Leveraging Transfer Learning and Monte Carlo Dropout for Uncertainty Informed NIRS-based Detection of Systemic Sclerosis Hand Perfusion Patterns.

BackgroundEndothelial dysfunction is a key feature of Systemic sclerosis (SSc). MicroRNAs (miRs) are novel post-transcriptional regulators implicated in SSc pathogenesis. MiR-34a and miR-155 are related to endothelial senescence and inflammation.ObjectivesTo...

Background and ObjectivesMicroRNAs (miRs) are a novel class of post-transcriptional regulators that have been implicated in the pathogenesis of Systemic sclerosis (SSc). MiR-34a and miR-155 were found to be related...

Primary biliary cholangitis (PBC) is a cholestatic autoimmune disease and is often associated with systemic sclerosis (SSc). The prevalence of SSc in PBC patients ranges from 1-22% and the diagnosis is often delayed. The aim of this study was to evaluate the role of nailfold capillaroscopy (NFC) for early SSc diagnosis in PBC patients. In this monocentric, cross-sectional study, NFC was performed in 56 PBC patients. Raynaud's phenomenon (RP) was assessed in each patient. Patients with major NFC abnormalities and those with a scleroderma pattern were screened for SSc-specific antibodies. The SSc diagnosis was established using the 2013 American College of Rheumatology and European League Against Rheumatism (ACR/AULAR) and Very Early Diagnosis Of Systemic Sclerosis (VEDOSS) criteria. NFC abnormalities were found in 31 patients (55%): 11 (20%) presented minor abnormalities, 17 (30%) had major abnormalities and 3 (5%) presented a scleroderma pattern. RP was found in 12 patients. Two patients with a scleroderma pattern were newly diagnosed with SSc. All patients newly diagnosed with SSc presented RP. No patient without RP was diagnosed with SSc. Performing NFC in PBC patients can help anticipate the SSc diagnosis. RP should always be checked in PBC patients and should be an indication to perform NFC for early SSc diagnosis. A diagnostic algorithm is proposed.

BackgroundMany systemic sclerosis (SSc) patients develop interstitial lung disease (ILD) during the course of the disease. Promising data have recently shown that lung ultrasound (LUS) is able to detect ILD...

BackgroundEndothelial dysfunction is a key feature of systemic sclerosis (SSc) and the involvement of the microvasculature is one of the earliest features of the disease. Recent new criteria for very...

ObjectivesThe EULAR (European League Against Rheumatism) Scleroderma Trials and Research Group (EUSTAR) has identified preliminary criteria for very early diagnosis of systemic sclerosis (SSc). Our aim was to assess the...

Chemokine (C-X-C motif) ligand 4 (CXCL4) is a biomarker of unfavorable prognosis in Systemic Sclerosis (SSc), a potentially severe autoimmune condition, characterized by vasculitis, fibrosis and interferon (IFN)-I-signature. We recently reported that autoantibodies to CXCL4 circulate in SSc patients and correlate with IFN-α. Here, we used shorter versions of CXCL4 and CXCL4-L1, the CXCL4 non-allelic variant, to search for autoantibodies exclusively reacting to one or the other CXCL4 form. Moreover, to address whether anti-CXCL4/CXCL4-L1 antibodies were present before SSc onset and predicted SSc-progression, we longitudinally studied two VEDOSS (Very Early Diagnosis of Systemic Sclerosis) patient cohorts, separating SSc-progressors from SSc-non-progressors. We found that anti-CXCL4-specific autoantibodies were present in both SSc and VEDOSS patients (both SSc-progressors and SSc-non-progressors). Anti-CXCL4-L1-specific autoantibodies were especially detected in long-standing SSc (lsSSc). Anti-CXCL4/CXCL4-L1 antibodies correlated with IFN-α and with specific SSc-skin features but only in lsSSc and not in early SSc (eaSSc) or VEDOSS. Thus, a broader antibody response, with reactivity spreading to CXCL4-L1, is characteristic of lsSSc. The early anti-CXCL4 autoantibody response seems qualitatively different from, and likely less pathogenic than, that observed in advanced SSc. Lastly, we confirm that anti-CXCL4 autoantibodies are SSc-biomarkers and uncover that also CXCL4-L1 becomes an autoantigen in lsSSc.

