scholarly journals POS0318 CLINICAL PHENOTYPE IN SCLERODERMA PATIENTS WITH ANTI-TOPOISOMERASE I POSITIVITY AND LIMITED CUTANEOUS FORM: DATA FROM THE EUSTAR DATABASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 386-387
Author(s):  
E. Zanatta ◽  
D. Huscher ◽  
P. Airò ◽  
A. Balbir-Gurman ◽  
E. Siegert ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Lung Disease ◽  
Mortality Risk ◽  
Research Funding ◽  
Topoisomerase I ◽  
Rna Polymerase Iii ◽  
The Other ◽  
Organ Involvement ◽  
Cutaneous Form ◽  
Over Time

Background:There is renewed interest in the role of autoantibodies to predict outcomes in systemic sclerosis (SSc). Among the newly identified subsets, patients with limited cutaneous form (lcSSc) but anti-topoisomerase I antibodies (Scl70) positivity draw particular attention, and namely, assessing the risk of developing interstitial lung disease (ILD) —the main cause of death in SSc—to improve the management of Scl70-lcSSc patients.Objectives:We aimed to characterize patients with Scl70-lcSSc in the large multicenter European Scleroderma Trial and Research (EUSTAR) cohort.Methods:The EUSTAR database was locked in July 2019. We included all patients fulfilling 1980 ACR and/or 2013 ACR/EULAR criteria for SSc, with disease duration at database entry ≤3 yrs and known and stable skin form during the first 3 yrs. Patients with lcSSc were compared: Scl70-lcSSc (target group) vs. ACA-lcSSc and ANA-lcSSc (Step 1); and Scl70-lcSSc vs. Scl70-dcSSc (Step 2). In the ANA subgroup we included ANA+ patients with negative SSc-specific antibodies (Scl70, ACA, RNA polymerase III). In each step, we performed 5 generalized mixed models (GMM) for the risk of the new onset of ILD (defined by imaging), primary myocardial involvement (PMI), pulmonary hypertension (PH), “any severe” (ILD+PMI+PH+scleroderma renal crisis) and all-cause-mortality. An additional GMM assessed the risk of forced vital capacity (FVC) decline ≥10% vs. FVC value at ILD onset. Each GMM was adjusted for age, sex and confounders.Results:Overall, 1285 SSc patients were included: 1068 (83%) females, 860 (67%) lcSSc and 425 (33%) dcSSc. Among patients with lcSSc, 537 (62%) had ACA+, 194 (23%) Scl70+ and 129 (15%) ANA+; 425 patients had dcSSc and Scl70+. Median follow-up was similar in all 4 groups: 7.2 to 8.1 yrs.Step 1: At baseline, Scl70-lcSSc patients had significantly shorter time from Raynaud’s phenomenon (RP) to SSc onset, higher mRSS (5.8±4.8 vs. 4.3±4, p=0.001), and higher rate of articular and muscular involvement vs. ACA-lcSSc patients (Figure 1). No differences were found between Scl70-lcSSc and ANA-lcSSc comparing the aforementioned variables. ILD was more frequent in Scl70-lcSSc (46%) than in ACA-lcSSc (10%) and ANA-lcSSc (25%), as well as restrictive lung disease. GMM showed that Scl70-lcSSc carries a higher risk of ILD than both ACA-lcSSc (HR 4.55, 95%CI 3.23-6.67) and ANA-lcSSc (HR 2.17, 95%CI 1.39-3.45), with a rate of FVC decline ≥10% over time similar to the other limited forms. In Scl70-lcSSc patients the risk of “any severe” organ involvement was similar to ANA-lcSSc and higher than ACA-lcSSc (HR 1.89, 95%CI 1.40-2.50). In particular, Scl70-lcSSc shows a risk of PMI similar to ANA-lcSSc and lower than ACA-lcSSc; no differences regarding PH risk. The mortality risk in patients with Scl70-lcSSc was similar to the other limited forms’.Step 2: At baseline, time from RP to SSc onset was longer in patients with Scl70-lcSSc, with less frequent joint synovitis and tendon friction rubs vs. patients with Scl70-dcSSc. Conversely, the frequency of muscular, cardiac and pulmonary involvement was similar. The risk of ILD in Scl70-lcSSc patients was similar to Scl70-dcSSc, with a lower risk of FVC decline ≥10% over time. The risk of “any severe” involvement (HR 0.66, 95%CI 0.49-0.83), PMI and PH was lower and the mortality risk tended to be lower (HR 0.57, 95%CI 0.33-1.01, p=0.053) vs. Scl70-dcSSc.Conclusion:In our large multicenter EUSTAR cohort one quarter of lcSSc patients were Scl70+. We show a ranking for major organ involvement within lcSSc: Scl70 the most severe, ANA+ intermediate and ACA the milder form. Scl70-dcSSc patients present the most severe phenotype, and Scl70 positivity, more than the cutaneous subset, is strongly predictive of ILD, whereas other variables may influence progression. These results may provide new insight to improve the management of Scl70-lcSSc patients.Disclosure of Interests:Elisabetta Zanatta: None declared, Dörte Huscher: None declared, Paolo Airò: None declared, Alexandra Balbir-Gurman: None declared, Elise Siegert: None declared, Augusta Ortolan: None declared, Marco Matucci-Cerinic: None declared, Franco Cozzi: None declared, Gabriela Riemekasten: None declared, Anna-Maria Hoffmann-Vold: None declared, Oliver Distler Speakers bureau: has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Consultant of: has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: Kymera Therapeutics, Mitsubishi Tanabe, Armando Gabrielli: None declared, Stefan Heitmann: None declared, Nicolas Hunzelmann: None declared, Carlomaurizio Montecucco: None declared, Jadranka Morovic-Vergles: None declared, Camillo Ribi: None declared, Andrea Doria: None declared, Yannick Allanore: None declared

