Survival and organ involvement in patients with limited cutaneous systemic sclerosis and anti-topoisomerase-I antibodies: determined by skin subtype or auto-antibody subtype? A long-term follow-up study

Kranenburg, P.; Hombergh, Wieneke M. T. van den; Knaapen-Hans, Hanneke K. A.; Hoogen, F.H.J. van den; Fransen, Jaap; Vonk, Madelon C.

doi:10.1093/rheumatology/kew298

Cited by 36 publications

(28 citation statements)

References 25 publications

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“…Mortality was related to both skin and serologic profile (9). Kranenburg et al also demonstrated that lcSSc patients who were positive for anti-topo I antibodies contrasted with lcSSc patients who were negative for anti-topo I antibodies and dcSSc patients who were positive for anti-topo I antibodies in terms of survival and organ involvement (32). Taken together, those studies suggest that subclassification combining antibody profile and skin involvement might predict clinical outcomes more accurately than skin or serologic features alone (9,32).…”

Section: Discussionmentioning

confidence: 99%

Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis

Sobanski

Giovannelli

Allanore

et al. 2019

Arthritis & Rheumatology

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Objective Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) depending on the extent of skin involvement. This subclassification may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research (EUSTAR) database includes data on a prospective cohort of SSc patients from 122 European referral centers. This study was undertaken to perform a cluster analysis of EUSTAR data to distinguish and characterize homogeneous phenotypes without any a priori assumptions, and to examine survival among the clusters obtained. Methods A total of 11,318 patients were registered in the EUSTAR database, and 6,927 were included in the study. Twenty‐four clinical and serologic variables were used for clustering. Results Clustering analyses provided a first delineation of 2 clusters showing moderate stability. In an exploratory attempt, we further characterized 6 homogeneous groups that differed with regard to their clinical features, autoantibody profile, and mortality. Some groups resembled usual dcSSc or lcSSc prototypes, but others exhibited unique features, such as a majority of lcSSc patients with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival regardless of cutaneous involvement. Conclusion Our findings suggest that restricting subsets of SSc patients to only those based on cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with a distinct prognosis.

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Section: Discussionmentioning

confidence: 99%

Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis

Sobanski

Giovannelli

Allanore

et al. 2019

Arthritis & Rheumatology

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“…Increased levels of ATAs are mainly associated with diffuse cutaneous disease (dcSSc) ( P < 0.0001, OR = 4.26) ( 22 ) and serious organ involvement ( 13 , 24 ). Patients with ATAs had higher SSc-related mortality rate and poor prognosis ( 25 ). ARA presence indicates a high risk of rapidly progressive skin thickening ( P = 0.042, OR = 3.24, 95% CI = 1.44–7.31), and changes in ARA levels may correspond to changes in modified Rodnan skin thickness score ( 26 , 27 ).…”

Section: Classical Disease-specific Autoantibodies In Clinical Manifementioning

confidence: 99%

“…Studies have shown ATA association with a higher probability of interstitial lung disease (ILD) ( P < 0.0001, OR = 4.76, 95% CI = 3.48–6.50), even in ATA-positive patients with lcSSc ( 22 , 25 , 32 ). Recent studies have indicated that ATAs may be related to disability in hand, oral manifestation ( 33 , 34 ), and flexion contractures in metacarpophalangeal and proximal interphalangeal joints ( 35 ), indicating their specificity, to a certain degree, in organ fibrosis.…”

Section: Classical Disease-specific Autoantibodies In Clinical Manifementioning

confidence: 99%

Classical Disease-Specific Autoantibodies in Systemic Sclerosis: Clinical Features, Gene Susceptibility, and Disease Stratification

et al. 2020

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Systemic sclerosis (SSc) is an autoimmune disease characterized by abnormalities in microcirculation, extracellular matrix accumulation, and immune activation. Autoantibodies are markers of immune abnormalities and provide diagnostic and predictive value in SSc. Anti-topoisomerase antibodies (ATAs), anticentromere antibodies (ACAs), and anti-RNA polymerase antibodies (ARAs) are the three classical specific antibodies with the highest availability and stability. In this review, we provide an overview of the recent progress in SSc research with respect to ATAs, ACAs, and ARAs, focusing on their application in distinguishing clinical phenotypes, such as malignancy and organ involvement, identifying genetic background in human leukocyte antigen (HLA) or non-HLA alleles, and their potential roles in disease pathogenesis based on the effects of antigen-antibody binding. We finally summarized the novel analysis using ATAs, ACAs, and ARAs on more detailed disease clusters. Considering these advantages, this review emphasizes that classical SSc-specific autoantibodies are still practical and have the potential for patient and risk stratification with applications in precise medicine for SSc.

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“…By contrast, the dcSSc subset presents a more aggressive progression characterized by severe internal organ manifestations with skin thickening extended proximally to elbows and knees as well as the trunk. In the dcSSc subtype, anti-topoisomerase I autoantibodies (anti-Scl-70) are more frequent, while in the lcSSc subtype, anti-centromere autoantibodies are dominant features (Kranenburg et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Metabolic Pattern of Systemic Sclerosis: Association of Changes in Plasma Concentrations of Amino Acid-Related Compounds With Disease Presentation

Smoleńska

Zabielska-Kaczorowska

Wojteczek

et al. 2020

Front. Mol. Biosci.

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Objective: Amino acids (AA) and their derivatives play an integral role in the synthesis of structural and regulatory elements in human organisms and therefore pathologies such as systemic sclerosis that may alter the blood pattern of these compounds. This study aimed to evaluate changes in plasma concentrations of amino acid-related metabolites in systemic sclerosis in a search for potential biomarkers and mechanisms of the disease. Methods: Plasma samples from 42 patients diagnosed with systemic sclerosis (SSc) according to the 2013 American College of Rheumatology and European League Against Rheumatism ACR/EULAR classification criteria were compared to 27 matched healthy controls. Liquid chromatography/mass spectrometry was applied for the analysis of 36 amino acid-related metabolites. Results: The analysis of plasma AA metabolite patterns revealed the number of changes including an increase (20%) in concentrations of NO synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) in SSc vs. healthy subjects. Furthermore, SSc patients had higher glutamine, proline, betaine, 1-methylhistidine, and methylnicotinamide levels, while the concentration of tryptophan was lower. The specific metabolic pattern was identified for several aspects of disease presentation. Most interestingly NOS inhibitor L-NAME was elevated in patients with diffuse systemic sclerosis or telangiectasia. Conclusions: These results provide further evidence for the involvement of endothelium-dependent pathways in the mechanisms and presentation of SSc. Endothelial dysfunction biomarkers may be useful in the assessment of presentation and prognosis in SSc.

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Survival and organ involvement in patients with limited cutaneous systemic sclerosis and anti-topoisomerase-I antibodies: determined by skin subtype or auto-antibody subtype? A long-term follow-up study

Abstract: LcSSc ATA-positive patients differ from lcSSc ATA-negative patients and dcSSc ATA-positive patients concerning survival and organ involvement. LcSSc patients who are ATA-positive are more likely to develop dcSSc than lcSSc patients who are ATA negative.

Cited by 36 publications

References 25 publications

Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis

Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis

Classical Disease-Specific Autoantibodies in Systemic Sclerosis: Clinical Features, Gene Susceptibility, and Disease Stratification

Metabolic Pattern of Systemic Sclerosis: Association of Changes in Plasma Concentrations of Amino Acid-Related Compounds With Disease Presentation

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