ライフサイエンスコーパス: primary immunodeficiency

1 tly increases the diagnostic yield of severe primary immunodeficiency.

2 ogy, motility, and function, causing a novel primary immunodeficiency.

3 , and failure to thrive, but without obvious primary immunodeficiency.

4 ) T cell count in the setting of HIV/AIDS or primary immunodeficiency.

5 that lesions in this miRNA gene may lead to primary immunodeficiency.

6 d that its depletion underlies a novel human primary immunodeficiency.

7 daptor MyD88 or the kinase IRAK4 suffer from primary immunodeficiency.

8 r (IL-21R) deficiencies as novel entities of primary immunodeficiency.

9 ections, thus characterizing the disorder as primary immunodeficiency.

10 ecome a first-line tool for the diagnosis of primary immunodeficiency.

11 isease in children may be a manifestation of primary immunodeficiency.

12 tire spectrum of malignancies is not seen in primary immunodeficiency.

13 is also an underappreciated manifestation of primary immunodeficiency.

14 of lymphoid malignancy in the many types of primary immunodeficiency.

15 ith immune dysregulation, rather than a mere primary immunodeficiency.

16 WES in a global population of patients with primary immunodeficiency.

17 s in any of the four known ICF genes cause a primary immunodeficiency.

18 ence of immune dysfunction, despite no known primary immunodeficiency.

19 he T cell lymphopenia characteristic of this primary immunodeficiency.

20 th chronic skin granuloma in 3 children with primary immunodeficiency.

21 iseases, including cancer, inflammation, and primary immunodeficiencies.

22 n several clinical examples of patients with primary immunodeficiencies.

23 coding components of the immune system cause primary immunodeficiencies.

24 une cytopenia is a frequent manifestation of primary immunodeficiencies.

25 horough evaluation for monogenic defects and primary immunodeficiencies.

26 estone in understanding the genetic basis of primary immunodeficiencies.

27 ects in the PI3K-triggered pathway can cause primary immunodeficiencies.

28 ciated with infancy, AIDS, and IL-17-related primary immunodeficiencies.

29 responses and the characterization of human primary immunodeficiencies.

30 e combined immunodeficiency (SCID) and other primary immunodeficiencies.

31 y autoimmune diseases and even in those with primary immunodeficiencies.

32 homas, as the first manifestation of several primary immunodeficiencies.

33 e mechanisms of autoimmunity associated with primary immunodeficiencies.

34 senting symptoms and clinical course of many primary immunodeficiencies.

35 irus infection in hospitalized children with primary immunodeficiencies.

36 to analyse exome data from 24 patients with primary immunodeficiencies.

37 ences of norovirus shedding in patients with primary immunodeficiencies.

38 Stem-cell transplantation can cure primary immunodeficiencies.

39 that Xrcc2 defects could underlie some human primary immunodeficiencies.

40 logeneic transplantation in the treatment of primary immunodeficiencies.

41 manipulation strategies among children with primary immunodeficiencies.

42 2.7%) was similar to that of admissions with primary immunodeficiency (19.4%; p = 0.41) but significa

43 Primary immunodeficiencies affecting the function of neu

44 Patients with primary immunodeficiencies affecting the NK and/or T cel

45 rs, new concepts of the relationship between primary immunodeficiencies and autoimmunity have develop

46 mechanisms have recently been found to link primary immunodeficiencies and autoimmunity, including i

47 ogenic disorders of the blood system such as primary immunodeficiencies and beta-thalassaemia.

48 d NK cell deficiency, which is unusual among primary immunodeficiencies and bone marrow failures, was

49 d molecular features that characterize these primary immunodeficiencies and discuss therapy options.

50 more than 265 genes in which mutations cause primary immunodeficiencies and rare forms of severe infl

51 We focused on genes associated with primary immunodeficiencies and related pathways.

52 ulome is enriched for genes mutated in human primary immunodeficiencies and with loci associated with

53 ptive and innate immune responses, including primary immunodeficiency and autoimmune diseases.

54 cing (WES) to detect an underlying monogenic primary immunodeficiency and potentially target therapy

55 -function mutations in RIPK1 presenting with primary immunodeficiency and/or intestinal inflammation.

