Very early and early systemic sclerosis in the Spanish scleroderma Registry (RESCLE) cohort

Trapiella-Martínez, Luis; Díaz-López, J. B.; Caminal-Montero, Luis; Tolosa-Vilella, Carles; Guillén‐Del‐Castillo, Alfredo; Colunga-Argüelles, Dolores; Rubio‐Rivas, Manuel; Iniesta-Arandia, Nerea; Castillo-Palma, María Jesús; Sáez‐Comet, Luis; Egurbide-Arberas, María Victoria; Ortego-Centeno, Norbérto; Freire, Mayka; Vargas‐Hitos, José Antonio; Ríos-Blanco, Juan José; Todolí-Parra, José Antonio; Rodríguez-Carballeira, Mónica; Marín-Ballvé, Adela; Chamorro, Antonio-Javier; Pla-Salas, Xavier; Madroñero-Vuelta, Ana Belén; Ruiz-Muñóz, Manuel; Fonollosa-Plà, Vicent; Simeón-Aznar, Carmen Pilar

doi:10.1016/j.autrev.2017.05.013

Cited by 17 publications

(10 citation statements)

References 48 publications

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“…The correct identification of patients with definite peripheral microvascular disturbances is prominent in order to define which ones deserve to be further investigated with a diagnostic work-up including auto-antibodies profile and nail fold capillaroscopy. Capillaroscopy is currently one of the most informative techniques for the diagnosis of RP and has been recommended in adults and in children because presence of specific abnormalities in nail fold capillaries is associated with a higher risk of development of a connective tissue disease, such as SSc and SLE [13, 14, 32–35]. In adults capillaroscopy showed high sensitivity and specificity in diagnosis of scleroderma-spectrum disorders, nevertheless it is still an operator-dependent technique so, in order to overcome the potential heterogeneity of images interpretation, continuous EUSTAR/EULAR effort is done to standardize the modality of assessment [36, 37].…”

Section: Discussionmentioning

confidence: 99%

Infrared thermography in children: a reliable tool for differential diagnosis of peripheral microvascular dysfunction and Raynaud’s phenomenon?

et al. 2019

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Background Infrared Thermography (IRT) has been used for over 30 years in the assessment of Raynaud Phenomenon (RP) and other peripheral microvascular dysfunctions in adults but, to date, very little experience is available on its use in children for this purpose. The first aim of the study was to assess reproducibility of thermographic examination after cold exposure by comparing inter-observer agreement in thermal imaging interpretation. The secondary aim was to evaluate whether IRT is reliable to diagnose and differentiate peripheral circulation disturbances in children. Methods Children with clinical diagnosis of primary Raynaud’s phenomenon (PRP), secondary RP (SRP), acrocyanosis (AC) and age-matched controls underwent sequential measurements of skin temperature at distal interphalangeal (DIP) and metacarpophalangeal (MCP) joints with IRT at baseline and for 10 min after cold challenge test. Intraclass correlation coefficient (ICC) was calculated for inter-rater reliability in IRT interpretation, then temperature variations at MCP and DIP joints and the distal-dorsal difference (DDD) were analysed. Results Fourteen PRP, 16 SRP, 14 AC and 15 controls entered the study. ICC showed excellent agreement (> 0.93) for DIPs and MCPs in 192 measures for each subject. Patients with PRP, SRP and acrocyanosis showed significantly slower recovery at MCPs (p < 0.05) and at DIPs (p < 0.001) than controls. At baseline, higher temperature at DIPs and lower at MCPs was observed in PRP compared with SRP with significantly lower DDD (p < 0.001). Differently from AC, both PRP and SRP showed gain of temperature at DIPs and less at MCPs after cold challenge. PRP but not SRP patients returned to DIPs basal temperature by the end of re-warming time. Analysis of DDD confirmed that controls and PRP, SRP and AC patients significantly differed in fingers recovery pattern (p < 0.05). Conclusion IRT appears reliable and reproducible in identifying children with peripheral microvascular disturbances. Our results show that IRT examination pointed out that PRP, SRP and AC patients present significant differences in basal extremities temperature and in re-warming pattern after cold challenge therefore IRT can be suggested as an objective tool for diagnosis and monitoring of disease.

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Section: Discussionmentioning

confidence: 99%

Infrared thermography in children: a reliable tool for differential diagnosis of peripheral microvascular dysfunction and Raynaud’s phenomenon?

et al. 2019

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“…Patients with SSc who fulfilled the 2013 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) criteria or the modified criteria proposed by LeRoy and Medsger in 1988 were included [32,33]. Four clinical subsets were considered: diffuse SSc, limited SSc, sine SSc, and early SSc (patients who met the criteria for very early disease and also presented incipient visceral involvement or other manifestations (digital ulcers (DU) or pitting scars, telangiectasia, calcinosis, or arthritis)) [4]. Characteristics of patient cohort are summarized in Additional file 1: Table S1. CD4+ T lymphocyte population was isolated from whole blood by fluorescence-activated cell sorting performed at the Unitat de Biologia (Campus de Bellvitge), Centres Científics i Tecnològics, Universitat de Barcelona (Spain).…”

