ライフサイエンスコーパス: HLH

1 HLH can also occur in patients with underlying rheumatol

2 HLH is associated with mutations in lymphocyte cytolytic

3 HLH is difficult to diagnose and can be part of inflamma

4 HLH occurs as both acquired and familial hemophagocytic

5 HLH proteins also regulate circadian clocks, protect aga

6 HLH proteins deposit or erase epigenetic marks, activate

7 HLH proteins orchestrate lineage specification, commitme

8 HLH-30 also upregulates MML-1 upon germline removal.

9 HLH-30 was activated shortly after Staphylococcus aureus

10 bditis elegans E-protein helix-loop-helix-2 (HLH-2) functions as a homodimer in directing development

11 lfilling >=4 and 7 of 9 (78%) fulfilling >=5 HLH-2004 diagnostic criteria died.

12 occurrence of systemic reactivations (>/=5/8 HLH criteria), partial systemic flares (<5 criteria and

13 uronal differentiation and identified ID1, a HLH inhibitor of premature neurogenesis, as a target.

14 malignant, or metabolic conditions (acquired HLH).

15 Additionally, HLH can develop in patients during infections or maligna

16 Unlike pediatric HLH, adult HLH is rarely driven by germline genetic variants.

17 ient mice still developed the aforementioned HLH-like symptoms.

18 Although HLH is well described in the pediatric population, less

19 wenty-one of 180 (12%) had HLH defined as an HLH probability >=70% according to histo score (HScore);

20 riptionally up-regulated in starvation in an HLH-30-dependent manner, also demonstrated increased mor

21 dren from the same center presenting with an HLH-like illness after onset of adenovirus type 7 infect

22 Ectopic expression of HLH-2 and HLH-3 together promoted expression of neuronal features

23 MML-1/MXL-2 and HLH-30 transcriptomes show both shared and preferential

24 0]; GFP-tagged endogenous LIN-12, LAG-2, and HLH-2, a conserved transcription factor that orchestrate

25 a), partial systemic flares (<5 criteria and HLH-directed treatment), isolated central nervous system

26 erforin in anti-CD19 CAR T cell efficacy and HLH-like toxicities in a syngeneic murine model.

27 onfirms the presence of hemophagocytosis and HLH pathology.

28 ntiation between secondary post-HSCT HLH and HLH related to the genetic defect difficult.

29 ficantly reducing tissue immunopathology and HLH disease manifestations in vivo.

30 estimated incidence rates for malignancy and HLH as events/1000 patient-years of follow-up.

31 unadjusted incidence rates of malignancy and HLH in pediatric patients with IBD exposed to infliximab

32 Murine models of MAS and HLH illustrate that interferon-gamma (IFNgamma) is the d

33 yshematopoiesis, autoinflammation, rash, and HLH.

34 with LONG HYPOCOTYL IN FAR-RED1 (HFR1), a (b)HLH protein that inhibits shade avoidance.

35 Another (b)HLH protein, KIDARI (KDR), which is non-DNA-binding, was

36 The fuzzy tail beyond the structured b-HLH/ZIP domain (~165 residues) also contributes to the s

37 des the ubiquitous adapter Ldb1 along with b-HLH and/or GATA family transcription factors; however, d

38 protein that inhibits the function of basic HLH E protein transcription factors in lymphoid cells, h

39 riven down-regulation can target other basic HLH (bHLH) dimers as well.

40 ID3, decreased levels of the proneural basic HLH (bHLH) transcriptional regulators TCF4 and NEUROD6 a

41 f1(-/-) and Rab27a(-/-) mice with full-blown HLH syndrome were treated with a clinically relevant dos

42 Clinical manifestations of both HLH subtypes are often precipitated by a viral infection

43 highly conserved repressor of ATGL-1 called HLH-11/AP4.

44 ce from the fatal outcome that characterizes HLH-like disease and was also sufficient to reduce HLH-l

45 of macrophage overactivation characterizing HLH in 2 murine models.

46 should be considered for addition to current HLH criteria.

47 endent and -independent mechanisms to dampen HLH by targeting the deleterious effects of T cells and

48 , (3) assess mortality rate in SD and dengue-HLH, and (4) identify mortality-associated risk factors

49 tiorgan failure at risk of developing dengue-HLH.

