Autoantibodies against Endothelin 1 Type A Receptor Are Strong Predictors of Digital Ulcers in Systemic Sclerosis

2015 ◽  
Vol 42 (10) ◽  
pp. 1801-1807 ◽  
Author(s):  
Jérôme Avouac ◽  
Gabriela Riemekasten ◽  
Christophe Meune ◽  
Barbara Ruiz ◽  
André Kahan ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Type A ◽  
Digital Ulcers ◽  
Clinical Predictors ◽  
Endothelin 1 ◽  
History Of ◽  
Angiogenic Markers ◽  
Cox Analysis ◽  
Or History

Objective.To determine the predictive value of functional autoantibodies against vascular receptors for the development of ischemic digital ulcers (DU) in patients with systemic sclerosis (SSc).Methods.Angiotensin II Type 1 receptor (AT1R) and endothelin 1 Type A receptor (ETAR) autoantibodies were measured at baseline in a prospective cohort of 90 patients with SSc together with 5 validated angiogenic markers. The primary outcome was the occurrence of at least 1 new ischemic DU during the 5-year followup.Results.Twenty-four patients developed at least 1 new DU during the followup period. Univariate Cox analysis revealed that concentrations above the median value of anti-AT1R and anti-ETAR antibodies were predictive of the occurrence of ischemic DU (HR 2.85, 95% CI 1.19–6.84 and HR 3.39, 95% CI 1.35–8.50, respectively). A first multivariate Cox analysis including functional autoantibodies and clinical predictors of new DU confirmed anti-ETAR autoantibodies as independent predictors of the occurrence of new ischemic DU (HR 3.15, 95% CI 1.22–8.13) together with a history of DU at baseline. In a second model implemented with angiogenic markers, anti-ETAR autoantibodies remained an independent predictor of the occurrence of new ischemic DU (HR 9.59, 95% CI 1.75–52.64) together with the presence at baseline of active DU or history of DU.Conclusion.Anti-ETAR autoantibodies can be used together with the presence of current or past DU to identify patients with SSc who are at risk for the development of subsequent DU. These autoantibodies may allow for earlier management and therapeutic intervention.

scholarly journals AB0450 PERIPHERAL MACROVASCULAR INVOLVEMENT IN SYSTEMIC SCLEROSIS AS COMPARED WITH HEALTHY CONTROLS: A SMALL COHORT STUDY BY COLOR AND SPECTRAL DOPPLER ULTRASONOGRAPHY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1252.2-1252
Author(s):  
R. D’alessandro ◽  
E. Garcia Gonzales ◽  
P. Falsetti ◽  
C. Baldi ◽  
F. Bellisai ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Clinical Features ◽  
Doppler Ultrasonography ◽  
Power Doppler ◽  
Ulnar Artery ◽  
Artery Occlusion ◽  
Power Doppler Ultrasonography ◽  
Digital Ulcers ◽  
Healthy Controls ◽  
History Of