scholarly journals Gastric Antral Vascular Ectasia and Its Clinical Correlates in Patients with Early Diffuse Systemic Sclerosis in the SCOT Trial

2013 ◽  
Vol 40 (4) ◽  
pp. 455-460 ◽  
Author(s):  
Emily W. Hung ◽  
Maureen D. Mayes ◽  
Roozbeh Sharif ◽  
Shervin Assassi ◽  
Victor I. Machicao ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Topoisomerase I ◽  
Rna Polymerase Iii ◽  
Negative Association ◽  
Upper Gastrointestinal Endoscopy ◽  
Gastric Antral Vascular Ectasia ◽  
Clinical Correlates ◽  
Vascular Ectasia ◽  
Diffuse Systemic Sclerosis ◽  
Vascular Ectasias

Objective.To describe the prevalence and clinical correlates of endoscopic gastric antral vascular ectasia (GAVE; “watermelon stomach”) in early diffuse systemic sclerosis (SSc).Methods.Subjects with early, diffuse SSc and evidence of specific internal organ involvement were considered for the Scleroderma: Cyclophosphamide Or Transplant (SCOT) trial. In the screening procedures, all patients underwent upper gastrointestinal endoscopy. Patients were then categorized into those with or without endoscopic evidence of GAVE. Demographic data, clinical disease characteristics, and autoantibody data were compared using Pearson chi-square or Student t tests.Results.Twenty-three of 103 (22.3%) individuals were found to have GAVE on endoscopy. Although not statistically significant, anti-topoisomerase I (anti-Scl70) was detected less frequently among those with GAVE (18.8% vs 44.7%; p = 0.071). Similarly, anti-RNP antibodies (anti-U1 RNP) showed a trend to a negative association with GAVE (0 vs 18.4%; p = 0.066). There was no association between anti-RNA polymerase III and GAVE. Patients with GAVE had significantly more erythema or vascular ectasias in other parts of the stomach (26.1% vs 5.0%; p = 0.003).Conclusion.Endoscopic GAVE was present on screening in almost one-fourth of these highly selected patients with early and severe diffuse SSc. While anti-Scl70 and anti-U1 RNP trended toward a negative association with GAVE, there was no correlation between anti-RNA Pol III and GAVE. Patients with GAVE had a higher frequency of other gastric vascular ectasias outside the antrum, suggesting that GAVE may represent part of the spectrum of the vasculopathy in SSc.

scholarly journals Association between gene expression profiling of skin lesion and autoantibody in patients with systemic sclerosis

