Autoantibodies in the disease criteria for systemic sclerosis: The need for specification for optimal application

Damoiseaux, Jan; Smeets, Ruben; Bonroy, Carolien

doi:10.1016/j.jtauto.2022.100141

Cited by 10 publications

(10 citation statements)

References 29 publications

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“…In fact, while extent of skin thickening and SSc-specific autoantibodies are recognized to have important prognostic implications and are included in the classification criteria for this disease, most classification criteria represent vasculopathy manifestations, highlighting the importance of vascular assessment [3]. Although classification criteria are not designed for diagnostic purposes, in the absence of diagnostic criteria, the classification criteria are often used to by clinicians during the work-up of patients with concern for SSc as the diagnosis [4]. Assessment of vascular involvement is similarly important for SSc patient management, as the disease is a progressive self-amplifying process, which first involves the microvascular/endothelial damage, followed by autoimmune response and inflammation, and finally fibrosis [1].…”

Section: Introductionmentioning

confidence: 99%

Imaging techniques for assessment of vascular involvement in systemic sclerosis

Frech

2022

Current Opinion in Rheumatology

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Purpose of reviewVascular assessment in systemic sclerosis (SSc) is included in classification criteria for this disease, thus routinely used in the evaluation of patients in which this diagnosis is being considered. In this review, imaging techniques for assessment of vascular involvement in SSc hands and skin are discussed. Recent findingsLongitudinal use of imaging techniques has important implications for understanding the progressive vasculopathy and fibrotic transition in SSc. Nailfold and oral capillaroscopy as well as laser speckle contrast analysis are established techniques for vascular functional assessment, but longitudinal use is challenged by equipment costs and clinical time constraints. Ultrasound techniques are well described but require technical training. Advances in mobile infrared thermography and optical coherence tomography could potentially provide a point-of-care, quantitative outcome measure in clinical trials and practice.

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Section: Introductionmentioning

confidence: 99%

Imaging techniques for assessment of vascular involvement in systemic sclerosis

Frech

2022

Current Opinion in Rheumatology

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“… 45 Herein, however, apart from autoantibodies against Ro52/SSA, which was significantly more common in pSS and SLE than in SSc, only autoantibodies against CENP-A (SLE both cohorts and pSS), CENP-B (pSS) and Ku (SLE replication cohort) were positive in ≥5% indicating that the cut-offs applied by the manufacturer were mostly acceptable. 46 However, surprisingly, many samples from the HBD and SLE discovery cohorts showed positivity for the rare specificities Th/To and NOR90, respectively, and only few of these could be verified with BlueDot and EliA. This does raise the question of not only the cut-off, but also of the source and selection of antigens included in the Euroimmun assay.…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies associated with systemic sclerosis in three autoimmune diseases imprinted by type I interferon gene dysregulation: a comparison across SLE, primary Sjögren’s syndrome and systemic sclerosis

et al. 2022

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ObjectiveSLE, primary Sjögren’s syndrome (pSS) and systemic sclerosis (SSc) are heterogeneous autoimmune diseases with a dysregulated type I interferon (IFN) system. The diseases often show overlapping clinical manifestations, which may result in diagnostic challenges. We asked to which extent SSc-associated autoantibodies are present in SLE and pSS, and whether these link to serum IFN-α, clinical phenotypes and sex. Samples with clinical data from patients with SSc and healthy blood donors (HBDs) served as controls. Finally, the diagnostic performance of SSc-associated autoantibodies was evaluated.MethodsSamples from well-characterised subjects with SLE (n=510), pSS (n=116), SSc (n=57) and HBDs (n=236) were analysed using a commercially available immunoassay (EuroLine Systemic Sclerosis Profile (IgG)). IFN-α was quantified by ELISA. Self-reported data on Raynaud’s phenomenon (RP) were available.ResultsWith exceptions for anti-Ro52/SSA and anti-Th/To, SSc-associated autoantibodies were more frequent in SSc than in SLE, pSS and HBDs regardless of sex. IFN-α levels correlated with the number of positive SSc-associated autoantibodies (r=0.29, p<0.0001) and associated with Ro52/SSA positivity (p<0.0001). By using data from SLE, SSc and HBDs, RP was significantly associated with topoisomerase I, centromere protein (CENP)-B, RNA polymerase III 11 kDa, RNA polymerase III 155 kDa and PM-Scl100 whereas Ro52/SSA associated inversely with RP. In SLE, CENP-A was associated with immunological disorder, CENP-B with serositis and Ku with lupus nephritis. By combining analysis of ANA (immunofluorescence) with SSc-associated autoantibodies, the diagnostic sensitivity reached 98% and the specificity 33%.ConclusionsThe 13 specificities included in the EuroLine immunoassay are commonly detected in SSc, but they are also frequent among individuals with other diseases imprinted by type I IFNs. These findings are valuable when interpreting serological data on patients with suspected SSc, especially as patients may present with disease manifestations overlapping different rheumatological diseases. In SLE, we observed associations between manifestations and SSc-associated autoantibodies which have not previously been reported.