50 Be observant of dengue-HLH due to its high mortality.

51 ere to (1) determine the frequency of dengue-HLH in SD, (2) describe clinical features of dengue-HLH,

52 SD, (2) describe clinical features of dengue-HLH, (3) assess mortality rate in SD and dengue-HLH, and

53 nce alignment and variant filtering detected HLH gene mutations and potential disease-causing variant

54 ancy and all 5 of the patients who developed HLH had been exposed to thiopurines; 10 patients with ma

55 rus infection during 2018-2019 who developed HLH or HLH-like illness.

56 a single patient was reported who developed HLH.

57 s did indeed increase the risk of developing HLH immunopathology after lymphocytic choriomeningitis v

58 f bHLH-encoding genes-and therefore distinct HLH-2:bHLH dimers-and formulate a "bHLH code" hypothesis

59 ore who fulfilled at least five of the eight HLH-2004 criteria for hemophagocytic lymphohistiocytosis

60 s can functionally substitute for C. elegans HLH-2 in regulating AC development and also display dime

61 as their ortholog in Caenorhabditis elegans HLH-30, play an important role in mediating cellular res

62 ology but also is effective against existing HLH, cytotoxicity-impaired Prf1(-/-) and Rab27a(-/-) mic

63 observed in untreated patients experiencing HLH flares.

64 h that the alpha cell whose parent expressed HLH-2 first is biased toward the VU fate.

65 milial hemophagocytic lymphohistiocytosis (F-HLH) and Griscelli syndrome type 2 (GS) are life-threate

66 (GS) and PRF1, UNC13D, STX11, and STXBP2 (F-HLH).

67 helix-loop-helix (bHLH) transcription factor HLH-2, the sole ortholog of the E proteins mammalian E2A

68 iogenesis and autophagy transcription factor HLH-30/TFEB.

69 basic helix-loop-helix transcription factor, HLH-30.

70 Familial HLH is associated with genetic cytotoxic impairment and

71 tions affecting cytotoxic function (familial HLH) or be secondary to infectious, rheumatologic, malig

72 ation include pathogenic changes in familial HLH genes (PRF1, UNC13D, STXBP2, and STX11), several gra

73 -/- mice develop prolonged viremia and fatal HLH.

74 converted nonfatal disease course into fatal HLH, identifying T-cell exhaustion as an important facto

75 using risk scoring methodology designed for HLH.

76 Genes encoding for HLH proteins arose in unicellular organisms >600 million

77 luding blinatumomab, should be monitored for HLH, and cytokine-directed therapy may be considered in

78 A genetic predisposition for HLH was not identified in any patient.

79 st performance in 1614 patients referred for HLH evaluation.

80 and linoleic acid bypass the requirement for HLH-30 in coupling lysosome nutrient sensing to survival

81 ariety of conditions and is not specific for HLH in adults.

82 on, marked hyperferritinemia is specific for HLH.

83 Frontline therapy for HLH consists of the glucocorticoid dexamethasone (DEX) a

84 omerase II, is the mainstay of treatment for HLH, although its therapeutic mechanism remains unknown.

85 lucose was sufficient to rescue animals from HLH.

86 r the wide disease spectrum that ranges from HLH secondary to severe infection to FHL.

87 iption 1 activation and led to recovery from HLH manifestations in both murine models.

88 totoxicity testing for screening for genetic HLH and should be considered for addition to current HLH

89 Twenty-one of 180 (12%) had HLH defined as an HLH probability >=70% according to his

90 ein, occurring through the Helix-Loop-Helix (HLH) and PER-ARNT-SIM (PAS) domains, is needed to conver

91 We demonstrate that the helix-loop-helix (HLH) protein Extramacrochaetae (Emc) regulates Ci(155) l

92 Id1, a helix-loop-helix (HLH) protein that inhibits the function of basic HLH E p

93 We demonstrate that the helix-loop-helix (HLH) protein, HEB, directly associates with the Polycomb

94 Helix-loop-helix (HLH) proteins are dimeric transcription factors that con

95 unction of the Id3 and E2A helix-loop-helix (HLH) proteins.