56 ociated VDPVs (iVDPVs) from individuals with primary immunodeficiencies, and (3) ambiguous VDPVs (aVD

57 ted with genetically altered HSCs, including primary immunodeficiencies, and should facilitate the st

58 urbations in the LFA-1-C3-axis contribute to primary immunodeficiency, and identifies intracellular C

59 CARD11 gene result in at least four types of primary immunodeficiency, and somatic CARD11 gain-of-fun

60 Primary immunodeficiencies are a rare group of inborn di

61 Primary immunodeficiencies are often monogenic disorders

62 Although primary immunodeficiencies are quite rare in incidence,

63 Syndromic primary immunodeficiencies are rare genetic disorders th

64 n, and monogenic defects in genes related to primary immunodeficiencies are responsible for the disea

65 n large cohorts of patients transplanted for primary immunodeficiency are lacking.

66 IBD might mask an underlying primary immunodeficiency, as illustrated here with IL-21

67 uding increased homeostatic proliferation in primary immunodeficiencies associated with lymphopenia a

68 Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency associated with an increased su

69 Wiskott-Aldrich syndrome is a rare primary immunodeficiency associated with severe microthr

70 encies of MHC complex class I or II are rare primary immunodeficiencies, both of which are inherited

71 isms underlying EBV-induced disease in these primary immunodeficiencies but also identified molecules

72 y improve humoral immunity in the setting of primary immunodeficiencies but also temper their dysregu

73 y deficiencies (PADs) are the most prevalent primary immunodeficiencies, but their B-cell defects and

74 The realization that primary immunodeficiencies can also impair negative regu

75 ute to disease pathogenesis in patients with primary immunodeficiencies caused by mutations in compon

76 from chronic granulomatous disease (CGD), a primary immunodeficiency caused by a defect in the nicot

77 a rare form of autosomal recessive combined primary immunodeficiency caused by a enzyme defect leadi

78 tt-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency caused by absence of Wiskott-Al

79 Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defective production

80 and myelokathexis (WHIM) syndrome is a rare primary immunodeficiency caused by gain-of-function muta

81 iNKT are reduced in the primary immunodeficiency caused by mutations in the X-li

82 CD40 ligand (CD40L) deficiency, an X-linked primary immunodeficiency, causes recurrent sinopulmonary

83 ed through the National Reference Center for Primary Immunodeficiencies (CEREDIH) registry.

84 at the French National Reference Center for Primary Immunodeficiencies (CEREDIH) were retrospectivel

85 ndrome is a rare, life-threatening, X-linked primary immunodeficiency characterised by microthrombocy

86 recombination (Ig-CSR) deficiencies are rare primary immunodeficiencies characterized by defective sw

87 The hyper-IgE syndromes (HIES) are primary immunodeficiencies characterized by eczema, sino

88 f humans with monogenic mutations that cause primary immunodeficiencies characterized by impaired hum

89 witch recombination defects (CSR-D) are rare primary immunodeficiencies characterized by impaired pro

90 FOXN1 deficiency is a primary immunodeficiency characterized by athymia, alope

91 cause chronic granulomatous disease (CGD), a primary immunodeficiency characterized by dysfunctional

92 tions in human IL-2Rgammac result in SCID, a primary immunodeficiency characterized by greatly reduce

93 milial hemophagocytic lymphohistiocytosis, a primary immunodeficiency characterized by impaired lytic

94 hematopoietic cells, cause WAS, an X-linked primary immunodeficiency characterized by recurrent infe

95 f-function (GOF) mutations in PIK3CD cause a primary immunodeficiency characterized by recurrent resp

96 Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by serious infect

97 Omenn syndrome (OS) is an atypical primary immunodeficiency characterized by severe autoimm

98 ptibility to mycobacterial disease is a rare primary immunodeficiency characterized by severe infecti

99 DiGeorge syndrome (DGS) is a primary immunodeficiency characterized by various degree

100 nts with mutations in MAGT1 were linked to a primary immunodeficiency, characterized by chronic EBV i

101 n cause of infection in individuals with the primary immunodeficiency chronic granulomatous disease (

