ライフサイエンスコーパス: SLE

1 SLE 'variant-to-gene' maps also implicate genes with no

2 SLE patients with the DAP1 genotype have distinct autoan

3 SLE transcriptomic data from two cohorts were compared w

4 r and available for metabolic signature: (1) SLE and normal pregnancy outcome (Group 1, n = 21); (2)

5 large transcriptome profiling dataset of 148 SLE patients and 52 healthy individuals enabled the iden

6 mal pregnancy outcome (Group 1, n = 21); (2) SLE with APO (Group 2, n = 12); and (3) healthy pregnant

7 cing across the DAP1 genomic segment in 2032 SLE patients, and healthy controls, and discover a low-f

8 Here we found that 45% SLE patients had circulating T-cells strongly responding

9 nce Research Database was used to assemble a SLE cohort consisting of newly diagnosed SLE between 200

10 Accordingly, SLE LL37-specific T-cells promoted B-cell secretion of p

11 ug-induced gene expression signatures across SLE patients and to evaluate the potential for clinical

12 ed biomarkers of composite disease activity, SLE-associated antibodies, type I interferon (IFN), and

13 The integration of all SLE SNP-predicted genes into functional pathways reveale

14 LE who develop LN do so within 5 years of an SLE diagnosis and, in many cases, LN is the presenting m

15 esponses, leading to autoreactive B cell and SLE development.

16 providing a connection between circRNAs and SLE.

17 cells in promoting TLR7-driven AFC, GC, and SLE development whereas T1IFN signaling moderately contr

18 ression, such as filaggrin and loricrin, and SLE keratinocytes exhibited increased S. aureus-binding

19 evobrutinib in preclinical models of RA and SLE and characterized the relationship between BTK occup

20 r-complete disease inhibition in both RA and SLE mouse models.

21 In mouse models of RA and SLE, orally administered evobrutinib displayed robust ef

22 study participants into classes (FM, RA, and SLE) with no misclassifications (p < 0.05, and interclas

23 ven autoimmune AFC, GC and Tfh responses and SLE development are dependent on IFN-gamma signaling in

24 ensor TLR9 promotes anti-dsDNA responses and SLE-like disease in Dnase1l3(-/-) mice redundantly with

25 elop rapid anti-dsDNA antibody responses and SLE-like disease.

26 AFC) and germinal center (GC) responses, and SLE development has never been directly investigated.

27 owever, improvement is still needed, because SLE pregnancy risks remain high.

28 ex vivo human studies, the inhibitor blocked SLE serum-induced IRF5 activation and reversed basal IRF

29 Both SLE- and RA-IgG increased ROS generation and DNA externa

30 as not found in numerous tissues affected by SLE.

31 e a SLE cohort consisting of newly diagnosed SLE between 2000 and 2012.

32 o study associations between LDG enrichment, SLE manifestations, and treatment regimens.

33 D n = 200), 3) systemic lupus erythematosus (SLE) (n = 200, HD n = 67; neuro-SLE n = 49, HD n = 33),

34 s pathology in systemic lupus erythematosus (SLE) and can be tracked via IFN-inducible transcripts in

35 eases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), is increasingly reco

36 mmune diseases systemic lupus erythematosus (SLE) and Sjogren's syndrome affect nine times more women

37 ritis (OA), or systemic lupus erythematosus (SLE) and to identify metabolites associated with these d

38 Patients with systemic lupus erythematosus (SLE) are at increased risk for adverse pregnancy outcome

39 patients with systemic lupus erythematosus (SLE) arise as a consequence of defective antigen-specifi

40 Systemic lupus erythematosus (SLE) can directly affect various part of the ocular syst

41 Patients with systemic lupus erythematosus (SLE) display a complex blood transcriptome whose cellula

42 Patients with Systemic lupus erythematosus (SLE) experience various peripheral and central nervous s

43 Systemic lupus erythematosus (SLE) flares elicit progressive organ damage, leading to

44 Patients with systemic lupus erythematosus (SLE) frequently show symptoms of central nervous system

45 patients with systemic lupus erythematosus (SLE) has caused a profound sense of disappointment among

