Evaluation of a new multi-parallel line immunoassay for systemic sclerosis-associated antibodies in an Asian population

Low, Albert; Wong, Stephen; Thumboo, Julian; Ng, S. C.; Lim, Jia Yuen; Ng, Xinyi; Earnest, Arul; Fong, Kok Yong

doi:10.1093/rheumatology/kes055

Cited by 23 publications

(21 citation statements)

References 18 publications

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“…The remainder of patients who had a clinical association with diffuse SSc were captured in cluster topo I (18%). Topo I frequencies were consistent with the frequencies reported in other international registries of similar ethnicity but varying geographic locations, and it should be noted that the frequencies of this autoantibody vary with ethnicity . Significant clinical associations in this cohort include high MRSS, ILD, joint contractures, and digital ulcers.…”

Section: Discussionsupporting

confidence: 87%

“…Prevalence rates for RNAP III vary according to ethnicity and geographic location. The frequency of RNAP III in this cohort lies somewhere between the rates identified in other international cohorts . Cluster RNAP III strong patients had the highest MRSS, while cluster RNAP III weak patients had the second highest MRSS, equaling that for cluster topo I (Supplementary Figure 4, available on the Arthritis & Rheumatology web site at http://onlinelibrary.wiley.com/doi/10.1002/art.39316/abstract).…”

Section: Discussionmentioning

confidence: 49%

“…All scores were then used in the principal components analysis. Separate studies have found good correlation between the signal intensity in the immunoblot assay and autoantibody titers/concentrations measured in alternative assays .…”

Section: Methodsmentioning

confidence: 99%

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Interpretation of an Extended Autoantibody Profile in a Well‐Characterized Australian Systemic Sclerosis (Scleroderma) Cohort Using Principal Components Analysis

Patterson

Roberts‐Thomson

Lester

et al. 2015

Arthritis & Rheumatology

107

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Objective. To determine the relationships between systemic sclerosis (SSc)-related autoantibodies, as well as their clinical associations, in a well-characterized Australian patient cohort.Methods. Serum from 505 Australian SSc patients were analyzed with a commercial line immunoassay (EuroLine; Euroimmun) for autoantibodies to centromere proteins CENP-A and CENP-B, RNA polymerase III (RNAP III; epitopes 11 and 155), the 90-kd nucleolar protein NOR-90, fibrillarin, Th/To, PM/Scl-75, PM/Scl-100, Ku, topoisomerase I (topo I), tripartite motif-containing protein 21/Ro 52, and platelet-derived growth factor receptor. Patient subgroups were identified by hierarchical clustering of the first 2 dimensions of a principal components analysis of quantitative autoantibody scores. Results were compared with detailed clinical data.Results. A total of 449 of the 505 patients were positive for at least 1 autoantibody by immunoblotting. Heatmap visualization of autoantibody scores, along with principal components analysis clustering, demonstrated strong, mutually exclusive relationships between CENP, RNAP III, and topo I. Five patient clusters were identified: CENP, RNAP III strong, RNAP III weak, topo I, and other. Clinical features associated with CENP, RNAP III, and topo I were consistent with previously published reports concerning limited cutaneous and diffuse cutaneous SSc. A novel finding was the statistical separation of RNAP III into 2 clusters. Patients in the RNAP III strong cluster had an increased risk of gastric antral vascular ectasia, but a lower risk of esophageal dysmotility. Patients in the other cluster were more likely to be male and to have a history of smoking and a history of malignancy, but were less likely to have telangiectasia, Raynaud's phenomenon, and joint contractures.Conclusion. Five major autoantibody clusters with specific clinical and serologic associations were identified in Australian SSc patients. Subclassification and disease stratification using autoantibodies may have clinical utility, particularly in early disease.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 49%

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Interpretation of an Extended Autoantibody Profile in a Well‐Characterized Australian Systemic Sclerosis (Scleroderma) Cohort Using Principal Components Analysis

Patterson

Roberts‐Thomson

Lester

et al. 2015

Arthritis & Rheumatology

107

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“…Our patients with DcSSc were also more likely to have proximal myopathy and raised muscle enzymes. of Chinese SSc patients in a Canadian cohort and a Singapore study validating a new line immunoassay for the detection of SSc-associated autoantibodies 4,5 . The clinical significance of the above findings will need to be further investigated.…”

