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High-resolution computed tomography (HRCT) of the chest is the gold standard to diagnose interstitial lung disease (ILD). A prior survey reported that fewer than 60% of SSc-treating rheumatologists order an HRCT for ILD screening in newly diagnosed SSc patients. Since then, efforts were initiated to increase awareness of HRCT as a screening tool. Aim of the present study was to assess efficacy of these awareness programs.European Scleroderma Trials and Research (EUSTAR) and Scleroderma Clinical Trials Consortium (SCTC) members answered a survey about the use of HRCT at diagnosis, the re-screening of patients with a negative baseline HRCT, and the follow-up of HRCT positive SSc-ILD patients. When HRCT was not routinely requested, additional details were collected.Among 205 physician responders, 95.6% would perform an HRCT at SSc diagnosis: 64.9% as routine screening for ILD (65.4% of SSc referral and 63.6% of non-referral physicians) and 30.7% upon clinical suspicion (95.2% in case of crackles on auscultation). Among non-screening physicians, clinical and ethical concerns were major driving factors for not ordering HRCTs. During follow-up, 79.0% of responders would repeat HRCTs in baseline negative cases: 14.1% as routine screening and 64.9% for diagnostic purposes. Finally, 93.2% of responders would repeat a chest HRCT after SSc-ILD diagnosis: 36.6% as yearly routine and 56.6% according to clinical evaluation.The use of baseline HRCT for the screening of SSc-ILD has slightly increased, but awareness programs should be adapted for further improvement. HRCT use in re-screening and follow-up may benefit from validated algorithms.

Objective The greatest genetic effect reported for systemic sclerosis (SSc) lies in the major histocompatibility complex (MHC) locus. Leveraging the largest SSc genome-wide association study, we aimed to fine-map this region to identify novel human leucocyte antigen (HLA) genetic variants associated with SSc susceptibility and its main clinical and serological subtypes. Methods 9095 patients with SSc and 17 584 controls genome-wide genotyped were used to impute and test single-nucleotide polymorphisms (SNPs) across the MHC, classical HLA alleles and their composite amino acid residues. Additionally, patients were stratified according to their clinical and serological status, namely, limited cutaneous systemic sclerosis (lcSSc), diffuse cutaneous systemic sclerosis (dcSSc), anticentromere (ACA), antitopoisomerase (ATA) and anti-RNApolIII autoantibodies (ARA). Results Sequential conditional analyses showed nine SNPs, nine classical alleles and seven amino acids that modelled the observed associations with SSc. This confirmed previously reported associations with HLA-DRB1*11:04 and HLA-DPB1*13:01, and revealed a novel association of HLA-B*08:01. Stratified analyses showed specific associations of HLA-DQA1*02:01 with lcSSc, and an exclusive association of HLA-DQA1*05:01 with dcSSc. Similarly, private associations were detected in HLA-DRB1*08:01 and confirmed the previously reported association of HLA-DRB1*07:01 with ACA-positive patients, as opposed to the HLA-DPA1*02:01 and HLA-DQB1*03:01 alleles associated with ATA presentation. Conclusions This study confirms the contribution of HLA class II and reveals a novel association of HLA class I with SSc, suggesting novel pathways of disease pathogenesis. Furthermore, we describe specific HLA associations with SSc clinical and serological subtypes that could serve as biomarkers of disease severity and progression., This work was supported by the Spanish Ministry of Science and Innovation (grant ref. SAF2015-66761-P and RTI20181013 (32-B-100)), Red de Investigación en Inflamación y Enfermedades Reumáticas from Instituto de Salud Carlos III (RD16/0012/0013) and grants from National Institutes of Health (R01AR073284) and DoD (W81XWH-16-1-0296). MAH was funded by the Spanish Ministry of Science and Innovation through the Juan de la Cierva Incorporacion program (ref. IJC2018-035131-I). GO, AB and ALH were supported by the NIHR Manchester Biomedical Research Centre and Versus Arthritis (grant ref 21754)