46 itis (RA), and systemic lupus erythematosus (SLE) increase susceptibility to destructive periodontal

47 Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease ch

48 Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which 70% of pat

49 Systemic lupus erythematosus (SLE) is a complex autoimmune disease with genetic and en

50 Systemic lupus erythematosus (SLE) is a devastating autoimmune disease in which hypera

51 Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with a promine

52 Systemic lupus erythematosus (SLE) is a multisystem, chronic autoimmune disease where

53 Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by

54 Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the loss

55 Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the prese

56 Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the prese

57 Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease characterized

58 Systemic lupus erythematosus (SLE) is characterized by the expansion of extrafollicula

59 Systemic lupus erythematosus (SLE) is defined by loss of B cell tolerance, resulting i

60 Systemic lupus erythematosus (SLE) is mediated by a chronic and dysregulated inflammat

61 Systemic lupus erythematosus (SLE) is mediated by autoreactive antibodies that damage

62 Systemic Lupus Erythematosus (SLE) is the prototype of autoimmune diseases, characteri

63 Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease.

64 ngly linked to systemic lupus erythematosus (SLE) pathogenesis.

65 Most systemic lupus erythematosus (SLE) patients are photosensitive and ultraviolet B light

66 d only 6.8% of systemic lupus erythematosus (SLE) sera.

67 nifestation of systemic lupus erythematosus (SLE) yet understanding of the underlying pathogenic mech

68 seases such as systemic lupus erythematosus (SLE)(1).

69 ly affected by systemic lupus erythematosus (SLE), a chronic, potentially debilitating autoimmune dis

70 seases such as systemic lupus erythematosus (SLE), a condition characterized by aberrant type I IFN s

71 with a risk of systemic lupus erythematosus (SLE), and mice lacking Irf5 are protected from lupus ons

72 development of systemic lupus erythematosus (SLE), but the underlying mechanisms are incompletely und

73 seases such as systemic lupus erythematosus (SLE), but the underlying mechanisms remain incompletely

74 pia, diabetes, systemic lupus erythematosus (SLE), greater deprivation (Townsend index), and Goldmann

75 ses, including systemic lupus erythematosus (SLE), is an increased prevalence in women.

76 In systemic lupus erythematosus (SLE), LL37 also triggers IFN-I in pDCs and is target of

77 terogeneity of systemic lupus erythematosus (SLE), long recognised by clinicians, is now challenging

78 In systemic lupus erythematosus (SLE), these antibodies bind Fc receptors on myeloid cell

79 nd severity of systemic lupus erythematosus (SLE), using renal disease as a proxy for severity.

80 ouse models of systemic lupus erythematosus (SLE), we dissect dietary effects on the gut microbiota a

81 ith a focus on systemic lupus erythematosus (SLE), with the relevant translational opportunities, exi

82 pathogenic in systemic lupus erythematosus (SLE), yet mechanisms of their development remain poorly

83 s recurrent in systemic lupus erythematosus (SLE), yet mechanisms that drive cutaneous inflammation i

84 nflammation in systemic lupus erythematosus (SLE).

85 ogenic role in systemic lupus erythematosus (SLE).

86 contribute to systemic lupus erythematosus (SLE).

87 immune disease systemic lupus erythematosus (SLE).

88 matory loop in systemic lupus erythematosus (SLE).

89 athogenesis of systemic lupus erythematosus (SLE).

90 in particular systemic lupus erythematosus (SLE).

91 immune disease systemic lupus erythematosus (SLE).

92 ritis (RA) and systemic lupus erythematosus (SLE).

93 ritis (RA) and systemic lupus erythematosus (SLE).

94 athogenesis in systemic lupus erythematosus (SLE).

95 seases such as systemic lupus erythematosus (SLE).

96 triggering of systemic lupus erythematosus (SLE).

97 patients with systemic lupus erythematosus (SLE; 15 with NPSLE) showed no antibodies against nativel

98 py approved for systemic lupus erythematous (SLE) in over 50 y.

