Marker For Systemic Sclerosis Research Articles

Low-Frequency Magnetic Resonance Imaging Identifies Hand Joint Subclinical Inflammation in Systemic Sclerosis.

Objectives: The aim of this work was to determine hand joint inflammation in systemic sclerosis (SSc); patients with rheumatoid arthritis (RA) with hand joint involvement were used as controls. Our investigation also aimed at examining the relationship between these subclinical inflammatory changes in the hands, verified by low-frequency MRI, and clinical (especially cardiopulmonary) manifestations, disease activity, and functional capacity in patients with diffuse cutaneous (dcSSc) and limited cutaneous SSc (lcSSc). Methods: Out of 250 SSc patients, the selection included 82 patients with signs and symptoms of joint involvement, and 35 consecutive RA patients. These patients underwent clinical and laboratory investigations, and hand X-ray and MRI of the dominant hand. Synovitis/tenosynovitis, bone edema, and erosions were investigated, and the bone changes were quantified and scored using the RAMRIS method. HAQ index, modified Rodnan skin score, examination of internal organ involvement, and serological markers for SSc, as well as rheumatoid factor (RF) and cyclic citrullinated peptides antibodies (ACPA), were performed on all experimental group subjects. Results: MRI of the dominant hand showed a significantly higher number of cases with synovitis (78%) than the number of patients with clinically swollen joints (17.1%; p < 0.001); bone edema was found in 62 (75.6%) SSc patients. MRI also showed a higher number of erosions (52; 63.4%) compared to those (22; 27.5%) detected with X-ray (p < 0.001). The average values of the total MRI score of synovitis/edema and erosions in the wrist (p < 0.001) and MCP joints (p < 0.001) were statistically higher in RA than in SSc patients (p < 0.001). The probability of the MRI-detected inflammatory changes was considerably higher in SSc patients who had vascular complications (digital ulceration, OR = 4.68; 95% IP: 1.002–22.25; p < 0.05), in patients with more severe functional impairment (OR = 8.22; 95% IP: 1.74–38.89; p < 0.01), and in patients with active disease (OR = 3.132; 95% IP: 1.027–9.551; p < 0.05). In our investigation, patients with a limited form of the disease and with inflammatory changes on MR more often had higher functional impairment compared to the other group without MRI inflammation. Conclusions: Our data show that in SSc MRI can detect a significant subclinical joint inflammation. RAMRIS confirmed the high degree of joint inflammation in RA, but also revealed a great deal of joint inflammation in SSc. That inflammation is associated with systemic inflammation (disease activity), vascular complications, and more severe forms of the disease, as synovitis cannot be precisely diagnosed by the clinical examination of joints. These results suggest that a careful joint investigation is necessary in SSc, and that in symptomatic patients, MRI may identify joint inflammation. In clinical practice, this evidence might drive to an early targeted therapy, thus preventing joint erosions.

Serum markers of cardiac complications in a systemic sclerosis cohort

Primary cardiac involvement is one of the leading causes of mortality in systemic sclerosis (SSc), but little is known regarding circulating biomarkers for cardiac SSc. Here, we aimed to investigate potential associations between cardiac SSc and candidate serum markers. Serum samples from patients of the Oslo University SSc cohort and 100 healthy controls were screened against two custom-made candidate marker panels containing molecules deemed relevant for cardiopulmonary and/or fibrotic diseases. Left (LV) and right ventricular (RV) dysfunction was assessed by protocol echocardiography, performed within three years from serum sampling. Patients suspected of pulmonary hypertension underwent right heart catheterization. Vital status at study end was available for all patients. Descriptive analyses, logistic and Cox regressions were conducted to assess associations between cardiac SSc and candidate serum markers. The 371 patients presented an average age of 57.2 (± 13.9) years. Female sex (84%) and limited cutaneous SSc (73%) were predominant. Association between LV diastolic dysfunction and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (OR 0.41, 95% CI 0.21–0.78, p = 0.007) was identified. LV systolic dysfunction defined by global longitudinal strain was associated with angiopoietin 2 (ANGPT2) (OR 3.42, 95% CI 1.52–7.71, p = 0.003) and osteopontin (OPN) (OR 1.95, 95% CI 1.08–3.52, p = 0.026). RV systolic dysfunction, measured by tricuspid annular plane systolic excursion, was associated to markers of LV dysfunction (ANGPT2, OPN, and TRAIL) (OR 1.67, 95% CI 1.11–2.50, p = 0.014, OR 1.86, 95% CI 1.25–2.77, p = 0.002, OR 0.32, 95% CI 0.15–0.66, p = 0.002, respectively) and endostatin (OR 1.86, 95% CI 1.22–2.84, p = 0.004). In conclusion, ANGPT2, OPN and TRAIL seem to be circulating biomarkers associated with both LV and RV dysfunction in SSc.

Early changes of pulmonary arterial hemodynamics in patients with systemic sclerosis: flow pattern, WSS, and OSI analysis with 4D flow MRI.