102 This study identifies a novel primary immunodeficiency, clarifying the contribution of

103 Primary immunodeficiencies comprise many diseases caused

104 (CARD9) deficiency is an autosomal recessive primary immunodeficiency conferring human susceptibility

105 Primary immunodeficiencies consist to a large extent of

106 ur hundred genes and regions associated with primary immunodeficiency, covering approximately 6500 co

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

108 The field of primary immunodeficiency disease (PIDD) has expanded rem

109 Activated PI3K Delta Syndrome (APDS) is a primary immunodeficiency disease caused by activating mu

110 y in Japan is reaching out regionally to the primary immunodeficiency disease community and internati

111 We present PIDO, the primary immunodeficiency disease ontology.

112 here is urgent need for the establishment of primary immunodeficiency disease registries, stem cell t

113 n infantile onset of the autosomal recessive primary immunodeficiency disease veno-occlusive disease

114 ommon variable immune deficiency (CVID) is a primary immunodeficiency disease, characterized by hypog

115 The most profound primary immunodeficiency disease, severe combined immuno

116 r hematopoietic stem cell transplantation in primary immunodeficiency disease.

117 pecific incidence of cancer in subjects with primary immunodeficiency diseases (PIDD) enrolled in the

118 Primary immunodeficiency diseases (PIDDs) are clinically

119 Primary immunodeficiency diseases (PIDDs) are inherited

120 ideration of many patients suspected to have primary immunodeficiency diseases (PIDDs) is the applica

121 REVIEW: Neutropenia is a feature of several primary immunodeficiency diseases (PIDDs).

122 Primary immunodeficiency diseases (PIDs) are characteriz

123 Primary immunodeficiency diseases (PIDs) are Mendelian c

124 been reported occasionally in patients with primary immunodeficiency diseases (PIDs) since the early

125 Analyses of other genes mutated in primary immunodeficiency diseases (PIDs) where reversion

126 The rapid increases in newly recognized primary immunodeficiency diseases (PIDs), including thei

127 hniques are an essential diagnostic tool for primary immunodeficiency diseases (PIDs).

128 d the genetic characterization of many human primary immunodeficiency diseases (PIDs).

129 he cornerstone of treatment in patients with primary immunodeficiency diseases affecting the humoral

130 s progress in the study of rare variants and primary immunodeficiency diseases arising from whole-exo

131 ciency disorders (CVID) represent a group of primary immunodeficiency diseases characterized by hypog

132 ican Academy of Allergy, Asthma & Immunology Primary Immunodeficiency Diseases Committee established

133 Primary immunodeficiency diseases comprise a group of he

134 ic studies implicate STATs in autoimmune and primary immunodeficiency diseases in humans.

135 Identification of the genetic causes of primary immunodeficiency diseases revealed that Th17 cel

136 Physicians caring for patients with primary immunodeficiency diseases were identified throug

137 side other symptoms in patients with various primary immunodeficiency diseases with diverse genetic d

138 Children with primary immunodeficiency diseases, particularly those le

139 t studies to determine optimal therapies for primary immunodeficiency diseases.

140 that study the treatment of rare and severe primary immunodeficiency diseases.

141 pplications for the domain of immunology and primary immunodeficiency diseases.

142 is and management of patients with suspected primary immunodeficiency diseases.

143 nostic evaluation of patients with suspected primary immunodeficiency diseases.

144 ws for emergence of many autosomal recessive primary immunodeficiency diseases.

145 Wiskott-Aldrich syndrome (WAS), an X-linked primary immunodeficiency disorder (PID) resulting from t

146 These results provide evidence of a primary immunodeficiency disorder associated with organ-

147 agocytic lymphohistiocytosis (HLH) is a rare primary immunodeficiency disorder characterized by defec

148 ctions, and myelokathexis (WHIM) syndrome, a primary immunodeficiency disorder characterized by neutr

149 bulinemia, infections, and myelokathexis), a primary immunodeficiency disorder involving panleukopeni

150 hronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytes resultin

151 e now identified a cohort of patients with a primary immunodeficiency disorder whose B cells oppose E

152 inase 1 (MST1) loss of function with a human primary immunodeficiency disorder, suggesting that MST1

153 sociated panuveitis, and another patient had primary immunodeficiency disorder.