99 Systemic lupus erythematous (SLE) is a heterogeneous autoimmune disease in which outc

100 eases, a significant proportion of estimated SLE heritability is not accounted for by common disease

101 In this large study examining SLE and non-SLE pregnancies over 18 years, in-hospital m

102 ction methodologies (solid-liquid extraction SLE and ultrasound-assisted extraction UAE) were tested

103 itis than in patients with active extrarenal SLE, inactive SLE, and other glomerular diseases, and co

104 Ps with P-values above 0.2 were inflated for SLE true positive signals.

105 vealed that IFNs are important mediators for SLE and CLE, but the mechanisms by which IFNs lead to di

106 ar DNA, but this inhibition was overcome for SLE-IgG when the endothelium was stimulated with TNF-alp

107 a(7), generates 7-fold variation in risk for SLE and 16-fold variation in risk for Sjogren's syndrome

108 sk for schizophrenia greatly reduce risk for SLE and Sjogren's syndrome.

109 C4B generated 14-fold variation in risk for SLE, 31-fold variation in risk for Sjogren's syndrome, a

110 et for development of novel therapeutics for SLE.

111 microarray data and RNA sequencing data from SLE keratinocytes identified repression of barrier gene

112 ing circRNA in PBMCs or T cells derived from SLE can alleviate the aberrant PKR activation cascade, t

113 activity was also observed in the sera from SLE patients compared with healthy people and disease co

114 Knee synovia from SLE, OA, and RA patients were analyzed for differentiall

115 Further, SLE keratinocytes exhibited increased binding to S. aure

116 multidisciplinary advances to enhance future SLE treatment.

117 gative (ANA-) healthy, ANA+ healthy, or have SLE using single cell mass cytometry, next-generation RN

118 The model recapitulates hallmarks of human SLE and can be used to identify contributions of differe

119 MpJ mouse, a well-established model of human SLE, develops elevated antinuclear Abs and immune comple

120 mbosis are well-recognized features of human SLE, the exact mechanisms underlying platelet activation

121 In SLE patients, CD4(+)CCR6(+)IL-7R(+)T cells were associat

122 mechanisms underlying platelet activation in SLE remain unknown.

123 A in nephritis and in platelet activation in SLE.

124 Tfh cells; thus, restoring P2X7 activity in SLE patients could selectively limit the progressive amp

125 X-linked genes exhibiting AE in SLE had an extensive overlap with genes known to escape

126 how these metabolic processes are altered in SLE.

127 ildly increased neurologic autoantibodies in SLE may be consistent with a broader loss of B cell tole

128 icate a role for anti-BC RNA autoimmunity in SLE and its neuropsychiatric manifestations.SIGNIFICANCE

129 However, whether LL37 activates T-cells in SLE and how the latter differ from psoriasis LL37-specif

130 imbalance across the entire X chromosome in SLE lymphocytes.

131 XIST-associated skewed AE on X chromosome in SLE.

132 allows for higher S. aureus colonization in SLE skin.

133 o keep autoreactive T cells under control in SLE patients, immunosuppressive regimens are used, which

134 prehensive efforts to address disparities in SLE severity should include policies that address issues

135 er, the molecular basis for sex disparity in SLE remains poorly understood.

136 n skin disease and systemic exacerbations in SLE remains elusive.

137 e organization in shaping gene expression in SLE.

138 The performance of GRS in SLE risk prediction was evaluated by receiver operating

139 while interferon alpha levels were higher in SLE (p < 0.0001), they lacked specificity for NPSLE.

140 n and reversed basal IRF5 hyperactivation in SLE immune cells.

141 s (T(FH) cells) have long been implicated in SLE pathogenesis.

142 localises with TLR7, a pathway implicated in SLE pathogenesis.

143 D6), in regulation of IFN-alpha induction in SLE patients.

144 hanisms that drive cutaneous inflammation in SLE are not well defined.

145 uld play a role in cutaneous inflammation in SLE.