96 eurogenin-3 (NEUROG3) is a helix-loop-helix (HLH) transcription factor involved in the production of

97 tae (emc), which encodes a helix-loop-helix (HLH) transcription factor.

98 , we identify a network of helix-loop-helix (HLH) transcriptional regulators controlled by MYT1L, as

99 ion of a common downstream helix-loop-helix (HLH)/bHLH network, thus forming an incoherent feed-forwa

100 dy, 103 patients transplanted for hereditary HLH (2000-2013) and DC permanently or transiently <75% (

101 differentiation between secondary post-HSCT HLH and HLH related to the genetic defect difficult.

102 ate that recapitulates many aspects of human HLH.

103 From this screen, we identified HLH-3, the C. elegans homolog of a mammalian proneural p

104 In HLH patients, severe and transient lymphopenia, activate

105 tinib was exerting its beneficial effects in HLH by inhibiting IFN-gamma signaling or by targeting si

106 Notably, many cytokines that are elevated in HLH activate the JAK/STAT pathway, and the JAK1/2 inhibi

107 be associated with heterozygous mutations in HLH genes.

108 ubly or triply heterozygous for mutations in HLH-associated genes, those coding for perforin, Rab27a,

109 kine-driven hyperinflammation that occurs in HLH.

110 f cytokines, including those overproduced in HLH.

111 tion of the only cysteine residue present in HLH-30 (C284) significantly reduced its activity, result

112 ht similarly contribute to DEX resistance in HLH, and that RUX treatment would overcome this phenomen

113 t adenovirus 7 infection alone can result in HLH.

114 tor for determination of disease severity in HLH.

115 ibition using a model of primary (inherited) HLH in which perforin-deficient (Prf1(--)) mice are infe

116 udies reveal how an extensive interdependent HLH transcription factor network distributes responsibil

117 motes the nuclear localization of intestinal HLH-30/TFEB, a key pro-longevity regulator.

118 referential outputs including MDL-1/MAD-like HLH factor required for longevity.

119 Here we identify a Myc-like HLH transcription factor network comprised of Mondo/Max-

120 ial role of NK-cell cytotoxicity in limiting HLH-like immunopathology, highlighting the important rol

121 condary haemophagocytic lymphohistiocytosis (HLH) both clinically and based on molecular inflammatory

122 Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-t

123 istic of hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS).

124 SCT) for hemophagocytic lymphohistiocytosis (HLH) at the cost of more frequent mixed chimerism.

125 Primary hemophagocytic lymphohistiocytosis (HLH) can be caused by biallelic mutations in PRF1, encod

126 Hemophagocytic lymphohistiocytosis (HLH) comprises an emerging spectrum of inherited and non

127 Hemophagocytic lymphohistiocytosis (HLH) is a devastating disorder of uncontrolled immune ac

128 Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune dysregula

129 Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory condition.

130 Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory disease.

131 Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immunological disorder that i

132 Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome that often occurs in

133 Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome, characterized by se

134 Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, heterogeneous, hyperinflammm

135 Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease affecting mostly

136 Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of uncontrolled immune activatio

137 lt-onset hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease of immune hyper

138 Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory condition driven by excess

139 Hemophagocytic lymphohistiocytosis (HLH) is a syndrome describing patients with severe syste

140 Hemophagocytic lymphohistiocytosis (HLH) is an inborn disorder of immune regulation caused b

141 Hemophagocytic lymphohistiocytosis (HLH) is an often-fatal disorder characterized by the ove

142 Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to ina

143 primary hemophagocytic lymphohistiocytosis (HLH) occurs in infancy resulting from homozygous mutatio

144 sembling hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) occur after

145 primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent, or progressive disease

146 Hemophagocytic lymphohistiocytosis (HLH), a disease often associated with inherited defects

147 cipitate hemophagocytic lymphohistiocytosis (HLH), a life-threatening systemic inflammatory disorder.

148 arity to hemophagocytic lymphohistiocytosis (HLH), and some authors prefer the term secondary HLH to

149 odels of hemophagocytic lymphohistiocytosis (HLH), and the HLH-sibling macrophage activation syndrome

150 disorder hemophagocytic lymphohistiocytosis (HLH), characterized by uncontrolled CD8 T-cell and macro

151 underlie hemophagocytic lymphohistiocytosis (HLH), which requires hematopoietic cell transplantation

152 oallelic hemophagocytic lymphohistiocytosis (HLH)-associated mutations affecting codon 65 of STXPB2,

153 nts with hemophagocytic lymphohistiocytosis (HLH).