Background:Together with autoimmune-inflammation and fibrosis, microvasculopathy is a hallmark of SSc. However, also macrovascular changes may occur including peripheral proliferative vasculopathy. Whether this changes may represent a specific SSc marker with a predictive value remains a matter of debate.[1,2,3]Objectives:To study peripheral macrovascular involvement by color doppler ultrasound (CDUS) with spectral wave analysis (SWA) in a cohort of 40 SSc patients as compared to healthy controls. To further analyze any differences among the SSc population.Methods:Forty SSc patients and 36 healthy controls were examined by CDUS with SWA of both hands. Macrovascular involvement was assessed by measuring the resistivity index (RI) of distal ulnar and radial arteries. Examinations were performed with an Esaote MyLab Twice machine equipped with a linear 10-22 MHz probe. Ultrasound examination was carried out by two independent rheumatologists blinded to clinical conditions of the patients. Statistical analysis was performed by using MaxStat software.Results:The RI index resulted increased in the SSc cohort as compared with healthy controls (left ulnar RI 0.977 vs 0.715; right ulnar RI 0.996 vs 0.699; left radial RI 0.988 vs 0.706; right radial RI 0.999 vs 0.688; p<0.001). SSc patients with an increased RI in one artery were more probable to have an increased RI in the other vessels too (r 2 = 0.35; p<0.01). In addition, 8 out of 40 SSc patients presented left ulnar artery occlusion (UAO) and 7 out of 40 SSc patients presented right UAO, of which 6 presented bilateral UAO. Awaiting to enlarge the cohort for further analysis, descriptive data regarding increased RI at CDUS/SWA and clinical features, including years from onset of the disease, subtype of SSc, mRSS, history of digital ulcers, interstitial lung disease and PAH are described in Table 1.Conclusion:Peripheral macrovascular involvement was observed in SSc patients as compared with healthy controls. Further studies will determine whether this feature may have specificity for diagnosis/prognosis in SSc.References:[1]Lescoat A, Yelnik CM, Coiffier G et al. Ulnar Artery Occlusion and Severity Markers of Vasculopathy in Systemic Sclerosis: A Multicenter Cross-Sectional Study. Arthritis Rheumatol. 2019;71:983-990.[2]Lescoat A, Coiffier G, Rouil A et al. Vascular Evaluation of the Hand by Power Doppler Ultrasonography and New Predictive Markers of Ischemic Digital Ulcers in Systemic Sclerosis: Results of a Prospective Pilot Study. Arthritis Care Res (Hoboken). 2017;69:543-551.[3]Schioppo T, Orenti A, Boracchi P, De Lucia O, Murgo A, Ingegnoli F. Evidence of macro- and micro-angiopathy in scleroderma: An integrated approach combining 22-MHz power Doppler ultrasonography and video-capillaroscopy. Microvasc Res. 2019;122:125-130.Table 1.Main clinical features of the SSc cohort (n=40) studied by CDUS for macrovascular involvement.SSc cohort (n = 40)Years from onsetrange (35 y – 0 y)mean = 10.5 yAutoantibodiesACA 13/40Anti-TopoI 14/40Other 13/40mRSSrange (0 -30)mean = 3ILD17/40PAH7/40Capillaroscopy patternEarly 10/40Active 11/40Late 6/40History of digital ulcers16/40Left ulnar IR0.977Left radial IR0.988Right ulnar IR0.996Right radial IR0.999Disclosure of Interests:None declared.

High D-dimer plasma concentration in systemic sclerosis patients: Prevalence and association with vascular complications

2020 ◽  
pp. 239719832095755
Author(s):  
Sofia Furtado ◽  
Bertrand Dunogué ◽  
Georges Jourdi ◽  
Benjamin Chaigne ◽  
Aziza Chibah ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Plasma Concentration ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Macrovascular Complications ◽  
Digital Ulcers ◽  
Tertiary Referral Center ◽  
History Of ◽  
Diffuse Cutaneous Systemic Sclerosis ◽  
D Dimer

Objective: To determine the frequency of elevated D-dimer plasma concentration (>500 ng/mL) in patients with systemic sclerosis and evaluate its association with systemic sclerosis–specific microvascular and macrovascular complications. Methods: Retrospective observational study of patients with systemic sclerosis followed in a tertiary referral center with at least one measurement of D-dimer between 2010 and 2018. Results: A total of 214 patients were analyzed. Mean age at inclusion was 55.1 ± 14.7 years; 180 (84.1%) were female; 74 (34.6%) had diffuse cutaneous systemic sclerosis. Anti-Scl70 and anti-centromere antibodies were positive in 74 (34.6%) and 75 (35.0%) patients, respectively. D-dimer level was elevated in 93 (43.5%) patients, independently of cutaneous subtype (44.6% in diffuse cutaneous systemic sclerosis vs 42.9% in limited cutaneous systemic sclerosis, p = 0.81). At least one microvascular complication was found in 108 (50.5%) patients: 105 (49.1%) with previous or current digital ulcers, 6 (2.8%) with renal crisis, and 4 (1.9%) with pulmonary arterial hypertension. Microvascular complications were more frequent in patients with elevated D-dimer (57.0% vs 45.5%, p = 0.09), significantly so after exclusion of patients with a history of cancer and/or venous thromboembolism (60.5% vs 44.8%, p = 0.04). Macrovascular complications were detected in 15 (7.0%) patients and were associated with a high D-dimer level (11.8% vs 3.3%, p = 0.03). Over a median follow-up of 2.3 years [1.1–3.3] after D-dimer measurement, new macrovascular complications occurred only in patients with high D-dimer (n = 8). Conclusion: High D-dimer levels are frequently found in systemic sclerosis patients and seem to be associated with the occurrence of macrovascular and microvascular complications after adjustment for confounding factors.