Background Although some dated studies suggest a possible association between clinical characteristics and isotypes of anticentromere antibodies (ACA) in patients with systemic sclerosis (SSc), characteristics of ACA have not been described thoroughly in SSc. Objectives Describe characteristics of anticentromere antibody (ACA) response in a large cohort of SSc patients. Evaluate differences between ACA response between SSc patients fulfilling ACR 2013 criteria and those with very early diagnosis of SSc (VEDOSS). Methods ACA IgG, IgM and IgA levels were assessed in serum samples of patients visiting the Leiden SSc care pathway and who were IgG ACA+ at baseline. Patients had to fulfil either the ACR criteria or the VEDOSS criteria. Differences in isotype expression and levels between the two groups were evaluated, also with stratification for disease duration. Furthermore, in the SSc group we determined correlations between isotypes and disease duration and evaluated if isotype positivity was associated with clinical manifestations. Results ACA characteristics were measured in 167 ACA IgG+ patients. Thirty-five patients (21%) fulfilled the VEDOSS criteria and 132 (79%) the ACR criteria. ACA IgG+ patients displayed a broad isotype usage with 75% being ACA IgA+ and 68% being ACA IgM+ in serum. Patients within the SSc group showed higher ACA IgG levels and a higher percentage of ACA IgM positivity compared to the VEDOSS patients. Notably, these findings remained valid after stratification for disease duration, demonstrating that VEDOSS patients that did not progress to SSc within at least 5 years had lower ACA IgG levels and were less frequently positive for ACA IgM. In the SSc group, moderate correlations between isotypes were found; ACA IgM positivity was associated with occurrence of digital ulcers (p=0.02). Conclusion We observe a clear difference in the quality of the centromere-specific immune response between VEDOSS patients and SSc patients, also when stratifying for disease duration. The higher ACA IgG levels and presence of ACA IgM in SSc patients indicates that the ACA response in SSc is more pronounced showing signs of ongoing activity. These data indicate that the ACA B cell response is potentially relevant in disease development. In addition, ACA isotype expression and ACA IgG levels might contribute to better identify VEDOSS patients at risk for SSc development. Disclosure of Interests Nina van Leeuwen: None declared, Maaike Boonstra: None declared, Jaap Bakker: None declared, Corrie Wortel: None declared, Hans Ulrich Scherer Grant/research support from: Sanofi, BMS, Rene Toes Grant/research support from: Sanofi, Thomas Huizinga Consultant for: Merck, UCB, Bristol Myers Squibb, Biotest AG, Pfizer, GSK, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience Inc., Nycomed, Boeringher, Takeda, Zydus, Epirus, Eli Lilly, Jeska de Vries-Bouwstra: None declared

BackgroundFibrosis and vasculopathy are the major concerns in systemic sclerosis (SSc), the pathogenesis of which is not clear. Lysyl oxidase (LOX) is an extracellular copper enzyme that cross-links collagen and...

Characteristics of Swiss patients with systemic sclerosis have not been described so far. The aim of the current study was to identify unmet needs in comparison with other European countries that could inform specific interventions to improve the care of systemic sclerosis patients. We analysed Swiss and other European systemic sclerosis patients registered in European Scleroderma Trials And Research (EUSTAR) and the Very Early Diagnosis Of Systemic Sclerosis (VEDOSS) cohort. Demographics, clinical profiles, organ involvement and survival of established, early/mild and very early / very mild systemic sclerosis patients were described and compared between the cohorts. We included 679 Swiss and 8793 European systemic sclerosis patients in the analysis. Over 95% of patients in both cohorts were Caucasian, disease subsets were similar, and no age difference was found. The Swiss cohort had more male patients (25% vs 16% European, p = 0.005) and higher prevalence of early/mild and very early / very mild patients (26.1 vs 8.5% European and 14.9% vs 6.7% European, respectively, both p <0.0001). Disease duration in established systemic sclerosis patients at first presentation was numerically shorter but not significant in the Swiss cohort: 5.0 years (1–12) Swiss vs 6.0 years (2–12) years European, p = 0.055). Despite the earlier referral of Swiss patients to systemic sclerosis expert centres, they showed evidence of more severe disease, particularly in the limited cutaneous systemic sclerosis subset, but no differences in overall survival on longitudinal follow-up were observed. This is the first report of the national Swiss EUSTAR cohort. It identifies earlier referral to systemic sclerosis expert centres, before major organ damage occurs, and when outcome can still be modified, as a priority to improve care of patients with systemic sclerosis.

