Additional file 2: Table S2. of The HLA-B*35 allele modulates ER stress, inflammation and proliferation in PBMCs from Limited Cutaneous Systemic Sclerosis patients

List of Gene Sets: 64 pathways sorted by LS permutation p-value. (XLS 152 kb

Additional file 4: Figure S2. of The HLA-B*35 allele modulates ER stress, inflammation and proliferation in PBMCs from Limited Cutaneous Systemic Sclerosis patients

HLA-B*35 is associated with low levels of selected cyclin inhibitors and pro-apoptotic genes in lcSSc PBMCs. PBMCs were isolated from HC (n = 49), lcSSc (n = 81, NoPAH n = 43, and PAH n = 38) and grouped according to the presence of the HLA-B*35 allele: HC B35+ (n = 9), HC B35- (n = 40); lcSSc NoPAH B35+ (n = 14), lcSSc NoPAH B35- (n = 29), lcSSc PAH B35+ (n = 12) and lcSSc PAH B35- (n = 26). mRNA levels of p21, p57 (a), Bax, Gadd45 (b), and FYN, ATM (c) were measured by qPCR. Expression of the housekeeping genes β-actin, GADPH and 18S served as internal controls in each assay performed. (TIF 1.63 mb

Additional file 1: Table S1. of The HLA-B*35 allele modulates ER stress, inflammation and proliferation in PBMCs from Limited Cutaneous Systemic Sclerosis patients

Clinical and hemodynamic data of study subjects. PAP = pulmonary artery pressure. PCWP = pulmonary capillary wedge pressure. CO/CI = Cardiac output (L/min)/ cardiac index (L/min/m2). PVR = pulmonary vascular resistance. ILD = interstitial lung disease. FVC (%) = estimated forced vital capacity. DLCO = carbon monoxide diffusing capacity. SPAP = estimated systolic pulmonary artery pressure by echocardiogram. ILD was defined as present (Y = yes) or absent (N = no) based on high-resolution computed tomography assessment of the lungs. (XLS 73.5 kb

DataSheet_2_Reactome pathway analysis from whole-blood transcriptome reveals unique characteristics of systemic sclerosis patients at the preclinical stage.docx

ObjectiveThis study aims to characterize differential expressed pathways (DEP) in subjects with preclinical systemic sclerosis (PreSSc) characterized uniquely by Raynaud phenomenon, specific autoantibodies, and/or capillaroscopy positive for scleroderma pattern.MethodsWhole-blood samples from 33 PreSSc with clinical prospective data (baseline and after 4 years of follow-up) and 16 matched healthy controls (HC) were analyzed for global gene expression transcriptome analysis via RNA sequencing. Functional Analysis of Individual Microarray Expression method annotated Reactome individualized pathways. ANOVA analysis identified DEP whose predictive capability were tested in logistic regression models after extensive internal validation.ResultsAt 4 years, 42.4% subjects progressed (evolving PreSSc), while the others kept stable PreSSc clinical features (stable PreSSc). At baseline, out of 831 pathways, 541 DEP were significant at a false discovery rate ConclusionPreSSc had distinguished Reactome pathway signatures compared to HC. Progression to definite SSc was characterized by a shift in biological fingertips. Calcium-related events promoting endothelial damage and vasculopathy may be relevant to disease progression.</p

DataSheet_1_Reactome pathway analysis from whole-blood transcriptome reveals unique characteristics of systemic sclerosis patients at the preclinical stage.xlsx

ObjectiveThis study aims to characterize differential expressed pathways (DEP) in subjects with preclinical systemic sclerosis (PreSSc) characterized uniquely by Raynaud phenomenon, specific autoantibodies, and/or capillaroscopy positive for scleroderma pattern.MethodsWhole-blood samples from 33 PreSSc with clinical prospective data (baseline and after 4 years of follow-up) and 16 matched healthy controls (HC) were analyzed for global gene expression transcriptome analysis via RNA sequencing. Functional Analysis of Individual Microarray Expression method annotated Reactome individualized pathways. ANOVA analysis identified DEP whose predictive capability were tested in logistic regression models after extensive internal validation.ResultsAt 4 years, 42.4% subjects progressed (evolving PreSSc), while the others kept stable PreSSc clinical features (stable PreSSc). At baseline, out of 831 pathways, 541 DEP were significant at a false discovery rate ConclusionPreSSc had distinguished Reactome pathway signatures compared to HC. Progression to definite SSc was characterized by a shift in biological fingertips. Calcium-related events promoting endothelial damage and vasculopathy may be relevant to disease progression.</p

Image_1_Reactome pathway analysis from whole-blood transcriptome reveals unique characteristics of systemic sclerosis patients at the preclinical stage.jpeg

ObjectiveThis study aims to characterize differential expressed pathways (DEP) in subjects with preclinical systemic sclerosis (PreSSc) characterized uniquely by Raynaud phenomenon, specific autoantibodies, and/or capillaroscopy positive for scleroderma pattern.MethodsWhole-blood samples from 33 PreSSc with clinical prospective data (baseline and after 4 years of follow-up) and 16 matched healthy controls (HC) were analyzed for global gene expression transcriptome analysis via RNA sequencing. Functional Analysis of Individual Microarray Expression method annotated Reactome individualized pathways. ANOVA analysis identified DEP whose predictive capability were tested in logistic regression models after extensive internal validation.ResultsAt 4 years, 42.4% subjects progressed (evolving PreSSc), while the others kept stable PreSSc clinical features (stable PreSSc). At baseline, out of 831 pathways, 541 DEP were significant at a false discovery rate ConclusionPreSSc had distinguished Reactome pathway signatures compared to HC. Progression to definite SSc was characterized by a shift in biological fingertips. Calcium-related events promoting endothelial damage and vasculopathy may be relevant to disease progression.</p

Table_2_Reactome pathway analysis from whole-blood transcriptome reveals unique characteristics of systemic sclerosis patients at the preclinical stage.docx

ObjectiveThis study aims to characterize differential expressed pathways (DEP) in subjects with preclinical systemic sclerosis (PreSSc) characterized uniquely by Raynaud phenomenon, specific autoantibodies, and/or capillaroscopy positive for scleroderma pattern.MethodsWhole-blood samples from 33 PreSSc with clinical prospective data (baseline and after 4 years of follow-up) and 16 matched healthy controls (HC) were analyzed for global gene expression transcriptome analysis via RNA sequencing. Functional Analysis of Individual Microarray Expression method annotated Reactome individualized pathways. ANOVA analysis identified DEP whose predictive capability were tested in logistic regression models after extensive internal validation.ResultsAt 4 years, 42.4% subjects progressed (evolving PreSSc), while the others kept stable PreSSc clinical features (stable PreSSc). At baseline, out of 831 pathways, 541 DEP were significant at a false discovery rate ConclusionPreSSc had distinguished Reactome pathway signatures compared to HC. Progression to definite SSc was characterized by a shift in biological fingertips. Calcium-related events promoting endothelial damage and vasculopathy may be relevant to disease progression.</p

Association of ECG findings with low ejection fraction and elevated right ventricular systolic pressure on echocardiogram.

<p>Association of ECG findings with low ejection fraction and elevated right ventricular systolic pressure on echocardiogram.</p

Characteristics of patients with and without ECG abnormalities in the GENISOS Study Population.

<p>Characteristics of patients with and without ECG abnormalities in the GENISOS Study Population.</p

Frequencies of different ECG findings and their impact on mortality in the GENISOS cohort.

<p>Frequencies of different ECG findings and their impact on mortality in the GENISOS cohort.</p