2020 ◽  
Author(s):  
Jun Inamo
Keyword(s):  
Gene Expression ◽  
Systemic Sclerosis ◽  
Skin Lesion ◽  
Topoisomerase I ◽  
Cellular Response ◽  
Rna Polymerase Iii ◽  
Functional Enrichment ◽  
Keratinocyte Differentiation ◽  
Study Cohort ◽  
Specific Autoantibody

AbstractObjectiveThe aim of this study was to investigate relevance between type of autoantibody and gene expression profile in skin lesion of systemic sclerosis (SSc), and identify specifically dysregulated pathways.MethodsSixty-one patients with SSc from the Genetics versus Environment in Scleroderma Outcome Study cohort and thirty-six healthy controls (HC) are included. Differentially expressed genes (DEGs) were extracted and functional enrichment and pathways analysis were conducted.ResultsCompared with HC, lists consisting of 2, 71, 10, 144 and 78 DEGs were created for patients without specific autoantibody, anti-centromere (ACA), anti-U1 RNP (RNP), anti-RNA polymerase III (RNAP) and anti-topoisomerase I (ATA) antibody, respectively. While part of enriched pathways overlapped, distinct pathways were identified except those without specific autoantibody: keratinocyte differentiation in ACA, NF-kB signaling and cellular response to transforming growth factor beta stimulus in RNAP, interferon alpha/beta signaling of RNP and cellular response to stress in ATA.ConclusionPathogenic pathways were identified according to type of autoantibodies by leveraging gene expression data of patients and controls from multi-center cohort. The current study will promote to explore new therapeutic target for SSc.Key messageDistinct pathways are associated with type of autoantibody in skin lesion of systemic sclerosis.

scholarly journals Predictors of progression in systemic sclerosis patients with interstitial lung disease

2020 ◽  
Vol 55 (5) ◽  
pp. 1902026 ◽  
Author(s):  
Oliver Distler ◽  
Shervin Assassi ◽  
Vincent Cottin ◽  
Maurizio Cutolo ◽  
Sonye K. Danoff ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Disease Progression ◽  
Topoisomerase I ◽  
Diagnostic Tools ◽  
Systemic Autoimmune Disease ◽  
High Resolution Computed Tomography ◽  
Time Period ◽  
Organ Systems

Systemic sclerosis (SSc) is a systemic autoimmune disease affecting multiple organ systems, including the lungs. Interstitial lung disease (ILD) is the leading cause of death in SSc.There are no valid biomarkers to predict the occurrence of SSc-ILD, although auto-antibodies against anti-topoisomerase I and several inflammatory markers are candidate biomarkers that need further evaluation. Chest auscultation, presence of shortness of breath and pulmonary function testing are important diagnostic tools, but lack sensitivity to detect early ILD. Baseline screening with high-resolution computed tomography (HRCT) is therefore necessary to confirm an SSc-ILD diagnosis. Once diagnosed with SSc-ILD, patients' clinical courses are variable and difficult to predict, although certain patient characteristics and biomarkers are associated with disease progression. It is important to monitor patients with SSc-ILD for signs of disease progression, although there is no consensus about which diagnostic tools to use or how often monitoring should occur. In this article, we review methods used to define and predict disease progression in SSc-ILD.There is no valid definition of SSc-ILD disease progression, but we suggest that either a decline in forced vital capacity (FVC) from baseline of ≥10%, or a decline in FVC of 5–9% in association with a decline in diffusing capacity of the lung for carbon monoxide of ≥15% represents progression. An increase in the radiographic extent of ILD on HRCT imaging would also signify progression. A time period of 1–2 years is generally used for this definition, but a decline over a longer time period may also reflect clinically relevant disease progression.

scholarly journals AB0589 THE IMPORTANCE OF A SYSTEMIC SCLEROSIS CLINIC IN A TERTIARY REFERRAL CENTER – A PORTUGUESE EXPERIENCE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1591.1-1591
Author(s):  
P. Martins ◽  
E. Dourado ◽  
J. E. Fonseca ◽  
I. Cordeiro ◽  
C. Resende
Keyword(s):  
Pulmonary Hypertension ◽  
Systemic Sclerosis ◽  
Pulmonary Fibrosis ◽  
Topoisomerase I ◽  
Rna Polymerase Iii ◽  
Gastric Disease ◽  
Digital Ulcers ◽  
Medical Specialties ◽  
Patient Pathways ◽  
Kidney Involvement