ObjectivesTo characterise the safety and tolerability of nintedanib and the dose adjustments used to manage adverse events in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).MethodsIn the SENSCIS trial, patients with SSc-ILD were randomised to receive nintedanib 150 mg two times per day or placebo. To manage adverse events, treatment could be interrupted or the dose reduced to 100 mg two times per day. We assessed adverse events and dose adjustments over 52 weeks.ResultsA total of 576 patients received nintedanib (n=288) or placebo (n=288). The most common adverse event was diarrhoea, reported in 75.7% of patients in the nintedanib group and 31.6% in the placebo group; diarrhoea led to permanent treatment discontinuation in 6.9% and 0.3% of patients in the nintedanib and placebo groups, respectively. In the nintedanib and placebo groups, respectively, 48.3% and 12.2% of patients had ≥1 dose reduction and/or treatment interruption, and adverse events led to permanent discontinuation of the trial drug in 16.0% and 8.7% of patients. The adverse events associated with nintedanib were similar across subgroups defined by age, sex, race and weight. The rate of decline in forced vital capacity in patients treated with nintedanib was similar irrespective of dose adjustments.ConclusionsThe adverse event profile of nintedanib in patients with SSc-ILD is consistent with its established safety and tolerability profile in patients with idiopathic pulmonary fibrosis. Dose adjustment is important to minimise the impact of adverse events and help patients remain on therapy.

ObjectivesGenomic Risk Scores (GRS) successfully demonstrated the ability of genetics to identify those individuals at high risk for complex traits including immune-mediated inflammatory diseases (IMIDs). We aimed to test the performance of GRS in the prediction of risk for systemic sclerosis (SSc) for the first time.MethodsAllelic effects were obtained from the largest SSc Genome-Wide Association Study (GWAS) to date (9 095 SSc and 17 584 healthy controls with European ancestry). The best-fitting GRS was identified under the additive model in an independent cohort that comprised 400 patients with SSc and 571 controls. Additionally, GRS for clinical subtypes (limited cutaneous SSc and diffuse cutaneous SSc) and serological subtypes (anti-topoisomerase positive (ATA+) and anti-centromere positive (ACA+)) were generated. We combined the estimated GRS with demographic and immunological parameters in a multivariate generalised linear model.ResultsThe best-fitting SSc GRS included 33 single nucleotide polymorphisms (SNPs) and discriminated between patients with SSc and controls (area under the receiver operating characteristic (ROC) curve (AUC)=0.673). Moreover, the GRS differentiated between SSc and other IMIDs, such as rheumatoid arthritis and Sjögren’s syndrome. Finally, the combination of GRS with age and immune cell counts significantly increased the performance of the model (AUC=0.787). While the SSc GRS was not able to discriminate between ATA+ and ACA+ patients (AUCConclusionsGRS was successfully implemented in SSc. The model discriminated between patients with SSc and controls or other IMIDs, confirming the potential of GRS to support early and differential diagnosis for SSc.

We thank Sofia Vargas and Gema Robledo for her excellent technical assistance and all the patients and control donors for their essential collaboration. We thank WTCCC (Welcome Trust Case Control Consortium) for the access to GWAS data of Crohn’s disease patients and healthy controls, Banco Nacional de ADN (University of Salamanca, Spain) who supplied part of the control DNA samples, and dbGap for granting access to the IBD Genetics Consortium (IBDGC) Crohn’s Disease GWAS data (phs000130.v1.p1). The IBDGC Crohn’s Disease Genome-Wide Association Study was conducted by the IBDGC Investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). This manuscript was not prepared in collaboration with Investigators of the IBDGC Crohn’s Disease Genome-Wide Association Study and does not necessarily reflect the opinions or views of the IBDGC Crohn’s Disease Genome-Wide Association Study, the NIDDK Central Repositories, or the NIDDK., Genome-wide association studies (GWASs) have identified a number of genetic risk loci associated with systemic sclerosis (SSc) and Crohn’s disease (CD), some of which confer susceptibility to both diseases. In order to identify new risk loci shared between these two immune-mediated disorders, we performed a cross-disease meta-analysis including GWAS data from 5,734 SSc patients, 4,588 CD patients and 14,568 controls of European origin. We identified 4 new loci shared between SSc and CD, IL12RB2, IRF1/SLC22A5, STAT3 and an intergenic locus at 6p21.31. Pleiotropic variants within these loci showed opposite allelic effects in the two analysed diseases and all of them showed a significant effect on gene expression. In addition, an enrichment in the IL-12 family and type I interferon signaling pathways was observed among the set of SSc-CD common genetic risk loci. In conclusion, through the first cross-disease meta-analysis of SSc and CD, we identified genetic variants with pleiotropic effects on two clinically distinct immune-mediated disorders. The fact that all these pleiotropic SNPs have opposite allelic effects in SSc and CD reveals the complexity of the molecular mechanisms by which polymorphisms affect diseases., This work was supported by the Spanish Ministry of Economy and Competitiveness (SAF2015-66761-P; IPT-010000-2010-36, cofunded by the European Regional Development Fund), Consejería de Innovación, Ciencia y Tecnología, Junta de Andalucía (Spain) (P12-BIO-1395) and the Cooperative Research Thematic Network (RETICS) programme (RD16/0012/0013) (RIER) from Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Economy, Industry and Competitiveness). AM is recipient of a Miguel Servet fellowship (CP17/00008) from ISCIII (Spanish Ministry of Economy, Industry and Competitiveness). DGS was supported by the Spanish Ministry of Economy and Competitiveness through the FPI programme (SAF2015-66761-P). This work is part of the Doctoral Thesis “Bases Genéticas de la Esclerosis Sistémica: Integrando Genómica y Transcriptómica”.

