Abstract:
OBJECTIVE:We sought to determine histologic and gene expression features of clinical improvement in early diffuse cutaneous systemic sclerosis (dcSSc; scleroderma). METHODS:Fifty-eight forearm biopsies were evaluated from 26 individuals with dcSSc in two clinical trials. Histologic/immunophenotypic assessments of global severity, alpha-smooth muscle actin (aSMA), CD34, collagen, inflammatory infiltrate, follicles and thickness were compared with gene expression and clinical data. Support vector machine learning was performed using scleroderma gene expression subset (normal-like, fibroproliferative, inflammatory) as classifiers and histology scores as inputs. Comparison of w-vector mean absolute weights was used to identify histologic features most predictive of gene expression subset. We then tested for differential gene expression according to histologic severity and compared those with clinical improvement (according to the Combined Response Index in Systemic Sclerosis). RESULTS:aSMA was highest and CD34 lowest in samples with highest local Modified Rodnan Skin Score. CD34 and aSMA changed significantly from baseline to 52 weeks in clinical improvers. CD34 and aSMA were the strongest predictors of gene expression subset, with highest CD34 staining in the normal-like subset (p<0.001) and highest aSMA staining in the inflammatory subset (p=0.016). Analysis of gene expression according to CD34 and aSMA binarised scores identified a 47-gene fibroblast polarisation signature that decreases over time only in improvers (vs non-improvers). Pathway analysis of these genes identified gene expression signatures of inflammatory fibroblasts. CONCLUSION:CD34 and aSMA stains describe distinct fibroblast polarisation states, are associated with gene expression subsets and clinical assessments, and may be useful biomarkers of clinical severity and improvement in dcSSc.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Showalter K,Spiera R,Magro C,Agius P,Martyanov V,Franks JM,Sharma R,Geiger H,Wood TA,Zhang Y,Hale CR,Finik J,Whitfield ML,Orange DE,Gordon JKdoi
10.1136/annrheumdis-2020-217840subject
Has Abstractpub_date
2021-02-01 00:00:00pages
228-237issue
2eissn
0003-4967issn
1468-2060pii
annrheumdis-2020-217840journal_volume
80pub_type
杂志文章abstract::Expression of major histocompatibility complex (MHC) class II and other lymphocyte activation markers on peripheral blood and synovial fluid T lymphocytes from patients with rheumatoid arthritis (RA), psoriatic arthritis, and Reiter's syndrome were measured and the mean fluorescence intensities of these antigens were ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.49.2.81
更新日期:1990-02-01 00:00:00
abstract::The fluid and cellular phases of inflammatory resonse have been measured using a technique employing subcutaneous implantation of polyurethane foam cubes impregnated with heat-killed Mycobacterium tuberculosis. Phenylbutazone, azathioprine, aspirin, cyclophosphamide, and prednisolone suppressed fluid response, whereas...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.34.4.326
更新日期:1975-08-01 00:00:00
abstract:BACKGROUND:Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterised by aberrant B cell hyperactivation, whose mechanism is partially understood. METHODS:We performed whole transcriptome sequencing of B cells from three pSS patients and three matched healthy controls (HC). Differentially expressi...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2019-216428
更新日期:2020-04-01 00:00:00
abstract:OBJECTIVES:To develop and validate candidate sets of joints and tendons for assessment of ultrasound (US) joint inflammation in rheumatoid arthritis (RA). METHODS:Patients were included in one of two cohorts from 2010 to June 2013: disease-modifying antirheumatic drug naïve early RA or established RA starting/switchin...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1136/annrheumdis-2015-207572
更新日期:2016-08-01 00:00:00
abstract:OBJECTIVE:To determine how acute but transient inflammation affects the cartilage proteoglycan aggrecan and the value of analyses of synovial fluid to study this. METHODS:For 96 hours after a single intra-articular injection of rabbit knees with human interleukin-1 alpha (IL-1 alpha) or vehicle, articular cartilage an...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.55.8.525
更新日期:1996-08-01 00:00:00
abstract:OBJECTIVE:To examine the influence of intravenous pulsed methylprednisolone (MP) on bone mass. METHODS:38 patients (30 women) with various rheumatic disorders requiring intravenous MP pulse treatment were examined at baseline and after 6 months with dual energy x ray absorptiometry (DXA), measuring hip and lumbar spin...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2003.011734
更新日期:2004-08-01 00:00:00