146 ect the well-defined role for interferons in SLE and revealed pathways associated with tissue repair

147 nt determinants of the appearance of LDGs in SLE and have emphasized the likely role of LDGs in speci

148 ed abundant citrullinated LL37 (cit-LL37) in SLE tissues (skin and kidney) and observed very pronounc

149 o investigate core resting state networks in SLE patients with and without neuropsychiatric symptoms

150 XIST RNA was overexpressed in SLE patients.

151 door on targeting the type 1 IFN pathway in SLE may be premature and highlight the emerging question

152 ic neutrophil heterogeneity are prevalent in SLE and may promote immune dysregulation and prominent v

153 Selenomonas, Leptotrichia, and Prevotella in SLE.

154 We aimed to investigate how IFN responses in SLE keratinocytes contribute to development of CLE.

155 ction of type I IFNs plays a pivotal role in SLE, a major source of type I IFNs being the plasmacytoi

156 nd could play a prominent pathogenic role in SLE.

157 ch for biomarkers and therapeutic targets in SLE.

158 complex (MHC) locus, an association that in SLE and Sjogren's syndrome has long been thought to aris

159 Thus, in SLE, we identified LL37-specific T-cells with a distinct

160 xamine the role of X-linked transcription in SLE adaptive immune cells, we performed RNA-seq in T cel

161 atients with active extrarenal SLE, inactive SLE, and other glomerular diseases, and correlated with

162 complex (IC)-associated diseases, including SLE and rheumatoid arthritis, and following IgG Fcgamma

163 significantly associate with many individual SLE pathologies.

164 Within 10 years of an initial SLE diagnosis, 5-20% of patients with LN develop end-sta

165 this strategy will be effective in managing SLE in other organs remains unanswered.

166 ants in lupus-risk genes are present in most SLE patients and healthy controls.

167 CD40 is a central disease pathway in murine SLE.

168 ythematosus (SLE) (n = 200, HD n = 67; neuro-SLE n = 49, HD n = 33), and 4) a control cohort of neuro

169 ric SLE (nNP) as well as in neuropsychiatric SLE patients (NP).

170 opsychological tests in non-neuropsychiatric SLE (nNP) as well as in neuropsychiatric SLE patients (N

171 m (CNS) involvement, termed neuropsychiatric SLE (NPSLE).

172 In this large study examining SLE and non-SLE pregnancies over 18 years, in-hospital maternal mort

173 Type I IFNs are elevated in nonlesional SLE skin and promote inflammatory responses.

174 significant negative correlation with age of SLE onset (Pcohort1 = 1.76e-12; Pcohort2 = 0.00384).

175 or anti-nuclear antibodies characteristic of SLE.

176 ds)DNA antibodies that are characteristic of SLE.

177 nectivity scores revealed robust clusters of SLE patients identical to the clusters previously obtain

178 ty, but how IRF5 functions in the context of SLE disease progression remains unclear.

179 involvement of FcgammaRIIA in the course of SLE and platelet activation.

180 As the development of SLE involves subversion of normal B cell tolerance check

181 ble strategies to prevent the development of SLE.

182 mmune complexes would promote development of SLE.

183 manifestation resulting in the diagnosis of SLE.

184 ption profiles, supporting the dissection of SLE heterogeneity by genetic analysis.

185 ecific and trans-ancestry genetic drivers of SLE.

186 ected by the combination of two hallmarks of SLE: CXorf21 expression increases in a both an IFN-induc

187 the molecular and clinical heterogeneity of SLE from transcriptomics studies and detail their potent

188 a provide insights into the immunobiology of SLE and identify type III IFNs as important factors for

189 tic insights into the increased incidence of SLE in females.

190 between HCMV infection and the induction of SLE.

191 roved understanding of this manifestation of SLE might yield further options for managing this diseas

192 able to target this common manifestation of SLE.

193 nephritis along with other manifestations of SLE-like disease.

194 t cellular lineages in the manifestations of SLE.

195 We generated high-resolution spatial maps of SLE variant accessibility and gene connectivity in human

196 espond to ICs in any existing mouse model of SLE, we introduced the FcgammaRIIA (FCGR2A) transgene in

197 transgene into the NZB/NZWF1 mouse model of SLE.

198 ease in the Tlr7.1 transgenic mouse model of SLE.