154 ncluding hemophagocytic lymphohistiocytosis (HLH).

155 reactive hemophagocytic lymphohistiocytosis (HLH).

156 ients to hemophagocytic lymphohistiocytosis (HLH).

157 bility to hemophagocytic lymphohistocytosis (HLH).

158 (H1N1) infection met 44% and 81% of modified HLH-2004 and MAS criteria, respectively.

159 d laboratory features of HLH, using modified HLH-2004 and macrophage activation syndrome (MAS) criter

160 carry a monoallelic mutation in one or more HLH-associated genes.

161 lizing antibody (alphaIFN-gamma) in 2 murine HLH models.

162 xolitinib (RUX) has shown efficacy in murine HLH models and humans with refractory disease.

163 stantially alleviated all symptoms of murine HLH and allowed prolonged survival.

164 th mutations that disrupt expression of MYB, HLH and/or WRKY transcription factors homologous to thos

165 showed that MUC1-C binds directly to the MYC HLH-LZ domain and identified a previously unrecognized M

166 is virus (LCMV) and secondary (noninherited) HLH in which C57BL/6 mice receive repeated injections of

167 Self-sperm maintenance of nuclear HLH-30/TFEB allows hermaphrodites to resist mating-induc

168 rvival with refeeding despite the absence of HLH-30.

169 HLH domains, and the elaborate activities of HLH proteins in multicellular life are discussed.

170 gulates nuclear localization and activity of HLH-30/TFEB, a convergent regulator of autophagy, lysoso

171 Our structure-function analysis of HLH-2 indicates that dimerization drives its degradation

172 LH-like disease, in whom multiple aspects of HLH pathology were observed in the absence of IFN-gamma

173 1-deficient patient with multiple aspects of HLH pathology, we used the mouse model of perforin (Prf1

174 We report the first case of HLH due to Bartonella henselae infection in a patient wi

175 Identifying the exact cause of HLH is crucial, as definitive treatment for primary dise

176 ough cytotoxic T lymphocyte (CTL) control of HLH development is well documented, the role for natural

177 oxicity can contribute to the development of HLH, we generated mice that were doubly or triply hetero

178 The diagnosis of HLH is based on a constellation of clinical and laborato

179 Here the evolution of HLH genes, the structures of HLH domains, and the elabor

180 Ectopic expression of HLH-2 and HLH-3 together promoted expression of neuronal

181 inical intervention based on the features of HLH in individual patients.

182 The hematologic features of HLH were completely dependent on IFN-gamma production, w

183 displayed the clinicopathologic features of HLH, as set forth in the Histiocyte Society diagnostic g

184 us, pearl mice developed all key features of HLH, linked to impaired virus control caused by a modera

185 yzed for clinical and laboratory features of HLH, using modified HLH-2004 and macrophage activation s

186 atients with a so-called "secondary" form of HLH, which develops in the aftermath of infection, autoi

187 Inherited forms of HLH are caused by biallelic mutations in several effecto

188 n often suffer from primary genetic forms of HLH, which can be triggered by infection.

189 rimary, and perhaps even secondary, forms of HLH.

190 ECATE (HEC) proteins, another small group of HLH proteins, antagonistically regulate PIFs to promote

191 Hundreds of HLH proteins have been identified with diverse functions

192 we demonstrate that the hypercytokinemia of HLH reduces the apoptotic potential of CD8 T cells leadi

193 ents are interrelated, because initiation of HLH-2 expression is linked to the birth of the parent ce

194 Loss of HLH-30 markedly impaired survival in starved larval worm

195 he clinical and laboratory manifestations of HLH, including weight loss, organomegaly, anemia, thromb

196 drome, resembling clinical manifestations of HLH.

197 ation and lessens inflammation in a model of HLH in which perforin-deficient (Prf1 (-/-)) mice are in

198 We used a murine model of HLH to examine how perforin controls immune activation,

199 Using ex vivo assays, a murine model of HLH, and primary patient samples, we demonstrate that th

200 We used a murine model of HLH, involving lymphocytic choriomeningitis virus infect

201 c events of each pathway in a mouse model of HLH.