abstract:BACKGROUND:Physical function in rheumatoid arthritis (RA) has reversible and irreversible components, and is typically assessed by the Health Assessment Questionnaire Disability Index (HAQ). Since irreversible components are expected to increase with longer duration of RA and reduce the ability for improvement in physi...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,meta分析,评审
doi:10.1136/ard.2007.071415
更新日期:2008-02-01 00:00:00
abstract:OBJECTIVES:To characterise optimal screening strategies for latent tuberculosis infection (LTBI) prior to the initiation of anti-tumour necrosis factor therapy. METHODS:Patients in 62 German rheumatology centres were evaluated for LTBI. Each patient was screened with a tuberculin skin test (TST) and one form of an int...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1136/annrheumdis-2011-200941
更新日期:2012-11-01 00:00:00
abstract:OBJECTIVE:To study the association between the occurrence of peripheral arthritis and of acute anterior uveitis during the course of ankylosing spondylitis (AS). METHODS:Retrospective clinical follow up by both chart review and direct patient interview was performed on 271 individuals comprised of 222 local white and ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.54.2.128
更新日期:1995-02-01 00:00:00
abstract:OBJECTIVE:To score systemic activity at diagnosis and correlate baseline activity with survival in a large cohort of patients with primary Sjögren syndrome (SS). PATIENTS AND METHODS:We include 1045 consecutive patients who fulfilled the 2002 classification criteria for primary SS. The clinical and immunological chara...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2014-206418
更新日期:2016-02-01 00:00:00
abstract:BACKGROUND:Treatment of juvenile idiopathic arthritis (JIA) has changed dramatically since the introduction of biological agents in 1999. OBJECTIVE:To evaluate trends in prescription patterns of biological agents and the subsequent outcome of JIA. METHODS:The Arthritis and Biologics in Children register (multicentre ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/annrheumdis-2013-204641
更新日期:2015-07-01 00:00:00
abstract::Serum IgG antibodies to native and denatured human type II collagen (Col II) were measured using an enzyme linked immunosorbent assay (ELISA). One hundred and thirty one patients with various forms of arthritis such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PSA). Reiter's Syndrome...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.47.4.313
更新日期:1988-04-01 00:00:00
abstract:BACKGROUND:Analysis of salivary variables has frequently been proposed as a diagnostic tool for Sjögren's syndrome (SS). Because univocal salivary reference values are lacking, it is currently rather difficult to use sialometry and sialochemistry for diagnosing SS unless major changes have occurred in salivary secretio...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.61.2.137
更新日期:2002-02-01 00:00:00
abstract::Symptomatic osteonecrosis occurred in 8 out of 68 patients with systemic lupus erythematosus. Multiple joints were involved in 3 patients, and weight-bearing joints were most frequently affected. Osteonecrosis tended to occur early in the disease, and the patients had all received corticosteroids. Symptoms tended to o...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.38.5.413
更新日期:1979-10-01 00:00:00
abstract:BACKGROUND:Several studies have reported an association between the presence of the shared epitope (SE) and susceptibility to rheumatoid arthritis (RA). Recent studies have shown that certain HLA-DRB1 alleles in combination with predisposing DQB1 and DQA1 alleles may protect against the development of RA. This model is...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.61.4.351
更新日期:2002-04-01 00:00:00
abstract::The biochemical evidence against incorporation of the purine analogues, allopurinol and oxipurinol, into nucleic acids is reviewed. Cytological experiments have been carried out to investigate the possibility that chromosomal damage might result from exposure of human lymphocytes to these drugs. Lymphocytes from 19 pa...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.35.2.143
更新日期:1976-04-01 00:00:00
abstract:OBJECTIVES:In a post-hoc analysis, we aimed to validate the Lupus Low Disease Activity State (LLDAS) definition as an endpoint in an systemic lupus erythematosus (SLE) Phase IIb randomised controlled trial (RCT) (MUSE [NCT01438489]) and then utilize LLDAS to discriminate between anifrolumab and placebo. METHODS:Patien...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,随机对照试验
doi:10.1136/annrheumdis-2017-212504
更新日期:2018-05-01 00:00:00
abstract:OBJECTIVES:To develop recommendations for monitoring patients with systemic lupus erythematosus (SLE) in clinical practice and observational studies and to develop a standardised core set of variables to monitor SLE. METHODS:We followed the European League Against Rheumatism (EULAR) standardised procedures for guideli...