Antisense long non-coding RNAs (AS lncRNAs) have increasingly been recognized as important regulators of gene expression and they have been found to play key roles in several diseases. However, very little is known about the role of AS lncRNAs in fibrotic diseases such as systemic sclerosis (SSc). Our recent screening experiments by RNA sequencing showed that ovarian tumor domain containing 6B antisense RNA1 (OTUD6B-AS1) and its sense gene OTUD6B were significantly downregulated in SSc skin biopsies. Therefore, we aimed to identify key regulators of OTUD6B-AS1 and to analyze the functional relevance of OTUD6B-AS1 in SSc. OTUD6B-AS1 and OTUD6B expression in SSc and healthy control (HC) dermal fibroblasts (Fb) after stimulation with transforming growth factor-β (TGFβ), Interleukin (IL)-4, IL-13, and platelet-derived growth factor (PDGF) was analyzed by qPCR. To identify the functional role of OTUD6B-AS1, dermal Fb or human pulmonary artery smooth muscle cells (HPASMC) were transfected with a locked nucleic acid antisense oligonucleotide (ASO) targeting OTUD6B-AS1. Proliferation was measured by BrdU and real-time proliferation assay. Apoptosis was measured by Caspase 3/7 assay and Western blot for cleaved caspase 3. While no difference was recorded at the basal level between HC and SSc dermal Fb, the expression of OTUD6B-AS1 and OTUD6B was significantly downregulated in both SSc and HC dermal Fb after PDGF stimulation in a time-dependent manner. Only mild and inconsistent effects were observed with TGFβ, IL-4, and IL-13. OTUD6B-AS1 knockdown in Fb and HPASMC did not affect extracellular matrix or pro-fibrotic/proinflammatory cytokine production. However, OTUD6B-AS1 knockdown significantly increased Cyclin D1 expression at the mRNA and protein level. Moreover, silencing of OTUD6B-AS1 significantly reduced proliferation and suppressed apoptosis in both dermal Fb and HPASMC. OTUD6B-AS1 knockdown did not affect OTUD6B expression at the mRNA level and protein level. Our data suggest that OTUD6B-AS1 regulates proliferation and apoptosis via cyclin D1 expression in a sense gene independent manner. This is the first report investigating the function of OTUD6B-AS1. Our data shed light on a novel apoptosis resistance mechanism in Fb and vascular smooth muscle cells that might be relevant for pathogenesis of SSc.

To identify baseline features that predict progression of hand contractures and to assess the effect of contractures on functional status in the prospective GENISOS cohort.Rate of decline in hand extension, as an indicator of hand contracture, was the primary outcome. We assessed longitudinal hand extension measurements, modified Health Assessment Questionnaire (MHAQ) score, Medical Outcomes Study Short Form-36 (SF-36) physical function score, and demographic, clinical, and serological variables. Subjects with ≥ 2 hand measurements at least 6 months apart were included.A total of 1087 hand measurements for 219 patients were available over an average of 8.1 ± 4.8 years. Hand extension decreased on average by 0.11 cm/year. Antitopoisomerase I antibody (ATA) positivity and higher modified Rodnan Skin Score (mRSS) were predictive of faster decline in hand extension (p = 0.009 and p = 0.046, respectively). In a subgroup analysis of 62 patients with ≤ 2 years from SSc onset, ATA and diffuse disease type were associated with faster decline in hand extension; anticentromere positivity was associated with slower rate of decline. Although the rate of decline in patients with disease duration ≤ 2 years was numerically higher, the difference was not statistically significant. Hand extension continued to decline in a linear fashion over time and was inversely related to overall functional status.ATA was predictive of contracture development in both early disease (≤ 2 yrs) and in the overall cohort. Hand extension declined linearly over time and was inversely associated with MHAQ and SF-36 scores. ATA positivity and higher baseline mRSS were predictive of faster decline in hand extension.