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“…However, additional techniques, such as enzyme-linked immunosorbent assay (ELISA), immunodiffusion and immunoprecipitation, are used to identify specific SSc autoantibodies ( 13 , 39 , 40 ). Although, these immuno-assays may differ in terms of test characteristics and validation of results is crucial ( 41 , 42 ).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive autoantibody profiles in systemic sclerosis: Clinical cluster analysis

Höppner

Tabeling²,

Casteleyn³

et al. 2023

Front. Immunol.

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BackgroundSystemic sclerosis (SSc) belongs to the group of connective tissue diseases and is associated with the occurrence of disease-specific autoantibodies. Although it is still controversial whether these antibodies contribute to pathogenesis, there are new insights into the development of these specific antibodies and their possible pathophysiological properties. Interestingly, they are associated with specific clinical manifestations, but for some rarer antibodies this association is not fully clarified. The aim of this study is a comprehensive analysis of the serum autoantibody status in patients with SSc followed by correlation analyses of autoantibodies with the clinical course of the disease.MethodsSerum from SSc patients was analyzed using a line blot (EUROLINE, EUROIMMUN AG) for SSc-related autoantibodies. Autoantibodies to centromere, Topo-1, antimitochondrial antibodies (AMA) M2 subunit, angiotensin II type 1 receptors (AT1R) and endothelin-1 type-A-receptors (ETAR) were also determined by ELISA. We formed immunological clusters and used principal components analysis (PCA) to assign specific clinical characteristics to these clusters.ResultsA total of 372 SSc patients were included. 95.3% of the patients were antinuclear antibody positive and in 333 patients at least one SSc specific antibody could be detected. Four immunological clusters could be found by PCA. Centromere, Topo-1 and RP3 all formed own clusters, which are associated with distinct clinical phenotypes. We found that patients with an inverted phenotype, such as limited cutaneous SSc patients within the Topo-1 cluster show an increased risk for interstital lung disease compared to ACA positive patients. Anti-AT1R and anti-ETAR autoantibodies were measured in 176 SSc patients; no association with SSc disease manifestation was found. SSc patients with AMA-M2 antibodies showed an increased risk of cardiovascular events.ConclusionIn our in large cluster analysis, which included an extended autoantibody profile, we were able to show that serologic status of SSc patients provides important clues to disease manifestation, co-morbidities and complications. Line blot was a reliable technique to detect autoantibodies in SSc and detected rarer autoantibodies in 42% of our patients.

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Autoantibodies in the disease criteria for systemic sclerosis: The need for specification for optimal application

Cited by 10 publications

References 29 publications

Imaging techniques for assessment of vascular involvement in systemic sclerosis

Imaging techniques for assessment of vascular involvement in systemic sclerosis

Autoantibodies associated with systemic sclerosis in three autoimmune diseases imprinted by type I interferon gene dysregulation: a comparison across SLE, primary Sjögren’s syndrome and systemic sclerosis

Comprehensive autoantibody profiles in systemic sclerosis: Clinical cluster analysis

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