154 Caregivers of children with primary immunodeficiency disorders (PIDs) experience sig

155 Primary immunodeficiency disorders (PIDs) represent a ra

156 nd manifest earlier in life in patients with primary immunodeficiency disorders (PIDs) than in the ge

157 made in the past decade in treating several primary immunodeficiency disorders (PIDs) with gene ther

158 used in the transplantation of patients with primary immunodeficiency disorders (PIDs), but there are

159 t has been implicated in the pathogenesis of primary immunodeficiency disorders and cancer.

160 Recent research on primary immunodeficiency disorders and the identificatio

161 vity Immunoglobulin E mediated syndromes are primary immunodeficiency disorders associated with sensi

162 Primary immunodeficiency disorders enable identification

163 asma and have been used for the treatment of primary immunodeficiency disorders for more than 25 year

164 Previous reports about primary immunodeficiency disorders have shown variations

165 discuss the usage of VSTs for patients with primary immunodeficiency disorders in clinical trials, a

166 In addition, other types of primary immunodeficiency disorders might be associated w

167 eatening in patients with moderate to severe primary immunodeficiency disorders.

168 tream signaling effectors resulting in known primary immunodeficiency disorders.

169 nts with clinical and laboratory evidence of primary immunodeficiency do not have a gene specific dia

170 HIES are primary immunodeficiencies due to monogenetic defects su

171 Hermansky-Pudlak syndrome type 2 (HPS2) is a primary immunodeficiency due to adaptor protein-3 (AP-3)

172 In contrast to primary immunodeficiencies, fundamental immunodeficiency

173 s discovered in all known IBD-associated and primary immunodeficiency genes in both siblings.

174 Hematologic malignancy and primary immunodeficiency had greater risk for mortality

175 methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic

176 ifferent haematological disorders (including primary immunodeficiencies, haemoglobinopathies and meta

177 dentification of the molecular etiologies of primary immunodeficiencies has led to important insights

178 The study of primary immunodeficiencies has provided opportunities to

179 Individuals with these primary immunodeficiencies have fewer immunoglobulin M (

180 Monogenic disorders leading to primary immunodeficiency have fascinated scientists and

181 em cell transplantation and gene therapy for primary immunodeficiency have had relative success; the

182 CH2 mutations that cause Mendelian monogenic primary immunodeficiency have not previously been identi

183 admissions with underlying nonmalignant non-primary immunodeficiency hematologic disease (15.4%; p =

184 re more than 180 different genetic causes of primary immunodeficiencies identified to date.

185 import receptor TfR1 as the cause of a human primary immunodeficiency, illuminating the importance of

186 For several primary immunodeficiencies, improved outcomes have been

187 containing and centralizing knowledge about primary immunodeficiencies in both a human- and computer

188 nherited conditions have been clustered with primary immunodeficiencies in the latest practice parame

189 We sought to identify the cause of the primary immunodeficiency in 2 young adult siblings with

190 sorder (CVID) is the most common symptomatic primary immunodeficiency in adults, characterized by B-c

191 catalytic subunit (POLD1) as the cause of a primary immunodeficiency in an extended kindred.

192 bulin A deficiency (IgAD) is the most common primary immunodeficiency in Europeans.

193 dmitted to the national reference center for primary immunodeficiency in France between 2006 and 2010

194 Progress in the treatment of primary immunodeficiencies included increased success wi

195 unction may prove useful in the diagnosis of primary immunodeficiencies including familial hemophagoc

196 ce was investigated in patients with several primary immunodeficiencies, including common variable im

197 receded by liver transplant in patients with primary immunodeficiencies, including the role of prolon

198 overies in this field provided insights into primary immunodeficiencies, inherited autoimmune and aut

199 Early detection of primary immunodeficiency is recognized as important for

200 as it pertains to the study and treatment of primary immunodeficiencies, is the content of this revie

201 TPP2 deficiency is the first primary immunodeficiency linking premature immunosenesce

202 We conclude that IFIH1 deficiency causes a primary immunodeficiency manifested in extreme susceptib

203 with chronic granulomatous disease (CGD), a primary immunodeficiency marked by a defect in NOX2, the