Contains fulltext : 194824.pdf (Publisher’s version ) (Closed access) Objectives: The Scleroderma Patient-centered Intervention Network (SPIN) Cohort is a web-based cohort designed to collect patient-reported outcomes at regular intervals as a framework for conducting trials of psychosocial, educational, self-management and rehabilitation interventions for patients with SSc. The aim of this study was to present baseline demographic, medical and patient-reported outcome data of the SPIN Cohort and to compare it with other large SSc cohorts. Methods: Descriptive statistics were used to summarize SPIN Cohort characteristics; these were compared with published data of the European Scleroderma Trials and Research (EUSTAR) and Canadian Scleroderma Research Group (CSRG) cohorts. Results: Demographic, organ involvement and antibody profile data for SPIN (N = 1125) were generally comparable with that of the EUSTAR (N = 7319) and CSRG (N = 1390) cohorts. There was a high proportion of women and White patients in all cohorts, though relative proportions differed. Scl70 antibody frequency was highest in EUSTAR, somewhat lower in SPIN, and lowest in CSRG, consistent with the higher proportion of interstitial lung disease among dcSSc patients in SPIN compared with in CSRG (48.5 vs 40.3%). RNA polymerase III antibody frequency was highest in SPIN and remarkably lower in EUSTAR (21.1 vs 2.4%), in line with the higher prevalence of SSc renal crisis (4.5 vs 2.1%) in SPIN. Conclusion: Although there are some differences, the SPIN Cohort is broadly comparable with other large prevalent SSc cohorts, increasing confidence that insights gained from the SPIN Cohort should be generalizable, although it should be noted that all three cohorts include primarily White participants. 9 p.

Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc-RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc-RA loci through an interdisease meta-genome-wide association (meta-GWAS) strategy.The study was designed as a meta-analysis combining GWAS data sets of patients with SSc and patients with RA, using a strategy that allowed identification of loci with both same-direction and opposite-direction allelic effects. The top single-nucleotide polymorphisms were followed up in independent SSc and RA case-control cohorts. This allowed an increase in the sample size to a total of 8,830 patients with SSc, 16,870 patients with RA, and 43,393 healthy controls.This cross-disease meta-analysis of the GWAS data sets identified several loci with nominal association signals (P 5 × 10(-6) ) that also showed evidence of association in the disease-specific GWAS scans. These loci included several genomic regions not previously reported as shared loci, as well as several risk factors that were previously found to be associated with both diseases. Follow-up analyses of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these 2 diseases (Pcombined = 3.29 × 10(-12) ). Analysis of the biologic relevance of the known SSc-RA shared loci identified the type I interferon and interleukin-12 signaling pathways as the main common etiologic factors.This study identified a novel shared locus, IRF4, for the risk of SSc and RA, and highlighted the usefulness of a cross-disease GWAS meta-analysis strategy in the identification of common risk loci.

OBJECTIVES: TYK2 is a common genetic risk factor for several autoimmune diseases. This gene encodes a protein kinase involved in interleukin 12 (IL-12) pathway, which is a well-known player in the pathogenesis of systemic sclerosis (SSc). Therefore, we aimed to assess the possible role of this locus in SSc. METHODS: This study comprised a total of 7103 patients with SSc and 12 220 healthy controls of European ancestry from Spain, USA, Germany, the Netherlands, Italy and the UK. Four TYK2 single-nucleotide polymorphisms (V362F (rs2304256), P1104A (rs34536443), I684S (rs12720356) and A928V (rs35018800)) were selected for follow-up based on the results of an Immunochip screening phase of the locus. Association and dependence analyses were performed by the means of logistic regression and conditional logistic regression. Meta-analyses were performed using the inverse variance method. RESULTS: Genome-wide significance level was reached for TYK2 V362F common variant in our pooled analysis ( p=3.08×10(−13), OR=0.83), while the association of P1104A, A928V and I684S rare and low-frequency missense variants remained significant with nominal signals ( p=2.28×10(−3), OR=0.80; p=1.27×10(−3), OR=0.59; p=2.63×10(−5), OR=0.83, respectively). Interestingly, dependence and allelic combination analyses showed that the strong association observed for V362F with SSc, corresponded to a synthetic association dependent on the effect of the three previously mentioned TYK2 missense variants. CONCLUSIONS: We report for the first time the association of TYK2 with SSc and reinforce the relevance of the IL-12 pathway in SSc pathophysiology.