199 However, prior studies in murine models of SLE using gene-targeted Cr2(-/-) mice, which lack both C

200 R7-induced and TLR7 overexpression models of SLE, we report in this study a previously unrecognized i

201 We then analyzed the polygenic nature of SLE statistically.

202 cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margin

203 osome is associated with the pathogenesis of SLE and may provide mechanistic insights into the increa

204 We critically examine the pipeline of SLE drugs, including past failures and their associated

205 ently that the best GRS in the prediction of SLE used SNPs associated at the level of P < 1e-05 in al

206 re, interrogated gene expression profiles of SLE synovium to gain insight into the nature of lupus ar

207 r function contributes to the progression of SLE.

208 ects of Tlr9 expression on the regulation of SLE pathogenesis.

209 f C4 alleles in men, women's greater risk of SLE and Sjogren's syndrome and men's greater vulnerabili

210 gene in a previous familial linkage study of SLE and rheumatoid arthritis, but the association has no

211 l enrichment of Lactobacillus in a subset of SLE patients.

212 ive therapies, a far better understanding of SLE pathogenesis as it relates to the array of clinical

213 est a fundamentally revised understanding of SLE: that it is a disease of aberrant B-cell differentia

214 ptomic effects of type I and type II IFNs on SLE versus control keratinocytes.

215 +) T cells from patients with juvenile-onset SLE share phenotypical features with CREMalpha-overexpre

216 of FM (n = 50), RA (n = 29), OA (n = 19), or SLE (n = 23).

217 , compared with patients with APS (21.8%) or SLE (28.6%) or normal controls (23.3%), and have mutatio

218 ed protein measurements from anti-dsDNA(pos) SLE blood samples and derived an IFN protein signature (

219 ith so-called 'active, autoantibody-positive SLE'.

220 The GRS predicts SLE in both European and Chinese populations and correla

221 signaling pathways to regulate TLR7-promoted SLE.

222 The inhibition of IRAK4 repressed SLE immune complex- and TLR7-mediated activation of huma

223 ene expression datasets from two large-scale SLE clinical trials to study associations between LDG en

224 equencing samples from 14 individuals (seven SLE and seven healthy controls) were analyzed to study t

225 In addition, the risk of several SLE related ophthalmic disorders, including episcleritis

226 to psoriatic Th17-cells, these LL37-specific SLE T-cells displayed a T-follicular helper-(T(FH))-like

227 very pronounced reactivity of LL37-specific SLE T-cells to cit-LL37, compared to native-LL37, which

228 f belimumab in 2011 was the first successful SLE drug in nearly six decades.

229 so implicate genes with no known role in TFH/SLE disease biology, including the kinases HIPK1 and MIN

230 patients with autoimmune diseases other than SLE (e.g., rheumatoid arthritis or multiple sclerosis) o

231 We found that SLE- and RA-IgG both bound human neutrophils but differe

232 These results suggest that SLE flares may arise from an overlapping spectrum of lym

233 Our results suggest strong links between the SLE phenotype and the underlying genome structure and un

234 ity and preliminary clinical response in the SLE cohort.

235 I IFN neutralisation with anifrolumab in the SLE phase IIb study, MUSE.

236 These data indicate the SLE-derived ICs activate neutrophils to release ROS and

237 patients from 3 independent cohorts into the SLE subsets and provide a clinically useful model to pre

238 e studies offer mechanistic insight into the SLE-associated regulatory architecture of the human geno

239 e groundwork for resolving the origin of the SLE transcriptional signatures and the disease heterogen

240 hine learning classifier able to predict the SLE subset for individual patients.

241 between pathologies and correlation with the SLE Disease Activity Index (SLEDAI) were used to identif

242 + European Americans that is absent in their SLE or even healthy ANA- counterparts, or among African

243 These SLE-associated changes could be replicated by IFN treatm

244 netic architecture and how it contributes to SLE remain poorly understood.

245 ous NETosis, but the contribution of LDGs to SLE pathogenesis remains unclear.

246 Susceptibility to SLE is multifactorial, with a combination of genetic and

247 ic modulators are strong candidates to treat SLE patients with nervous system dysfunction.