202 nthesize the competing mechanistic models of HLH pathology into a dichotomous pathogenesis driven thr

203 of the JAK1/2 not only prevents the onset of HLH immunopathology but also is effective against existi

204 eage three generations earlier, and onset of HLH-2 expression, such that the alpha cell whose parent

205 al role for cytokines in the pathogenesis of HLH, we sought to examine whether the inhibition of JAK

206 Moreover, the high percentage of HLH gene mutations suggests they are risk factors for mo

207 Early recognition of HLH and B. henselae through liver biopsy and serological

208 hagocytes, which are findings reminiscent of HLH.

209 This is the first report of HLH in association with STAT2 deficiency.

210 In opposition to the protective role of HLH-30 and DAF-16/FOXO, TOR/LET-363 and the IIS-regulate

211 tical to prevent the catastrophic sequela of HLH.

212 t mice displayed a more complete spectrum of HLH, including splenomegaly, coagulopathy, and decreased

213 he evolution of HLH genes, the structures of HLH domains, and the elaborate activities of HLH protein

214 s that can be complicated by the syndrome of HLH.

215 characteristics, diagnosis, and treatment of HLH in adults.

216 tions to its broader use in the treatment of HLH.

217 xperience gained through treatment trials of HLH and MAS in childhood may inform study design for the

218 he critical protective effect of NK cells on HLH was independent of interferon-gamma secretion and ch

219 more common in individuals with adult-onset HLH and can contribute to the pathophysiology of this di

220 Using the adult-onset HLH mouse model in which repeated treatments of the TLR9

221 atory state, could contribute to adult-onset HLH.

222 ection during 2018-2019 who developed HLH or HLH-like illness.

223 t event for the development of malignancy or HLH in pediatric patients with IBD.

224 sociate with increased risk of malignancy or HLH in pediatric patients with IBD.

225 k of malignancy (0.46/1000 patient-years) or HLH (0.0/1000 patient-years) in patients exposed to IFX

226 e we show that the predicted TFEB orthologue HLH-30 regulates autophagy in Caenorhabditis elegans and

227 summarize current concepts in the pediatric HLH field as well as offer a practical diagnostic and tr

228 Unlike pediatric HLH, adult HLH is rarely driven by germline genetic vari

229 of donor chimerism (DC) required to prevent HLH reactivation in humans remains to be determined.

230 Primary HLH is caused by mutations in granule-mediated cytotoxic

231 Primary HLH occurs early in life as a result of monogenic bialle

232 link between perforin deficiency and primary HLH, we investigated the role of perforin in anti-CD19 C

233 ed to its central pathogenic role in primary HLH.

234 ill highlight the pathophysiology of primary HLH, the therapeutic rationale for use of IFN-gamma-targ

235 key pathogenic cytokine in models of primary HLH, were the highest.

236 t dissimilarity from mouse models of primary HLH.

237 Mating induces the agonist INS-8, promoting HLH-30 nuclear exit and subsequent death.

238 A prospective study is suggested on prompt HLH-directed therapy in SD patients with hyperinflammati

239 ts together with a second proneural protein, HLH-2, and in parallel to HLH-3 to promote I4 neurogenes

240 ke disease and was also sufficient to reduce HLH-like manifestations.

241 ly, PIF4 bound all direct and down-regulated HLH/bHLH targets of IBH1 and IBL1.

242 ed in terms of the severity of the resulting HLH manifestations.

243 Secondary HLH occurs mostly in adults secondary to infection, lymp

244 Secondary HLH presents after infancy and may be associated with he

245 ic distinction between primary and secondary HLH by contributing to HLH via a partial dominant-negati

246 e pathogenesis of virus-associated secondary HLH as opposed to its central pathogenic role in primary

247 n animal model of virus-associated secondary HLH by infecting immunocompetent wild-type mice with the

248 Others suffer from secondary HLH as a complication of infection, malignancy, or rheum

249 rinsic cytotoxicity dysfunction in secondary HLH patients compared with DCs and no predicted pathogen

250 lygenic model of the occurrence of secondary HLH.