Background:Systemic sclerosis (SSc) is a rare systemic rheumatic disease (SRD) characterized by small vessel inflammation and fibrosis of skin and internal organs. Pulmonary and cardiac involvement contribute to both morbidity and mortality associated with the disease. A multidisciplinary approach with strict monitoring is therefore key to attain clinical success.Objectives:To describe the organization and patient pathways of our SSc outpatient clinic.Methods:Observational study using data extracted from Reuma.pt/SSc (a subset of the Rheumatic Diseases Portuguese Register). Data extracted included demographic variables and clinical and immunological manifestations. The disease was classified according to the 2013 ACR/EULAR criteria. Our SSc clinic is managed by two dedicated Rheumatologists and up to two Rheumatology residents on a weekly basis, but it is a dynamic multidisciplinary clinic where various medical specialties collaborate closely. There are two associated subspecialty clinics (pulmonary hypertension and pulmonary fibrosis) where the Rheumatologists engage with pneumologists and cardiologists, allowing greater collaboration in the management of these patients. Patients’ data is systematically registered in Reuma.pt/SSc as a part of the routine activity of this clinic, contributing to real-world data on SSc.Results:A total of 220 patients were registered between July 2011 and June 2019. 196 (89.1%) were female, with a mean age of 58.9±14 years and a mean disease duration of 14.6±9 years. Ninety-seven patients (44.1%) had limited cutaneous SSc, 52 (23.6%) had diffuse cutaneous SSc, 35 (15.9%) had overlap SSc, 24 (10.9%) had preclinical SSc and 12 (5.4%) had SSc sine scleroderma. Raynaud phenomenon was present in 92% of the SSc patients and 40% had a history of digital ulcers. Gastrointestinal manifestations included esophageal dismotility in 39.5% of patients, gastric disease in 24.4% and intestinal involvement in 15.5%. Pulmonary involvement was found in 47.6% of SSc patients, heart disease in 43.6% and kidney involvement in only two patients. Antinuclear antibodies were positive in 92.2% of the patients, anti-centromere in 44.1%, anti-topoisomerase I antibodies in 39.1%, anti-U1RNP in 4.5% and only three patients had anti-PM-Scl and one had anti-RNA polymerase III. 31 patients were lost to follow-up and 32 died. 18 patients are currently being followed up in the pulmonary hypertension clinic and seven in the pulmonary fibrosis clinic.Conclusion:The implementation of a standardized approach with regular multidisciplinary work has proven very helpful in evaluating patients with SSc. The continuous registry of patients in Reuma.pt/SSc has been essential for patient care, research and healthcare planning.Disclosure of Interests:None declared

scholarly journals SAT0326 SYSTEMIC SCLEROSIS WITHOUT ANTINUCLEAR ANTIBODIES: A MULTI-CENTER STUDY OF EUSTAR COHORT IN CHINA

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1108.1-1109
Author(s):  
M. Hui ◽  
J. Zhou ◽  
L. Zhang ◽  
X. Duan ◽  
M. Li ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Clinical Features ◽  
Topoisomerase I ◽  
Antinuclear Antibody ◽  
Antinuclear Antibodies ◽  
Rna Polymerase Iii ◽  
Laboratory Data ◽  
Positive Group ◽  
Significant Difference ◽  
Chi Square Analysis