Section: Patient Cohort and Cd4+ T Cell Isolationmentioning

confidence: 99%

“…SSc patients can be broadly categorized into three groups based on the extent of skin involvement: those with restricted involvement affecting the limbs distal to the elbows or knees with or without face and neck involvement are classified as limited cutaneous SSc (lcSSc) or those with proximal involvement affecting above the elbows and knees are classified as diffuse cutaneous SSc (dcSSc) and sine scleroderma with Raynaud's phenomenon, visceral involvement, and autoantibodies but no skin involvement [2]. A proposed classification by the Royal Free Hospital in 1996, currently used by Spanish Scleroderma Registry (RESCLE), included early (eSSc) and very early scleroderma [3,4]. The pathogenesis of SSc is not well-understood, in which disease onset and development appear to be multistep and multifactorial processes involving both genetic and environmental factors [5,6].…”

Section: Introductionmentioning

confidence: 99%

Epigenomics and transcriptomics of systemic sclerosis CD4+ T cells reveal long-range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci

Ortiz-Fernández

Andrés-León

et al. 2020

Genome Med

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Background Systemic sclerosis (SSc) is a genetically complex autoimmune disease mediated by the interplay between genetic and epigenetic factors in a multitude of immune cells, with CD4+ T lymphocytes as one of the principle drivers of pathogenesis. Methods DNA samples exacted from CD4+ T cells of 48 SSc patients and 16 healthy controls were hybridized on MethylationEPIC BeadChip array. In parallel, gene expression was interrogated by hybridizing total RNA on Clariom™ S array. Downstream bioinformatics analyses were performed to identify correlating differentially methylated CpG positions (DMPs) and differentially expressed genes (DEGs), which were then confirmed utilizing previously published promoter capture Hi-C (PCHi-C) data. Results We identified 9112 and 3929 DMPs and DEGs, respectively. These DMPs and DEGs are enriched in functional categories related to inflammation and T cell biology. Furthermore, correlation analysis identified 17,500 possible DMP-DEG interaction pairs within a window of 5 Mb, and utilizing PCHi-C data, we observed that 212 CD4+ T cell-specific pairs of DMP-DEG also formed part of three-dimensional promoter-enhancer networks, potentially involving CTCF. Finally, combining PCHi-C data with SSc GWAS data, we identified four important SSc-associated susceptibility loci, TNIP1 (rs3792783), GSDMB (rs9303277), IL12RB1 (rs2305743), and CSK (rs1378942), that could potentially interact with DMP-DEG pairs cg17239269-ANXA6, cg19458020-CCR7, cg10808810-JUND, and cg11062629-ULK3, respectively. Conclusion Our study unveils a potential link between genetic, epigenetic, and transcriptional deregulation in CD4+ T cells of SSc patients, providing a novel integrated view of molecular components driving SSc pathogenesis.

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“…for the generation and secretion of fibrotic and inflammatory cytokines, and play crucial roles in the pathogenesis of SSc. 19,20 In the present study, we identified mTOR signaling as an important KEGG pathway regarding the Res-targeted genes, and many prior studies have demonstrated that mTOR is an important factor in SSc. 21,22 Previous literature have also shown the mTOR signaling which may be regulated by the SIRT1 expression.…”

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confidence: 72%

<p>Resveratrol Ameliorates Systemic Sclerosis via Suppression of Fibrosis and Inflammation Through Activation of SIRT1/mTOR Signaling</p>

Yao¹,

Wu²,

Xu³

et al. 2020

DDDT

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Purpose Resveratrol (Res) is a natural polyphenolic compound found in several plants and reported as a promising biological molecule with effective anti-fibrosis and anti-inflammatory activities. However, the underlying mechanism of Res on systemic sclerosis (SSc) remains unclear. In the study, we identified the key cellular signaling pathways involved in the Res regulatory process on SSc. Methods Res-targeted genes interaction network was constructed using the STITCH database, and the shared Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in both SSc and Res-targeted genes were then identified. The top five enriched KEGG pathways were visualized by GOplot. KEGG pathways associated with Res-targeted genes were established by Pathway Builder Tool 2.0. Quantitative real-time PCR (qRT-PCR) was used to assess the expression of sirtuin 1 (SIRT1), mammalian targeted of rapamycin (mTOR), and cytokines. Results Enrichment analysis of Res-targeted genes showed 79 associated pathways, 27 of which were also involved in SSc. Particularly, SIRT1/mTOR signaling was found as one of the crucial regulatory pathways. In vitro results suggested that SIRT1-mediated mTOR degradation ameliorated bleomycin (BLM)-induced fibrosis and inflammation. Res was capable of elevating the SIRT1 level in fibroblasts and partially reversing mTOR-dependent induction of fibrosis and inflammation. Conclusion These results indicated that Res is a feasible and effective choice for SSc and therapeutic target of mTOR could be a potential alternative for treatment of SSc.

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Very early and early systemic sclerosis in the Spanish scleroderma Registry (RESCLE) cohort

Cited by 17 publications

References 48 publications

Infrared thermography in children: a reliable tool for differential diagnosis of peripheral microvascular dysfunction and Raynaud’s phenomenon?

Infrared thermography in children: a reliable tool for differential diagnosis of peripheral microvascular dysfunction and Raynaud’s phenomenon?

Epigenomics and transcriptomics of systemic sclerosis CD4+ T cells reveal long-range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci

<p>Resveratrol Ameliorates Systemic Sclerosis via Suppression of Fibrosis and Inflammation Through Activation of SIRT1/mTOR Signaling</p>

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