Background:Systemic sclerosis (SSc) is characterized by progressive fibrosis and microvascular dysfunction that involves multiple organ systems, including kidneys. Kidney involvement, beyond the scleroderma renal crisis (SRC), is often asymptomatic and...

Background:primary heart involvement (pHI) is frequent in systemic sclerosis (SSc) and it is associated with a bad prognosis; early recognition is therefore essential. Cardiac magnetic resonance (CMR) represents the non-invasive...

BackgroundGastrointestinal tract (GIT) is often involved in Systemic Sclerosis (SSc), even in the very early diagnosis of SSc (VEDOSS). In SSc, the oesophagus is mainly involved, followed by the anorectum:...

Background:Systemic sclerosis (SSc) is a rare and progressive autoimmune disease, whose diagnosis is difficult in the early stages because of the lack of specific signs and symptoms. Criteria for a...

Background Recognizing systemic sclerosis (SSc) in patients without cutaneous involvement is a real challenge due to inapparent clinical picture. 1980 ACR classification criteria for SSc fail to verify the diagnosis in the majority of cases. Therefore, the diagnosis is usually established years and decades after SSc onset at the stage of full-blown visceral disease. Introduction of 2013 ACR/EULAR classification criteria into clinical practice allow early diagnosis of SSc even in cases without skin involvement thanks to the fact, that list of considered criteria includes telangiectasia, pulmonary arterial hypertension (PAH), abnormal nailfold capillaries and SSc-related autoantibodies. Objectives To identify specific features in the clinical course of SSc sine scleroderma (ssSSc) in patients with PAH. Methods 11 patients with verified SSc diagnosis according to 2013 criteria were included; participants did not have any SSc-specific signs of skin involvement, such as puffy fingers, fingers’ skin thickening/induration or skin atrophy. PAH was diagnosed in 11 patients during of right heart catheterization. Results Isolated Raynaud’s phenomenon (RP) was along-standing diagnosis (more than 5 years) in all patients, except for one whoman, in whom the disease manifested with signs of Sjogren’s syndrome (SjS) (parotitis). Benign, chronic, and gradually progressing during a long time disease was documented in all patients. In 7 patients out of 11 SSc diagnosis was initially suspected by cardiologists, and later confirmed by detection of antinuclear autoantibodies. The following signs were documented in SSc patients as initial manifesting non-Raynaud symptoms: esophageal dysmotility – in 3 patients, digital ulcers – in 2, telangiectasia – in 2 patients, and dyspnea (PAH symptom) – in 1 patient. None of the patients ever experienced skin thickening typical for SSc. RP was present in all 100%, but digital ischemic alterations – digital tip ulcers, pitting scars were found only in 3 patients. SSc diagnosis was verified based on abnormal nailfold capillaries (in 100% cases), and based on identification of SSc-specific antibodies (anticentromere antibodies – ACA) – in 7 patients. Anti-Ro-antibodies were found in 4 patients, anti-RNP-70 – in 3. SjS was established in 3 out of 4 anti-Ro-antibodies – positive patients and ruled out in one. Myositis was documented in past-medical history in one patient with anti-RNP-70-antibodies positivity. It should be noted, that 3 ACA-negative patients had, nevertheless, a “threshold” score value (9 scores) for SSc diagnosis, exhibiting many clinical features in favor of SSc diagnosis beyond any doubt. Esophageal dysmotility and associated symptoms were found in 10 out of 11 SSc patients. One patient had an SSc–rheumatoid arthritis overlap syndrome (erosive arthritis, joint deformities, positive ACA, rheumatoid factor, anti-CCP). Conclusion Introduction of 2013 ACR-EULAR classification criteria for SSc into clinical practice was highly relevant for identification of SSc cases without cutaneous involvement, providing therefore a timely diagnosis in this group of patients, and allowing to prognosticate the clinical course of PAH. 2013 ACR-EULAR classification criteria for SSc is an algorithm for SSc verification in patents with PAH, especially in the absence of typical for SSc cutaneous disease. The earlier PAH-SSc is diagnosed and PAH-specific therapy is initiated, the longer will be patient’ lifespan. Disclosure of Interests Natalia Yudkina: None declared, Alexander Volkov : None declared, Ekaterina Nikolaeva: None declared, Ildar Kurmukov: None declared, Evgeny Nasonov Speakers bureau: Pfizer, Inc., MSD, Novartis, AbbVie Inc., Celgen Corporation, Biocad, Janssen, UCB, Inc.