Digital Amputation in Systemic Sclerosis: Prevalence and Clinical Associations. A Retrospective Longitudinal Study

2012 ◽  
Vol 39 (8) ◽  
pp. 1648-1653 ◽  
Author(s):  
PAOLA CARAMASCHI ◽  
DOMENICO BIASI ◽  
CRISTIAN CAIMMI ◽  
GIOVANNI BARAUSSE ◽  
DANIA SABBAGH ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Peripheral Artery Disease ◽  
Disease Duration ◽  
Preventive Strategy ◽  
Digital Ulcers ◽  
Peripheral Artery ◽  
Rheumatology Unit ◽  
History Of ◽  
Artery Disease ◽  
Digital Amputation

Objective.To evaluate the prevalence of digital necrosis requiring surgical amputation in a single-center group of patients with systemic sclerosis (SSc) and to compare the characteristics of patients with and those without this severe complication.Methods.We reviewed the medical records of 188 patients with SSc [162 women, 26 men, mean age 59.2 yrs, mean disease duration 8.0 yrs, mean time from onset of Raynaud’s phenomenon (RP) 11.7 yrs, median followup duration 92 mo] enrolled in the Rheumatology Unit since 2004. Demographic and clinical features were collected, as well as the presence of the typical risk factors for atherosclerosis.Results.Nine patients (4.8%) underwent partial or total surgical digital amputation because of necrotic process; all these patients except 1 had a long history of multiple and persisting digital ulcers. All 9 patients had concomitant large-vessel involvement. Comparison of cases with and without digital amputation showed that this complication was associated with older age, long history of RP, long disease duration, presence of anticentromere antibody, and coexistence of peripheral artery disease and hypercholesterolemia.Discussion.We noted that 4.8% of patients with SSc underwent digital amputation. Our retrospective analysis suggests that peripheral artery disease is strongly associated with digital amputation. The preventive strategy for digital ulcers and amputation associated with SSc should include an extensive diagnostic and preventive investigation for peripheral atherosclerosis.

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 Functional Bowel Disorders in Patients with Brugada Syndrome and Drug-Induced Type 1 Brugada Pattern

2020 ◽  
Author(s):  
Anil Sarica ◽  
Serhat Bor ◽  
Mehmet Orman ◽  
Hector Barajas-Martinez ◽  
Jimmy Juang ◽  
...  
Keyword(s):  
Brugada Syndrome ◽  
Control Group ◽  
Functional Bowel Disorders ◽  
Drug Induced ◽  
Co Morbidity ◽  
History Of ◽  
Bowel Disorders ◽  
Or History ◽  
Brugada Pattern

Introduction: Irritable bowel syndrome (IBS) is one of the most widely recognized functional bowel disorders (FBDs) with a genetic component. SCN5A gene and SCN1B loci have been identified in population-based IBS cohorts and proposed to have a mechanistic role in the pathophysiology of IBS. These same genes have been associated with Brugada syndrome (BrS). The present study examines the hypothesis that these two inherited syndromes are linked. Methods and Results: Prevalence of FBDs over a 12 months period were compared between probands with BrS/drug-induced type 1 Brugada pattern (DI-Type1 BrP) (n=148) and a control group (n=124) matched for age, female sex, presence of arrhythmia and co-morbid conditions. SCN5A/SCN1B genes were screened in 88 patients. Prevalence of IBS was 25% in patients with BrS/DI-Type1 BrP and 8.1% in the control group (p=2.34×10−4). On stepwise logistic regression analysis, presence of current and/or history of migraine (OR of 2.75; 95% CI: 1.08 to 6.98; p=0.033) was a predictor of underlying BrS/DI-Type1 BrP among patients with FBDs. We identified 8 putative SCN5A/SCN1B variants in 7 (12.3%) patients with BrS/DI-Type1 BrP and 1 (3.2%) patient in control group. Five out of 8 (62.5%) patients with SCN5A/SCN1B variants had FBDs. Conclusion: IBS is a common co-morbidity in patients with BrS/DI-Type1 BrP. Presence of current and/or history of migraine is a predictor of underlying BrS/DI-Type1 BrP among patients with FBDs. Frequent co-existence of IBS and BrS/DI-Type1 BrP necessitates cautious use of certain drugs among the therapeutic options for IBS that are known to exacerbate the Brugada phenotype.

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