Despite being a common problem in systemic sclerosis (SSc; scleroderma), the extant literature on pain has primarily focused on biomedical correlates, or bivariate relationships with a few psychological characteristics. There is a need to investigate the more heuristic biopsychosocial model, which incorporates the simultaneous contributions of medical, psychological, and social variables in understanding pain.Patients with SSc (n = 333) received clinical examinations and completed self-report surveys at enrollment in the Genetics versus Environment in Scleroderma Outcome Study. Latent profile analysis was used to derive biopsychosocial profiles of patients using skin thickening, percent predicted forced vital lung capacity, perceived physical health, health worry, mental health, and social support. The profiles were examined in relation to pain and pain medication usage.A 3-profile solution provided the best fit to the data. Based on the biopsychosocial indicators, the profiles were characterized as managing (n = 217), resilient (n = 86), and distressed (n = 30). Between-group differences for pain emerged, with the distressed group, whose disease was less severe than the resilient group, reporting the highest pain and the greatest utilization of pain medication.Clinicians should consider biopsychosocial characteristics as contributing factors to the experience of pain in patients with SSc. Patients who are similar to those in the distressed profile may be at an increased risk for pain and would likely benefit from a referral to a behavioral health or other ancillary service provider for pain management, rather than relying solely on pharmacologic therapies.

[Introduction] A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy., [Methods] Sixty-six non-HLA SNPs showing a P value, [Results] We observed nominal associations for both PPARG rs310746 (P MH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (P MH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (P MH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis., [Conclusion] Our results suggest a role of PPARG gene in the development of SSc., This work was supported by the following grants: JM was funded by GEN-FER from the Spanish Society of Rheumatology, SAF2009-11110 and SAF2012-34435 from the Spanish Ministry of Economy and Competitiveness, CTS-4977, and CTS-180 from Junta de Andalucía, and is sponsored by the Orphan Disease Program grant from the European League Against Rheumatism (EULAR). This study was also funded by PI-0590-2010, from Consejería de Salud y Bienestar Social, Junta de Andalucía, Spain. JLCR and JM are funded by Consejería de Salud, Junta de Andalucía, through PI-0590-2010. ELI was supported by Ministerio de Educación, Cultura y Deporte through the program FPU. TRDJR was funded by the VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation (National Reumafonds). TW was granted by DFG WI 1031/6.1. Study on USA samples were supported by US National Institutes of Health and National Institute of Arthritis and Musculoskeletal Diseases (NIH-NIAMS) R01-AR-055258, Two-Stage Genome Wide Association Study in Systemic Sclerosis (MDM) and by the NIH-NIAMS Center of Research Translation (CORT) in SSc (P50AR054144) (MDM, FCA, FKT), the NIH-NIAMS SSc Family Registry and DNA Repository (N01-AR-0-2251) (MDM), NIH-KL2RR024149 (SA), K23AR061436 (SA), and the Department of Defense Congressionally Directed Medical Research Programs (W81XWH-07-01-0111) (MDM).

We undertook this hypothesis-generating study to identify skin transcripts correlating with severity of interstitial lung disease (ILD) in systemic sclerosis (SSc).Skin biopsy samples from 59 patients enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort or an open-label imatinib study (baseline visit) were examined by global gene expression analysis using Illumina HT-12 arrays. Skin transcripts correlating with concomitantly obtained forced vital capacity (FVC) values and the modified Rodnan skin thickness score (MRSS) were identified by quantitative trait analysis. Also, immunofluorescence staining for selected transcripts was performed in affected skin and lung tissue. Plasma levels of CCL2, soluble SELP, and soluble P-selectin glycoprotein ligand 1 (sPSGL-1) were examined in all patients enrolled in the GENISOS cohort (n = 266).Eighty-two skin transcripts correlated significantly with FVC. This gene list distinguished patients with more severe ILD (FVC70% predicted) in unsupervised hierarchical clustering analysis (P0.001). These genes included SELP, CCL2, and matrix metalloproteinase 3, which are involved in extravasation and adhesion of inflammatory cells. Among the FVC correlates, 8 genes (CCL2, HAPLN3, GPR4, ADCYAP1, WARS, CDC25B, PLP1, and STXBP6) also correlated with the MRSS. Immunofluorescence staining revealed that SELP and CCL2 were also overexpressed in affected skin and lung tissue from SSc patients compared to those from controls. Plasma levels of CCL2 and sPSGL-1 correlated with concomitantly obtained FVC values (r = -0.22, P = 0.001 and r = 0.17, P = 0.015, respectively). This relationship was independent of potential confounders (age, sex, ethnicity, smoking status, anti-topoisomerase I positivity, treatment with immunosuppressive agents, MRSS, disease type, and disease duration).A limited number of skin transcripts including genes involved in extravasation and adhesion of inflammatory cells correlate with severity of ILD.