251 , and some authors prefer the term secondary HLH to describe it.

252 ule-mediated cytotoxicity, whereas secondary HLH occurs, without a known genetic background, in a con

253 Adult patients with secondary HLH were prospectively studied ex vivo for total lymphoc

254 ytotoxicity in adult patients with secondary HLH.

255 6%) patients classified as having "sporadic" HLH, 43 had monoallelic mutations in one of the FHL-defi

256 We suggest that the clinical syndrome HLH generally results from the combined effects of an ex

257 f hemophagocytic lymphohistiocytic syndrome (HLH).

258 study, we identify a novel mechanism of TFEB/HLH-30 regulation through a cysteine-mediated redox swit

259 ges in redox balance with expression of TFEB/HLH-30 target genes.

260 l Caenorhabditis elegans, we discovered that HLH-30 (known as TFEB in mammals) is a key transcription

261 logies have been identified, the reason that HLH occurs in only a subset of individuals and how other

262 These results show that HLH-30 activation is critical for sustaining survival du

263 Although this observation suggests that HLH may have a polygenic mode of inheritance, the latter

264 The HLH protein Extramacrocheate (Emc), which forms heterodi

265 TOH1 is closely correlated with HEYL and the HLH inhibitory transcription factors ID1, ID2, and ID4.

266 hagocytic lymphohistiocytosis (HLH), and the HLH-sibling macrophage activation syndrome (MAS).

267 late CAR T cell expansion characterized the HLH-like syndromes occurring in the murine model and in

268 CD8(+) T cells could not inhibit or cure the HLH-like syndrome, highlighting a first dissimilarity fr

269 mples were collected and analyzed during the HLH episode.

270 a potential deterministic mechanism for the HLH-2 expression bias by showing that hlh-2 is required

271 68 patients were included in the HLH group and 34 each in the DC and HC groups.

272 aplastic lymphoma kinase, is upstream of the HLH regulatory protein, Id2a, and of the retinoblastoma

273 n IFN-gamma-dependent manner to reverse this HLH manifestation.

274 mpair lytic granule fusion and contribute to HLH.

275 d understudied cell type that contributes to HLH pathogenesis.

276 primary and secondary HLH by contributing to HLH via a partial dominant-negative effect.

277 nt, or progressive disease or intolerance to HLH therapy.

278 proneural protein, HLH-2, and in parallel to HLH-3 to promote I4 neurogenesis.

279 re found to have a genetic predisposition to HLH.

280 contribution of these lymphocyte subsets to HLH-like disease severity after lymphocytic choriomening

281 vity and mechanism of etoposide for treating HLH and found that it substantially alleviated all sympt

282 Thus, etoposide treats HLH by selectively eliminating pathologic, activated T c

283 In addition, a tripartite HLH/bHLH module feedback regulates PIFs and additional b

284 hepatosplenomegaly, and elevation of typical HLH biomarkers.

285 el provides a new paradigm for understanding HLH and, more broadly, the consequences of CD8(+) T-cell

286 It can be challenging to determine whether HLH is the result of an infectious pathogen alone or gen

287 fatal hyperinflammatory condition for which HLH-directed therapy (as etoposide and dexamethasone) ca

288 Classic genetic diseases in which HLH is a typical and common manifestation include pathog

289 ere are many other genetic diseases in which HLH is an infrequent complication of the disorder as opp

290 More and more, it is recognized that while HLH can be appropriately used as a broad summary diagnos

291 highly annotated cohort of older adults with HLH we found that CH was more prevalent than in control

292 Adenoviruses have been associated with HLH but molecular epidemiology data are lacking.

293 thus improve the outcomes for patients with HLH and related CSS.

294 IFN-gamma receptor 1-deficient patients with HLH-like disease, in whom multiple aspects of HLH pathol

295 to persistent inflammation in patients with HLH.

296 yzed a total of 500 unselected patients with HLH.

297 e-associated protein (SAP), may present with HLH.

298 We report two unrelated teenagers with HLH and an identical heterozygous RAB27A mutation (c.259

299 ected by the same underlying disease without HLH (disease controls [DCs]) and with healthy controls (

300 logics (malignancy: 1.12/1000 patient-years; HLH: 0.56/1000 patient-years).