204 Thus, mutations associated with primary immunodeficiencies may cause disease by disrupti

205 mmon variable immunodeficiency (CVID) is the primary immunodeficiency most commonly encountered in cl

206 Physicians from major Italian Primary Immunodeficiency Network centers formulated and

207 of the COVID-19 pandemic, the United Kingdom Primary Immunodeficiency Network established a registry

208 ted disorders, physicians from major Italian Primary Immunodeficiency Network institutions focused on

209 decreased after establishment of the Italian Primary Immunodeficiency Network registry (84 months bef

210 nwide multicenter study based on the Italian Primary Immunodeficiency Network registry was establishe

211 Impaired immune functions leading to primary immunodeficiencies often correlate with paradoxi

212 patients with V(D)J recombination-defective primary immunodeficiencies or ataxia telangiectasia/Nijm

213 Eight patients had primary immunodeficiencies or blood disorders, while 4 o

214 downstream transcription factors that cause primary immunodeficiency or autoimmune conditions.

215 In five patients we detect a primary immunodeficiency or enteropathy, with clinical c

216 d the function of NOX in human patients with primary immunodeficiency other than chronic granulomatou

217 two subclones associated with cell cycle and primary immunodeficiency pathways identifies patients wi

218 late effects and enable SCT in virtually any primary immunodeficiency patient with a matched donor.

219 nodeficiency represents the largest group of primary immunodeficiency patients.

220 ed therapies for autoimmune complications in primary immunodeficiency patients.

221 In the present study, we report a primary immunodeficiency phenotype associated with MST1

222 mmunoglobulin (IGSC) replacement therapy for primary immunodeficiency (PI) is equally efficacious to

223 The role of primary immunodeficiencies (PID) in susceptibility to se

224 Primary immunodeficiency (PID) disorders are a heterogen

225 Primary immunodeficiency (PID) is characterized by recur

226 coronavirus 2 infection in individuals with primary immunodeficiency (PID) or symptomatic secondary

227 Primary immunodeficiency (PID) patients suffer recurrent

228 ched related donors (MMRDs) in patients with primary immunodeficiency (PID).

229 PURPOSE OF REVIEW: Primary immunodeficiencies (PIDs) are an often-devastati

230 Primary immunodeficiencies (PIDs) are inherited diseases

231 Some primary immunodeficiencies (PIDs) are known to confer pr

232 Primary Immunodeficiencies (PIDs) belong to the group of

233 The characterization of primary immunodeficiencies (PIDs) in human subjects is c

234 ber of contributions to our understanding of primary immunodeficiencies (PIDs) in pathogenesis, diagn

235 e past two decades of patients with specific primary immunodeficiencies (PIDs) including severe combi

236 Most children with primary immunodeficiencies (PIDs) now reach adulthood.

237 Primary immunodeficiencies (PIDs) represent exquisite mo

238 Primary immunodeficiencies (PIDs) that predispose to EBV

239 Genetic mutations cause primary immunodeficiencies (PIDs) that predispose to inf

240 We review the primary immunodeficiencies (PIDs) underlying an increasi

241 the 232 monogenic etiologies (21%) of human primary immunodeficiencies (PIDs) were initially reporte

242 leading fatal complication for patients with primary immunodeficiencies (PIDs) who require hematopoie

243 eatment for children with a wide spectrum of primary immunodeficiencies (PIDs), but outcome is heavil

244 The primary immunodeficiencies (PIDs), rare inherited diseas

245 d mortality in the majority of patients with primary immunodeficiencies (PIDs), the application of a

246 cytopenia and represent key features of many primary immunodeficiencies (PIDs).

247 range of defects that occur in actin-related primary immunodeficiencies (PIDs).

248 were mostly related to the expanding area of primary immunodeficiencies (PIDs).

249 of loci, including genes known to cause the primary immunodeficiencies (PIDs).

250 (HSCT) is used as a therapeutic approach for primary immunodeficiencies (PIDs).

251 with the most extreme cases being Mendelian primary immunodeficiencies (PIDs).