There are no identified clinical markers that reliably predict long-term progression of interstitial lung disease (ILD) in systemic sclerosis (SSc; scleroderma). Elevated C-reactive protein (CRP) levels have been reported in SSc patients. We examined the predictive significance of CRP level for long-term ILD progression in a large early SSc cohort.First, the CRP levels were compared between baseline samples of 266 SSc patients enrolled in the Genetics Versus Environment in Scleroderma Outcome Study cohort and 97 unaffected matched controls. Subsequently, the correlation between CRP levels and concomitantly obtained markers of disease severity was assessed. Serially obtained % predicted forced vital capacity (FVC) was used to examine the long-term ILD progression. The predictive significance of CRP level was investigated by a joint analysis of longitudinal measurements (serial FVCs up to 13 years) and survival data. This approach allowed inclusion of all 1,016 FVC measurements and accounted for survival dependency.We confirmed that baseline CRP levels were higher in SSc patients than controls. CRP levels were associated with absence of anticentromere antibodies and correlated with the concomitant severity of lung, skin, and joint involvement. More importantly, higher baseline CRP levels were associated with shorter survival (P0.001) and predicted the long-term decline in FVC independent of potential confounders (age at baseline, sex, ethnicity, disease type, current smoking, body mass index, topoisomerase status, and treatment with immunosuppressive agents) in the multivariable model (P = 0.006).Baseline CRP levels are predictive of long-term ILD progression. CRP level might aid clinicians in identifying patients that require more intensive monitoring and treatment.

Introduction: Traditionally, assessment in axial Spondyloarthritis (aSpA) includes the evaluation of the capacity to execute tasks, conceptualized as physical function. The role of physical activity, defined as movement-related energy expenditure, is largely unknown and almost exclusively studied using patient-reported outcome measures. The aims of this observational cross-sectional study are to compare physical activity between patients with aSpA and healthy controls (HC) and to evaluate the contribution of disease activity to physical activity differences between groups. Methods: Forty patients with aSpA were matched by age, gender, period of data acquisition in terms of days and season to 40 HC. Physical activity was measured during five consecutive days (three weekdays and two weekend days) using ambulatory monitoring (SenseWear Armband). Self-reported disease activity was measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Differences in physical activity between patients with aSpA and HC were examined with Wilcoxon signed-rank tests and a mixed linear model. Difference scores between patients and HC were correlated with disease activity. Results: Average weekly physical activity level (Med(IQR); HC: 1.54(1.41-1.73); aSpA: 1.45(1.31-1.67), MET) and energy expenditure (HC: 36.40(33.43-41.01); aSpA: 34.55(31.08-39.41), MET. hrs/day) were significantly lower in patients with aSpA. Analyses across intensity levels revealed no significant differences between groups for inactivity and time spent at light or moderate physical activities. In contrast, weekly averages of vigorous (HC: 4.02(1.20-12.60); aSpA: 0.00(0.00-1.20), min/d), very vigorous physical activities (HC0.00(0.00-1.08); aSpA: 0.00(0.00-0.00), mind/d) and moderate/(very) vigorous combined (HC2.41(1.62-3.48); aSpA: 1.63(1.20-2.82), hrs/d) were significantly lower in patients with aSpA. Disease activity did not interact with differences in physical activity between patients with aSpA and HC, evidenced by non-significant and very low correlations (range: 20.06-0.17) between BASDAI and HC-aSpA patients’ difference scores. Conclusions: Patients with aSpA exhibit lower physical activity compared to HC and these differences are independent of self-reported disease activity. Further research on PA in patients with aSpA should be prioritized. article-number: e85309 unique-id: ISI:000332396200006 ispartof: Plos One vol:9 issue:2 ispartof: location:United States status: published