Section: Disease Characteristicsmentioning

confidence: 99%

Disease Characteristics of the Singapore Systemic Sclerosis Cohort

Ling

Gee

Giap

et al. 2013

Proceedings of Singapore Healthcare

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Introduction: Systemic sclerosis (SSc) has one of the worst prognoses among autoimmune diseases. Multi-ethnic Western cohorts have shown ethnic differences in disease characteristics. Due to a paucity of data in Asia, we aimed to describe the disease characteristics and autoantibody profile of Asian SSc patients. Methods: The Singapore SSc database consists of prevalent and incident cases from four institutions. Data were recorded annually according to a standardised protocol. Cumulative disease characteristics were analysed using descriptive statistics. Results: From 2008 to 2012, 200 patients (85.5% females; Chinese 78%, Malays 10.5%, Indians 6%) diagnosed at a mean age of 46 years, fulfilled the American College of Rheumatology (ACR) (88.0%) or the Very Early Diagnosis of SSc (VEDOSS) (12%) criteria. SSc subtypes include limited cutaneous SSc (LcSSc) (32%) or diffuse cutaneous SSc (DcSSc) (37.6%), SSc-overlap syndromes (27.4%) and sine scleroderma (3%). Predominant disease manifestations were Raynaud's phenomenon (n=161, 80.5%), gastrointestinal (GI) (n=125, 62.5%), joint pain (n=116, 58%) and interstitial lung disease (ILD) (n=99, 51.8%). Pulmonary arterial hypertension (PAH) by echocardiography was present in 23.2% (39/168) of patients (mean systolic pulmonary arterial pressure 55.0+19.7mmHg). Renal crisis was rare (n=4, 2%). Anti-nuclear antibodies (ANA) tested positive in 78.7% (155/197), with anti-Scl-70 (69/197, 35.0%), anti-ribonucleoprotein (RNP) (56/192, 29.2%) and anti-Ro60 (40/193, 20.7%) most frequently detected. Anti-centromere antibodies were infrequent (23/190, 12.1%). Treatment included corticosteroids (80.7%), for peripheral vasculopathy (61.4%), GI (68%), PAH (11.2%) and immunosuppression (62.9%). Conclusion: Compared to Caucasian patients, our predominantly Chinese Asian SSc patients were diagnosed at an earlier age, with more severe PAH, less frequent Raynaud's phenomenon, an autoantibody profile characterised by anti-Scl70, anti-RNP and anti-Ro60, infrequently anti-centromere and more patients had DcSSc.

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“…Donor CD4 + T cells may contribute to the expansion of plasmablasts and LLPCs, as is the case with the WT1-peptide immunization model. 12 The clinical findings that anti-RP155 Abs have been observed in systemic sclerosis but not in SLE 13 also support the hypothesis that the auto-Abs were derived from donor cells and not patient cells. However, the presence of auto-Ab against RNP70 could not be explained by this hypothesis.…”

mentioning

confidence: 59%

Changes in the autoantibody pattern during allogeneic stem-cell transplantation for acute myeloid leukemia complicated by systemic lupus erythematosus

Arita

Murakami

Wada

et al. 2016

Bone Marrow Transplant

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Evaluation of a new multi-parallel line immunoassay for systemic sclerosis-associated antibodies in an Asian population

Abstract: The SSc-LIA has good agreement with conventional techniques for selected antibodies and has good diagnostic utility.

Cited by 23 publications

References 18 publications

Interpretation of an Extended Autoantibody Profile in a Well‐Characterized Australian Systemic Sclerosis (Scleroderma) Cohort Using Principal Components Analysis

Interpretation of an Extended Autoantibody Profile in a Well‐Characterized Australian Systemic Sclerosis (Scleroderma) Cohort Using Principal Components Analysis

Disease Characteristics of the Singapore Systemic Sclerosis Cohort

Changes in the autoantibody pattern during allogeneic stem-cell transplantation for acute myeloid leukemia complicated by systemic lupus erythematosus

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