| 1. |
- Mayes, Maureen D, et al.
(författare)
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Immunochip analysis identifies multiple susceptibility Loci for systemic sclerosis.
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 94:1, s. 47-61
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Tidskriftsartikel (refereegranskat)abstract
- In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.
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| 2. |
- Morrisroe, Kathleen, et al.
(författare)
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Determinants of health-related quality of life in a multinational systemic sclerosis inception cohort
- 2018
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Ingår i: Clinical and Experimental Rheumatology. - 0392-856X. ; 36:4, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate health-related quality of life (HRQoL) and its determinants in a systemic sclerosis (SSc) multinational inception cohort. We performed a meta-analysis of data from individual countries, and compared the meta-analysis to individual country results by pooling data from each of the countries.METHODS: SSc patients within 2 years of disease onset were recruited from 5 countries participating in the International Systemic Sclerosis Inception Cohort (INSYNC). Data from each country's database were exported for analysis using a harmonised platform. HRQoL was assessed using the Medical Outcomes Short Form-36 (SF-36). Multivariate linear regression assessed associations between HRQoL and predictors in cohorts separately and meta-analyzed to generate pooled estimates. The analyses were repeated using individual patient data.RESULTS: Of the 637 SSc patients recruited, the majority was female (80.2%-83.3%), aged between 52.4-56.7 years with limited cutaneous disease subtype (48.6%-66.7%). HRQoL scores were lower for SSc patients than the general population (SF-36 physical component summary (PCS) score (36.4-39.6), mental component summary (MCS) score (41.0-46.4)). Determinants of SF-36 PCS by meta-analysis included increasing age (β=-0.1, 95%CI -0.2, -0.01), diffuse cutaneous disease subtype (β=-8.4, 95%CI -10.6, -6.3), and pulmonary arterial hypertension (β=-10.9, 95%CI -16.6, -5.3). Increasing age (β=0.09, 95%CI 0.0, 0.18) was the only variable associated with SF-36 MCS. Analyses using individual patient data revealed similar results to those of the meta-analysis of cohort data.CONCLUSIONS: Our study provides estimates of HRQoL in a large inception SSc cohort and provides evidence that individual patient data analysis is valid in the INSYNC dataset.
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| 3. |
- Smith, Vanessa, et al.
(författare)
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Standardisation of nailfold capillaroscopy for the assessment of patients with Raynaud's phenomenon and systemic sclerosis
- 2020
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Ingår i: Autoimmunity Reviews. - : Elsevier BV. - 1568-9972. ; 19:3
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Forskningsöversikt (refereegranskat)abstract
- Capillaroscopy is a non-invasive and safe tool which allows the evaluation of the morphology of the microcirculation. Since its recent incorporation in the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for systemic sclerosis together with its assessed role to monitor disease progression, capillaroscopy became a ‘mainstream’ investigation for rheumatologists. Given its increasing use by a variety of physicians internationally both in daily practice to differentiate primary from secondary Raynaud's phenomenon, as well as in research context to predict disease progression and monitor treatment effects, standardisation in capillaroscopic image acquisition and analysis seems paramount. To step forward to this need, experts in the field of capillaroscopy/microcirculation provide in this very consensus paper their view on image acquisition and analysis, different capillaroscopic techniques, normal and abnormal capillaroscopic characteristics and their meaning, scoring systems and reliability of image acquisition and interpretation.
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