Background:The presence of circulating antinuclear antibodies (ANAs) is a hallmark of immune dysregulation and malfunction in patients with systemic sclerosis (SSc)[1]. A variety of ANAs[2], including anti-centromere antibody, anti-topoisomerase I antibody, and anti-RNA polymerase III antibody, are associated with unique sets of disease manifestations and widely used in routine clinical practice for diagnosis, clinical subgrouping, risk stratification and prediction of future organ involvements and prognosis in SSc patients[3,4].Objectives:This study aimed to investigate the clinical features of SSc patients with negative ANAs in a European League Against Rheumatism Scleroderma Trials and Research Group (EUSTAR) and Chinese Rheumatism Data Center (CRDC) multi-center cohort in China.Methods:Patients were prospectively recruited between April 2008 and June 2019 based on the EUSTAR database and CRDC multi-center cohort from 154 clinical centers nationwide, all of whom fulfilled the 2013 ACR/EULAR classification criteria for systemic sclerosis. Antinuclear antibody testing result was intensively collected. Demographic, clinical, and laboratory data were compared between ANA-positive SSc patients and those with negative ANAs. T-test and chi-square analysis were performed in the comparisons.Results:Antinuclear antibodies were detected in 2129 out of 2809 systemic sclerosis patients enrolled in the multi-center cohort and 4.2% of them were negative. There was significant difference between patients with negative and positive ANAs based on gender (29/60 vs 294/1746, p<0.001). The presence of Raynaud’s phenomenon is less common (71.8% vs 99.8%, p<0.001) in the ANA-negative patients. In addition, compared with ANA-positive patients, the incidence of certain critical organ involvements, including gastroesophageal reflux (5.6% vs 18.5%, p=0.002), interstitial lung disease (65.2% vs 77.9%, p=0.015) and pulmonary arterial hypertension (11.5% vs 29.0%, p=0.006) were significantly lower in ANA-negative patients than in the positive group. The proportion of IgG elevation, an indicator of disease activity and severity of inflammation, was significantly lower in the ANA-negative patients than that in the positive group (14.3% vs 41.2%, p<0.001), while no significant differences were found in other inflammatory indicators and skin scores.Conclusion:This study describes the clinical features of SSc patients with negative ANAs, which have been rarely mentioned or focused in existing studies. Antinuclear antibody is proved to be strongly associated with the clinical manifestations of systemic sclerosis patients and ANA-negative SSc patients tend to be in relatively milder conditions, including a less common involvement of critical organs and a more temperate inflammatory severity.References:[1]Seri, Jeong, Dahae, et al. Diagnostic value of screening enzyme immunoassays compared to indirect immunofluorescence for anti-nuclear antibodies in patients with systemic rheumatic diseases: A systematic review and meta-analysis. [J]. Seminars in arthritis and rheumatism, 2018.[2]Hesselstrand, R. The association of antinuclear antibodies with organ involvement and survival in systemic sclerosis[J]. Rheumatology, 2003, 42(4):534-540.[3]Behmanesh F, Amin R, Khajedaluee M, et al. Autoantibody Profile in Systemic Sclerosis[J]. Acta Medica Iranica, 2010, 48(1):12-20.[4]Hachulla E, Dubucquoi S. Nuclear auto-antibodies: a useful tool for the diagnosis, the classification and the prognosis of systemic sclerosis. [J]. La Revue de Médecine Interne, 2004, 25(6):442-447.Disclosure of Interests:None declared

Anti-RNA Polymerase III Antibody Prevalence and Associated Clinical Manifestations in a Large Series of French Patients with Systemic Sclerosis: A Cross-sectional Study

2009 ◽  
Vol 37 (1) ◽  
pp. 125-130 ◽  
Author(s):  
OLIVIER MEYER ◽  
LUC DE CHAISEMARTIN ◽  
PASCALE NICAISE-ROLAND ◽  
JEAN CABANE ◽  
FLORENCE TUBACH ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Topoisomerase I ◽  
Rna Polymerase Iii ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
The United States ◽  
Cutaneous Disease ◽  
Polymerase Iii ◽  
Renal Crisis

Objective.To determine the prevalence of anti-RNA polymerase III autoantibodies in French patients with systemic sclerosis (SSc) and to identify the associated clinical manifestations.Methods.Consecutive patients with SSc seen in 3 tertiary centers in Paris were included. Sera samples were collected together with the relevant clinical and immunological data. Anti-RNA polymerase III antibodies were detected by ELISA at a central laboratory. Data on other antibodies were abstracted from the medical records.Results.We included 319 patients: 84% women, 36% with a diffuse cutaneous subtype, 44% with pulmonary fibrosis, 5% with pulmonary hypertension, 4% with renal crisis, among whom 29 (9.4%) had anti-RNA polymerase III antibodies. These antibodies were more prevalent in patients with diffuse than with limited cutaneous disease (14.3% vs 6.0%; OR 2.6, 95% CI 1.2–5.48, p = 0.016). Renal crisis was more prevalent in patients with than in those without anti-RNA polymerase III antibodies (14% vs 3%; OR 5.0, 95% CI 1.4–17.3, p = 0.012). Renal crisis occurred in 2.2% of patients with anti-topoisomerase I and 3.9% of patients with anticentromere antibodies. Of the patients with anti-RNA polymerase III antibodies, 24 (83%) had no other systemic sclerosis-specific autoantibodies.Conclusion.The prevalence of anti-RNA polymerase III antibodies in French patients appeared to be lower than in the United States and similar to that in continental Europe. These antibodies were consistently associated with diffuse cutaneous disease and were the most common immunological marker for renal crisis. Anti-RNA polymerase III determination can help to risk-stratify SSc patients at high risk for this severe manifestation.