252 ed analysis of inflammatory disease GWAS and primary immunodeficiencies point to shared proteins and

253 roenteric virus contamination in a pediatric primary immunodeficiency (PPI) ward and a general pediat

254 ted families of different ethnicities with a primary immunodeficiency, predominantly manifesting as s

255 stem cells were developed from patients with primary immunodeficiencies, providing a virtually unlimi

256 the RAG1/2 genes result in various forms of primary immunodeficiency, ranging from T(-)B(-) severe c

257 Between 2006 and 2017, 147 patients with primary immunodeficiencies received 155 mismatched graft

258 IL-21 and IL-21R deficiencies cause severe, primary immunodeficiency reminiscent of common variable

259 Primary immunodeficiencies represent model diseases for

260 Human primary immunodeficiencies resulting from monogenic muta

261 Chronic granulomatous disease (CGD) is a primary immunodeficiency resulting in life-threatening i

262 ngitudinal study of 878 patients with likely primary immunodeficiency sequenced between 2010 and 2020

263 f various infectious arthritides in selected primary immunodeficiency states.

264 Netherton syndrome has been proposed to be a primary immunodeficiency syndrome because of the high fr

265 cently shown that DOCK8, a gene mutated in a primary immunodeficiency syndrome, is involved in NK cel

266 aling pathway as a genetic etiology for this primary immunodeficiency syndrome.

267 STK4 deficiency is a novel human primary immunodeficiency syndrome.

268 The link between autoimmune diseases and primary immunodeficiency syndromes has been increasingly

269 to the limelight because it can be linked to primary immunodeficiency syndromes with autoimmunity.

270 Primary immunodeficiencies that affect the innate immune

271 , we report two sibling pairs with syndromic primary immunodeficiencies that exceptionally presented

272 Some individuals may have primary immunodeficiencies that predispose to severe inf

273 ezrin-radixin-moesin protein mutation and a primary immunodeficiency that could be referred to as X-

274 We conclude that XIAP deficiency is a unique primary immunodeficiency that is more appropriately clas

275 arameter for the diagnosis and management of primary immunodeficiency." This is a complete and compre

276 ions in 1 of 9 genes known to be involved in primary immunodeficiencies (TNFRSF6, CTLA4, STAT3, PIK3C

277 rameters for the diagnosis and management of primary immunodeficiencies to guide the clinician in the

278 This review focuses on recently identified primary immunodeficiencies to illustrate the strategies,

279 report that murine astrovirus can complement primary immunodeficiency to protect against murine norov

280 At the annual meeting of the Primary Immunodeficiency Treatment Consortium held in Bo

281 Patients with primary immunodeficiencies undergoing allogeneic hematop

282 and in environmental swabs from a pediatric primary immunodeficiency unit in London, United Kingdom,

283 characterization of genetic defects causing primary immunodeficiencies was essential in understandin

284 man with MKL1 deficiency, leading to a novel primary immunodeficiency, was identified.

285 ng patients with genetically uncharacterized primary immunodeficiencies, we detected 2 novel nonsense

286 ile is not observed in a wide range of other primary immunodeficiencies, we hypothesized that recurre

287 Selected primary immunodeficiencies were chosen, the genetic defe

288 munologic mechanisms and clinical studies of primary immunodeficiencies were most prevalent in 2011.

289 s and managing the risks of individuals with primary immunodeficiencies who can excrete vaccine-deriv

290 We retrospectively studied 502 children with primary immunodeficiency who were transplanted at our ce

291 ents underwent stem-cell transplantation for primary immunodeficiencies with an MIC regimen consistin

292 ) diseases resulting in loss of IgG; and (d) primary immunodeficiencies with potential mechanistic si

293 to assist in the diagnosis of patients with primary immunodeficiencies with V(D)J recombination and

294 ed reticulate pigmentary disorder (XLPDR), a primary immunodeficiency with autoinflammatory features.

295 lic mutations in the ITK gene cause a T-cell primary immunodeficiency with Epstein-Barr virus (EBV)-l

296 X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency with high morbidity and mortali

297 r findings define a new clinical entity of a primary immunodeficiency with increased susceptibility t

298 iskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency with severe platelet abnormalit

299 cy (SCID) represents the most lethal form of primary immunodeficiency, with mortality rates of greate

300 Patients with the primary immunodeficiency X-linked lymphoproliferative di