journal_title:Annals of the rheumatic diseases
pub_type: 共识发展会议,杂志文章,实务指引
doi:10.1136/ard.2009.117200
更新日期:2010-07-01 00:00:00
abstract:BACKGROUND:Preliminary clinical criteria based on age, inflammation, and immobility have been proposed to identify which patients with rheumatoid arthritis (RA) should be examined by dual energy x ray absorptiometry (DXA) to diagnose osteoporosis. The three item criteria have not been evaluated in male patients with RA...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.61.12.1085
更新日期:2002-12-01 00:00:00
abstract::A previous report that C3 activation products are demonstrable in the plasma of subjects with rheumatoid arthritis was reinvestigated using 2-dimensional immunoelectrophoresis. Initially it seemed that results were in agreement, but the occurrence of similar patterns in normal sera and poor reproducibility of results ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.37.1.18
更新日期:1978-02-01 00:00:00
abstract:OBJECTIVE:To investigate the activation of NF-kappaB in the carrageenan rat air pouch model of inflammation in a time course experiment, and the effect of dexamethasone on NF-kappaB activation. METHODS:Air pouch tissue treated with carrageenan (inflamed tissue) was obtained from rats killed at days 1, 2, 3, 6, 14, 21,...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.59.4.303
更新日期:2000-04-01 00:00:00
abstract:OBJECTIVES:To study the ability of technetium-99m hexamethyl propylene amineoxime (HMPAO) labelled lymphocyte scintigraphy to quantify synovial inflammation, and to analyse the kinetics of lymphocyte retention in the joints of patients with rheumatoid arthritis (RA). METHODS:After isolation of the lymphocytes, the cel...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.54.1.39
更新日期:1995-01-01 00:00:00
abstract::The anti-inflammatory effect of single doses and combinations of aspirin and commonly used nonsteroidal anti-inflammatory drugs was investigated by the polyurethane sponge implantation model of acute inflammation. Dose response curves were performed to delineate a suppressive (high) and nonsuppressive (low) dose of ea...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.42.4.439
更新日期:1983-08-01 00:00:00
abstract:OBJECTIVES:People with spondyloarthritis (SpA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) have identified the importance of understanding how their disease and its treatment impacts on their social roles. This requires a reliable and valid standardised measure, and this study evaluates these measurement...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2010.149211
更新日期:2011-10-01 00:00:00
abstract:OBJECTIVES:Human leucocyte antigen shared epitope (SE) alleles are associated with joint destruction, the presence of anticitrullinated protein antibodies (ACPA) and the ACPA fine specificity repertoire in rheumatoid arthritis (RA). A large variation in joint destruction is seen within the ACPA-positive patient populat...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2010.146506
更新日期:2011-08-01 00:00:00
abstract:OBJECTIVES:This integrated analysis presents the safety profile of upadacitinib, a Janus kinase inhibitor, at 15 mg and 30 mg once daily in patients with moderately to severely active rheumatoid arthritis (RA). METHODS:Treatment-emergent adverse events (TEAEs) and laboratory data from five randomised, placebo- or acti...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2020-218510
更新日期:2020-10-28 00:00:00
abstract:OBJECTIVE:To determine whether the heterogeneous clinical response to tumour necrosis factor (TNF)alpha blocking therapy in rheumatoid arthritis (RA) can be predicted by TNFalpha expression in the synovium before initiation of treatment. METHODS:Prior to initiation of infliximab treatment, arthroscopic synovial tissue...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.080440
更新日期:2008-08-01 00:00:00
abstract:BACKGROUND:Antenatal and postnatal treatment with dexamethasone (DEX) may negatively affect the neuropsychological development in children. Maternal anti-Ro/Sjögren's syndrome A (SSA) antibodies may also be associated with learning disabilities in offspring. OBJECTIVE:To assess neuropsychological development in babies...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2005.049866
更新日期:2006-11-01 00:00:00
abstract::Septic arthritis is associated with a definite morbidity which may be related to a delay in diagnosis and hence treatment. The cases of three patients with rheumatoid arthritis and chronic chest disease where the joint sepsis was not the predominant feature are presented. The responsible organism was Streptococcus pne...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.46.6.482
更新日期:1987-06-01 00:00:00
abstract:BACKGROUND:High rheumatoid arthritis (RA) disease activity during pregnancy is associated with a lower birth weight. Active RA is characterised by high circulating levels of cytokines, which can mediate placental growth and remodelling. OBJECTIVES:To assess the influence of maternal serum cytokine levels on birth weig...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/annrheumdis-2012-202539
更新日期:2013-12-01 00:00:00