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 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 Functionally Active Antibodies to the Angiotensin II Type 1-Receptor Measured by a Luminometric Bioassay Do Not Correlate With Clinical Manifestations in Systemic Sclerosis: A Comparison With Antibodies to Vascular Receptors and Topoisomerase I Detected by ELISA

2021 ◽  
Vol 12 ◽  
Author(s):  
Lukas Bankamp ◽  
Beate Preuß ◽  
Ann-Christin Pecher ◽  
Nicola Beucke ◽  
Jörg Henes ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Angiotensin Ii ◽  
Liver Diseases ◽  
Topoisomerase I ◽  
Clinical Manifestations ◽  
Digital Ulcers ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Organ Manifestations

Objectives1) To detect functionally active antibodies(abs) to the angiotensin II type-1-receptor (AT1R) by a novel luminometric assay. 2) To assess their prevalence in systemic sclerosis (SSc), other collagen disorders, as well as in further chronic inflammatory disorders including autoimmune, toxic and chronic viral diseases. 3) To compare these abs with anti-AT1R antibodies by ELISA as well as with antibodies to endothelin-type-A receptors (ETA1) and to topoisomerase I (topo-I) with respect to their specificity and clinical relevance.MethodsSera from 98 SSc-patients, 110 patients with other chronic inflammatory rheumatic disorders, 97 patients with autoimmune liver diseases, 57 patients with toxic or chronic viral liver diseases and 36 healthy controls were analyzed. A luminometric bioassay was established with Huh-7-cells constitutively expressing the AT1R. Patients’ sera were also tested by commercially available ELISA for anti-AT1R, -ETA1- and by an in-house ELISA for anti–topo-I-abs.ResultsFifty-two percent of the SSc-patients had functionally active anti-AT1R-abs with stimulatory (34%) or inhibitory capacity (18%). They were present also in up to 59% of patients with other rheumatic diseases but only 22% of healthy individuals (sensitivity 52%, specificity 53%). The functionally active antibodies detected by the luminometric assay did not correlate with anti-AT1R-, -ETA1- or -topo-I-abs measured by ELISA, but there was a strong correlation between anti-topo-I-, AT1R-, and -ETA1-ab reactivity measured by ELISA. Sensitivities of 55%, 28% and 47% and specificities of 66%, 87%, and 99% were calculated for these anti-AT1R-, -ETA1-, and anti-topo-I-abs, respectively. Functionally active abs did not correlate with disease severity or any organ manifestation. In contrast, abs to topo-I, AT1R, and ETA1 were associated with digital ulcers, pulmonary- and esophageal manifestation.ConclusionsFunctionally active anti-AT1R-abs can be detected in SSc-patients but do not correlate with disease activity. They are not specific for this disease and occur also in other autoimmune disorders and even viral or toxic diseases. Also, the vascular antibodies detected by ELISA are not SSc-specific but correlated with disease manifestations. In contrast, anti-topo-I-abs were confirmed to be a highly specific biomarker for both, diagnosis and organ manifestations of SSc.

scholarly journals Increased Frequency of Activated Switched Memory B Cells and Its Association With the Presence of Pulmonary Fibrosis in Diffuse Cutaneous Systemic Sclerosis Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Diána Simon ◽  
Péter Balogh ◽  
Szabina Erdő-Bonyár ◽  
Katalin Böröcz ◽  
Tünde Minier ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
B Cells ◽  
Pulmonary Fibrosis ◽  
B Cell ◽  
Topoisomerase I ◽  
Citrate Synthase ◽  
Severe Form ◽  
Memory B Cells ◽  
Autoantibody Production ◽  
B Cell Subsets

Disease-associated, high-affinity pathological autoantibody production is a well-described consequence of immune dysregulation affecting B cells in systemic sclerosis (SSc), including the distribution of B-cell subsets. We have previously shown that the increased relative frequency of CD19+CD27+IgD− switched memory B cells is associated with the severe form of SSc. This study sought to analyze memory B cell subsets using an extended range of markers for further subdivision based on CD19, IgD, CD27, CD38 and CD95 phenotype, to define relationship between the alterations of memory B cell subsets and the clinical features of SSc. Peripheral blood samples were obtained from 21 SSc patients, including 14 diffuse (dcSSc) and 7 limited (lcSSc) cutaneous SSc patients, with disease duration of 2.7 ( ± 1.6) years. After purification of CD19+ B cells, multiparametric flow cytometry was performed and the frequencies of CD19+IgD−CD27−CD38+ double negative (DN) 1, CD19+IgDloCD27+CD38+ unswitched, CD19+IgD−CD27+CD38+CD95− resting switched and CD19+IgD−CD27+CD38−CD95+ activated switched memory (ASM) B cells were determined, and correlated with clinical features of SSc. The dcSSc patients had a higher frequency of ASM B cells (p = 0.028) compared to lcSSc patients. The percentage of ASM B cells was elevated in anti-Scl-70 (anti-topoisomerase I) antibody positive patients compared to negative patients (p = 0.016). Additionally, the frequency of ASM B cells was also increased in patients with pulmonary fibrosis (p = 0.003) suggesting that patients with severe form of SSc have higher ASM B cell ratios. Furthermore, the ratio of DN1 B cells was decreased (p = 0.029), while the level of anti-citrate synthase IgG natural autoantibody was elevated (p = 0.028) in patients with active disease. Our observations on the increase of ASM B cells in dcSSc and in patients with pulmonary fibrosis may point to the association of this alteration with the severe form of the disease. Functionally the correlation of ASM B cells as effector memory-plasma cell precursors with anti-topoisomerase I antibody positivity could reflect their contribution to pathological autoantibody production, whereas the decrease of memory precursor DN B cells and the increase of anti-citrate synthase IgG autoantibody may have potential significance in the assessment of disease activity.

B-Cell Epitope Mapping of DNA Topoisomerase I Defines Epitopes Strongly Associated with Pulmonary Fibrosis in Systemic Sclerosis

2000 ◽  
Vol 22 (3) ◽  
pp. 344-351 ◽  
Author(s):  
Catherine Rizou ◽  
John P. A. Ioannidis ◽  
Evgenia Panou-Pomonis ◽  
Maria Sakarellos-Daitsiotis ◽  
Constantinos Sakarellos ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Fibrosis ◽  
B Cell ◽  
Topoisomerase I ◽  
Epitope Mapping ◽  
Cell Epitope ◽  
Dna Topoisomerase I ◽  
Dna Topoisomerase ◽  
B Cell Epitope

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

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