a central pathway in B-cell differentiation.

237 vitro activation revealed that patients with CVID behaved heterogeneously in terms of responsiveness

238 etectable in the lungs of most patients with CVID by CT scanning, not all patients develop lung compl

239 1 iNKT cells/10(5) T cells) in patients with CVID compared with healthy controls (100 iNKT cells/10(5

240 d follicular helper T cells of patients with CVID compared with those of healthy control subjects.

241 e and IgM(+) memory B cells of patients with CVID compared with those of healthy donors, whereas the

242 n primary B cells of pediatric patients with CVID disorders and healthy control subjects.

243 Instead, B cells from patients with CVID disorders exhibited reduced BCR dissociation from C

244 In many pediatric patients with CVID disorders, B cells exhibit significant deficits in

245 Data on 2212 patients with CVID from 28 medical centers contributing to the Europea

246 cle discusses 3 cases in which patients with CVID had some of these presenting issues and what hemato

247 rogeneity of memBc function in patients with CVID homogenously grouped by means of fluorescence-activ

248 C) hypoplasia, yet a subset of patients with CVID is paradoxically affected by autoantibody-mediated

249 dentified 2 distinct groups of patients with CVID that differed significantly in terms of the degree

250 ls in blood and lymph nodes of patients with CVID using flow cytometry, analyzed their function, and

251 Expression in patients with CVID was associated with anaphylaxis on IVIg infusion (P

252 utions per year, compared with patients with CVID with a rate of 0.415 nucleotide substitutions per y

253 files delineated a subgroup of patients with CVID with activated T cells and clinical complications d

254 ogic output of GC responses in patients with CVID with AIC (CVID+AIC) and without AIC (CVID-AIC).

255 The B cells of patients with CVID with CD21(low) B-cell expansion resemble anergic B

256 ut not in the naive B cells of patients with CVID with CD21(low) expansion.

257 ed them with counterparts from patients with CVID with heterozygous C104R or A181E TNFRSF13B missense

258 mmunologic features typical of patients with CVID with heterozygous TNFRSF13B missense mutations.

259 Patients with CVID with immune dysregulation had a skewed memory CD4 T

260 lymph node-derived T cells of patients with CVID with immune dysregulation will offer new therapeuti

261 were expanded in the blood of patients with CVID with inflammatory conditions (mean, 3.7% of PBMCs).

262 ulation is a characteristic of patients with CVID with inflammatory disease; ILCs and the interferon

263 s and pathologic findings of 6 patients with CVID with nodular/infiltrative lung disease who had biop

264 of an interferon signature in patients with CVID with secondary complications and a skewed follicula

265 node biopsy specimens from 14 patients with CVID+AIC and 4 patients with CVID-AIC.

266 We found that patients with CVID+AIC displayed irregularly shaped hyperplastic GCs,

267 Patients with CVID+AIC do not contain mucosal microbiota and exhibit h

268 Moreover, IgG(+) B cells from patients with CVID+AIC expressed VH4-34-encoded antibodies with unmuta

269 In addition, patients with CVID+AIC had serum endotoxemia associated with a dearth

270 In some patients with CVID, a defective btk or CD40-L gene has been found, but

271 with inflammatory pathology in patients with CVID, explain some of the well-known T-cell abnormalitie

272 of immune dysfunction in some patients with CVID, have enabled advances in the clinical classificati

273 vestigate whether B cells from patients with CVID, like anergic B cells, have defects in extracellula

274 nal and lung biopsy tissues of patients with CVID, numerous IFN-gamma(+)RORgammat(+)CD3(-) cells were

275 ns were found in the plasma of patients with CVID, suggesting that CD4 T cell dysfunction might be ca

276 s GCs were scarce and small in patients with CVID-AIC.

277 4 patients with CVID+AIC and 4 patients with CVID-AIC.

278 liver, and bone marrow of four patients with CVID-GLILD.

279 ot previously been explored in patients with CVID.

280 phoproliferation (P = .002) in patients with CVID.

281 o be intrinsic to B cells from patients with CVID.

282 onally impaired in most of the patients with CVID.

283 n contribute to anaphylaxis in patients with CVID.

284 et is expanded in CMV-infected patients with CVID.

285 e effector cell populations in patients with CVID.

286 ut bacterial translocations in patients with CVID.

287 mphoproliferative disorders in patients with CVID.

288 A must be analyzed in all male patients with CVID.

289 ents and antibody responses in patients with CVID.

290 icians to further characterize patients with CVID.

291 g of 145 plasma proteins in 29 patients with CVID.

292 e memory formation observed in patients with CVID.

293 ons in both TACI alleles do not present with CVID, suggesting that TACI mutations influence CVID path

294 ects with mutations, including subjects with CVID and relatives.

295 Thus, B cells of relatives of subjects with CVID who have mutations in TACI but normal immune globul

296 healthy relatives but not for subjects with CVID.

297 hyperplasia nor lymphoma, unlike those with CVID or B(-) CVID.

298 eficiency with IgA deficiency and those with CVID showed defects in both smIgA(+) and smIgG(+) MBCs a

299 n B cells of healthy patients and those with CVID.

300 ociations of genes and genetic variants with CVID.