scholarly journals OP0249 SERUM PROTEOMIC BIOMARKERS DEFINE PATIENTS WITH SYSTEMIC SCLEROSIS WITH INTERSTITIAL LUNG DISEASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 152.2-152
Author(s):  
M. De Santis ◽  
N. Isailovic ◽  
A. Ceribelli ◽  
F. Motta ◽  
M. Vecellio ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Proteomic Analysis ◽  
Organ Involvement ◽  
High Morbidity ◽  
Healthy Controls ◽  
Altered Expression ◽  
Calgranulin B ◽  
Angiopoietin 2

Background:Systemic sclerosis (SSc) is a systemic condition affecting multiple organs and thus being burdened by high morbidity and mortality; disease management is based largely on the early detection of organ involvement, particularly in the case of interstitial lung disease (ILD), ideally through noninvasive biomarkers. Beside serum autoantibodies associated with diffuse SSc, there is currently no reliable serum marker to predict the onset of SSc organ involvement, monitor its progression, and foresee the response to treatments. Proteomic analysis based on aptamer technology is a powerful method with the potential to address this unmet need in SSc.Objectives:To identify serum biomarkers associated with ILD in SSc.Methods:Serum samples from 6 women with SSc (3 with ILD at high-resolution pulmonary CT scan) and 7 age-matched female healthy controls (HC) were analyzed using the SOMAscan platform (SomaLogic, Inc., Boulder, CO, USA) to test more than 1300 proteins even at femtomolar concentration. Subsequent validation of candidate proteins was performed using ELISA in an independent cohort of 88 patients with SSc and 48 HC. Statistical analysis included Student’s t-test and was assessed using the SomaSuite software (SomaLogic, Boulder, CO, USA).Results:The proteomic analysis identified 33 proteins with significantly different serum levels in SSc cases compared to HC and 9 proteins differentiating SSc patients according to ILD (Table 1). Compared to HC, SSc sera manifested an altered expression of proteins involved in extracellular matrix formation and cell-cell adhesion (with higher Calpain, EphA5, IDS, MATN2, MMP-12, TNR4, and lower desmoglein-1, SNP25), angiogenesis (with higher anti-angiogenetic factors as angiopoietin-2 and kininogen high molecular weight) lymphocyte recruitment, activation, and signaling (with higher CXCL-1, LAG3 and lower SH21A) with an overall inhibition of neutrophil function (with lower G-CSF-R, CD177, calgranulin B).Table 1.Significantly altered proteins at serum proteomic analysis of systemic sclerosis (SSc) with or without interstitial lung disease (ILD) and healthy controls (HC)SSc versus healthy controlsSSc with ILD versus SSc without ILD and healthy controlsIncreasedReducedIncreasedReducedAldolase AAngiopoietin-2*C1QR1CalpainCOLEC12 EotaxinEphA5Fractalkine/CXCL-1GranulinsIDS Kininogen, HMVLAG-3Lamin-B1LRP1bMATN2MMP-12STAT1 TMR4AdrenomedullinASGR1C1sC5Calgranulin BCD177Desmoglein-1Flt-3 ligandG-CFS-RIL-1RaLeptinLypd3SH21ASNP25TPBS2FCRL3IL-22BP**MCP-3PDE11PGP9.5sICAM-5StratifinBAFFDERM*significantly increased also at ELISA** significantly increased at ELISA only in SSc with ILD versus HCThe majority of proteins with higher levels in SSc with ILD compared to SSc without ILD were involved in intracellular signaling and cell cycle (FCRL3, PDE11, Stratifin), along with higher MCP-3, a monocyte chemoattractant, and sICAM-5, ligand for the leukocyte adhesion protein LFA-1. Of note, we found that increased IL-22BP, antagonist of IL-22, and decreased BAFF levels characterized SSc with ILD.Conclusion:Aptamer proteomic analysis allowed to define serum profiles differentiating SSc patients from healthy controls and SSc with ILD from SSc without ILD; the proteins identified are involved in SSc pathogenic pathways and after further investigation on larger cohorts they can be used as reliable biomarkers.Characters from table content including title and footnotes: 631Disclosure of Interests:None declared