248 he use of several new approaches to treating SLE are discussed in this Review, including: fully human

249 not observed in RA and T1D patients, whereas SLE patients harbored such autoantibodies in rare cases

250 ral blood mononuclear cells from adults with SLE confirmed the expansion of similar subpopulations in

251 ation and redistribution are associated with SLE clinical endophenotypes, with genes of the interfero

252 ived RNA and DNA is strongly associated with SLE in patients and in mouse models, but the mechanism b

253 unctional haplotype strongly associated with SLE risk in multiple ethnicities.

254 ISGs) distinguished cells from children with SLE from healthy control cells.

255 lood mononuclear cells from 33 children with SLE with different degrees of disease activity and 11 ma

256 gulation patterns, which also correlate with SLE activity status.

257 by identifying proteins that correlate with SLE organ involvement and to evaluate established biomar

258 ssociation studies (GWAS) link >60 loci with SLE risk, but the causal variants and effector genes are

259 0 patients without SLE for each patient with SLE, based on frequency matching for sex, five-year age

260 s conducted in HV (n = 54) and patients with SLE (n = 12).

261 Patients with SLE (n = 521) exhibited a significantly higher prevalenc

262 s that are used in the care of patients with SLE affect cell metabolism, and the development of novel

263 phthalmologist visits in adult patients with SLE and to evaluate the risk of dry eye syndrome, catara

264 ession during disease, as many patients with SLE are ANA negative at screening despite previously tes

265 al plasma to identify pregnant patients with SLE at increased risk of APOs.

266 d in the peripheral blood from patients with SLE compared with that of healthy controls using flow cy

267 retinal vascular occlusion in patients with SLE deserves vigilance.

268 peripheral blood T cells from patients with SLE displayed induction of ROR-gammat phosphorylation an

269 parison to controls (n = 104), patients with SLE had antibodies that bound to a peptide representing

270 and ANA+ healthy individuals, patients with SLE of both races displayed T-cell expansion and elevate

271 ells from lupus-prone mice and patients with SLE undergo clonal proliferation and expansion in a self

272 sis of ophthalmic disorders of patients with SLE using population-based data.

273 n 3 different mouse models and patients with SLE was characterized by glomerular accumulation of patr

274 Most patients with SLE who develop LN do so within 5 years of an SLE diagno

275 and identifies a new subset of patients with SLE who have IFN activity.

276 in healthy volunteers (HV) and patients with SLE with active cutaneous disease as well as proof of bi

277 clinical support for treating patients with SLE with an IRF5 inhibitor.

278 ted with SRSF1 in T cells from patients with SLE, and SRSF1 overexpression rescued PTEN and suppresse

279 Of 82 patients with SLE, IFNPS was elevated for 89% of IFNGS-high patients (

280 In patients with SLE, IRF5 hyperactivation correlated with dsDNA titers.

281 In patients with SLE, levels of ICs are associated with platelet activati

282 from either healthy donors or patients with SLE.

283 ortance to improve outcomes in patients with SLE.

284 RAK4 might be a therapeutic in patients with SLE.

285 ) were significantly higher in patients with SLE.

286 e of morbidity and death among patients with SLE.

287 17A production in T cells from patients with SLE.

288 lpr and NZB/W mice, as well as patients with SLE.

289 can accurately predict APO in patients with SLE.

290 ) were significantly higher in patients with SLE.

291 n susceptible subjects such as patients with SLE.

292 function of T cell subsets in patients with SLE.

293 In people with SLE and in the MRL-Fas(lpr) lupus mouse model, macrophag

294 hough the decrease was greater in women with SLE (difference in trends, P < 0.002).

295 An estimated 93 820 pregnant women with SLE and 78 045 054 without SLE were hospitalized in the

296 oved markedly, particularly among women with SLE.

297 egnant women with SLE and 78 045 054 without SLE were hospitalized in the United States from 1998 thr

298 base and it consisted of 10 patients without SLE for each patient with SLE, based on frequency matchi

299 logist visits compared with patients without SLE.

300 among patients with as well as those without SLE (442 vs. 13 for 1998 to 2000 and <50 vs. 10 for 2013