scholarly journals AB0451 TO EVALUATE THE PREVALENCE OF INTERSTITIAL LUNG DISEASE (ILD) AND/OR PULMONARY ARTERIAL HYPERTENSION (PAH) IN PATIENTS AFFECTED BY SYSTEMIC SCLEROSIS (SSC) AND TO DETERMINE THE FACTORS ASSOCIATED WITH ILD

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1253.1-1253
Author(s):  
R. Ortega Castro ◽  
R. Mariscal-Ocaña ◽  
M. Rojas-Giménez ◽  
J. Calvo Gutierrez ◽  
A. Escudero Contreras ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Topoisomerase I ◽  
Systolic Pressure ◽  
University Hospital ◽  
Pulmonary Artery Systolic Pressure ◽  
Skin Involvement ◽  
Factors Associated ◽  
Anticentromere Antibodies

Background:Systemic sclerosis (SSc) is a chronic autoimmune disease that carries significant mortality. Despite diagnostic and therapeutic advances in recent years, there is still a significant percentage of patients who do not present a complete clinical response, with the associated increase in morbidity and mortality. Specifically, pulmonary disease is frequent and entails a poor prognosis, with interstitial lung disease (ILD) and pulmonary hypertension (PAH) being the two most important complications, the first and second cause of mortality, respectively.Objectives:To evaluate the prevalence of ILD and/or PAH in patients affected by SSc and to determine the factors associated with ILD.Methods:Cross-sectional observational study of 102 patients diagnosed with SSc (Limited, Diffuse, SSc without scleroderma or Pre-scleroderma), treated between 1975 and 2020 at the Reina Sofia University Hospital in Cordoba. A descriptive study of the cohort was carried out and factors independently associated with ILD were evaluated using a multiple logistic regression model.Results:102 patients were included, 87.3% of these were female with an average age of 50.8 (14) years. There were 20 deaths (19.8%), from which 55% died because of SSc and the main reason was ILD and/or PAH. Respiratory complications (as ILD or as PAH) were present in 59 patients (57.8%), of whom 52 were diagnosed with ILD (90.4% with a pattern of non-specific interstitial pneumonia) and 25 PAH, whose mean pulmonary artery systolic pressure was 47.16 (18.54) mmHg. Anti-topoisomerase I antibodies were positive in 34.6% of patients who developed ILD, while anticentromere antibodies were more frequent in SSc without interstitial lung disease (80%). Independent factors associated with ILD were type of SSc, proximal skin involvement, anticentromere antibodies, current treatment with corticoids and the death.Conclusion:Just over half of the patients with SSc have lung disease (as ILD or as PAH). The main risk factors associated with ILD are proximal skin involvement and treatment with glucocorticoids, probably in the context of more severe forms that require more treatment. Anticentromere antibodies are more prevalent in patients with Limited SSc and their expression decreases the risk of developing ILD in these patients.References:[1]Orlandi M, Barsotti S, Lepri G, et al. Clin Exp Rheumatol 2018 Jul-Aug; 36 Suppl 113: 3-23[2]Hao Y, Hudson M, Baron M, et al. Arthritis Rheumatol. 2017;69(5):1067-1077.[3]Furue M, Mitoma C, Mitoma H, et al. Immunol Res. 2017 Aug; 65: 790-7.[4]Nihtyanova SI, Schreiber BE, Ong VH, et al. Arthritis Rheumatol. 2014 Jun; 66: 1625-35.Disclosure of Interests:None declared.

Sign in / Sign up

Export Citation Format

Share Document