To study the pulmonary artery (PA) hemodynamics in patients with systemic sclerosis (SSc) using 4D flow MRI (4D-flow). Twenty-three patients with SSc (M/F: 2/21, 57 ± 15years, 3 manifest PA hypertension (PAH) by right heart catheterization) and 10 control subjects (M/F: 1/9, 55 ± 17years) underwent 4D-flow for the in vivo measurement of 3D blood flow velocities in the PA. Data analysis included area-averaged flow quantification at the main PA, 3D wall shear stress (WSS), oscillatory shear index (OSI) calculation along the PA surface, and Reynolds number. The composite outcome of all-cause death and major adverse cardiac events was also investigated. The maximum PA flow at the systole did not differ, but the minimum flow at the diastole was significantly greater in patients with SSc compared with that in control subjects (7.7 ± 16.0ml/s vs. ‑13.0 ± 17.3ml/s, p < 0.01). The maximum WSS at the peak systole was significantly lower and OSI was significantly greater in patients with SSc compared with those in control subjects (maximum WSS: 1.04 ± 0.20Pa vs. 1.33 ± 0.34Pa, p < 0.01, OSI: 0.139 ± 0.031 vs. 0.101 ± 0.037, p < 0.01). The cumulative event-free rate for the composite event was significantly lower in patients with minimum flow in main PA ≤ 9.22ml/s (p = 0.012) and in patients with Reynolds number ≤ 2560 (p < 0.001). 4D-flow has the potential to detect changes of PA hemodynamics noninvasively and predict the outcome in patients with SSc at the stage before manifest PAH. • The WSS at the peak systolic phase was significantly lower (p < 0.05), whereas OSI was greater (p < 0.01) in patients with SSc without manifest PAH than in controls. • The hemodynamic change detected by 4D-flow may help patient management even at the stage before manifest PAH in SSc. • The minimum PA flow and Reynolds number by 4D-flow will serve as a predictive marker for SSc.

Clinical consequences of the presence of anti-RNA Pol III antibodies in systemic sclerosis.

IntroductionAnti-RNA polymerase III (a-RNA Pol III) antibodies are marker antibodies in patients with systemic sclerosis (SSc).AimTo assess the prevalence of a-RNA Pol III in patients with SSc and to identify the differences in the disease picture in SSc patients with and without a-RNA Pol III antibodies.Material and methodsThe study was performed in 126 SSc patients. The subtype of SSc, incidence of internal organ involvement, malignancy, death and serological profiles were determined in the entire group. The study groups were studied according to the presence of antibodies by applying the commercial test – EUROLINE SSc Profile. Due to the presence of a-RNA Pol III, patients were divided into two groups: the a-RNA Pol III (+) SSc group of 19 patients and the a-RNA Pol III (–) SSc group of 107 patients.ResultsA-RNA Pol III were present in 19/126 patients with SSc (15%), 13/19 (68.4%) patients had no other SSc marker antibodies. A-RNA Pol III were more common in patients with diffuse cutaneous SSc (p = 0.049). We showed a significant positive association between a-RNA Pol III and occurrence of malignancy (p = 0.007), scleroderma renal crisis (p = 0.001) and decreased DLCO (p = 0.007).ConclusionsAnti-a-RNA Pol III antibodies are common in patients with SSc, particularly with a diffuse subtype. In more than 50% of patients with a-RNA Pol III antibodies, they may be present as the sole marker of antibodies. In SSc, a-RNA Pol III antibodies are frequently associated with malignancy occurrence, kidney and lung involvement.

Macrophage migration inhibitory factor polymorphisms are a potential susceptibility marker in systemic sclerosis from southern Mexican population: association with MIF mRNA expression and cytokine profile.

Systemic sclerosis (SSc) is a complex autoimmune disease, characterized by microvascular lesions, autoimmunity, and fibrosis. It is suggested that MIF participates in the amplification of the proinflammatory process in SSc; moreover, the promoter polymorphisms - 794 CATT5-8 (rs5844572) and - 173G>C (rs755622) in the MIF gene have been associated with an increase in MIF serum levels in several autoimmune diseases. The aim of this study was to analyze the relationship of the - 794 CATT5-8 and - 173G>C MIF polymorphisms with mRNA expression, MIF serum levels, and the Th1/Th2/Th17 cytokine profile in SSc. A case-control study was carried out that included 50 patients with SSc and 100 control subjects (CS). Both polymorphisms were genotyped by PCR and PCR-RFLP. MIF levels were measured by ELISA kit. The cytokine profile and the MIF mRNA expression were quantified by BioPlex MagPix system and real-time PCR, respectively. An association between the - 794 CATT7 and - 173*C MIF alleles and the 7C haplotype with SSc susceptibility was found (p < 0.05). Also, the 7C haplotype was associated with increased MIF mRNA expression (p =0.03) in SSc. In addition, an increase of IL-1β and IL-6 serum levels in SSc patients was found as well as a positive correlation between MIF serum levels and Th1 and Th17 cytokine profiles. The MIF 7C haplotype is a susceptibility marker for SSc in the southern Mexican population and is associated with MIF mRNA expression. Moreover, there is a positive correlation between MIF serum levels and Th1 and Th17 inflammatory response in SSc.

Evaluation of Anti-Centromere Antibodies, Anti-SSA and Anti-SSB in Serum and Saliva of Patients with Systemic Sclerosis

Background: Systemic sclerosis (SSc) is a chronic autoimmune illness, which is consider by three main features: Sclerotic changes in the skin and internal organs, Vasculopathy of small blood vessels, Particular autoantibodies (1). The most important autoantibodies appeared significantly in SSc patients are anti-topoisomerase I autoantibody (Scl-70), anti-centromere autoantibody (ACA), and anti-RNA polymerase III autoantibody (RNAP3) (2). Anti-centromere antibodies (ACA) are infrequent in rheumatic conditions and in healthy persons but occur commonly in limited systemic sclerosis (CREST syndrome), and rarely appeared in the diffuse form of systemic sclerosis (3). Anti-Ro/SSA and antiLa/SSB, antibodies directed against Ro/La ribonucleoprotein complexes, can serve as a diagnostic hallmark of autoimmune disease specially Sjogren’s syndrome (4). Materials and methods: This study was carried out during the period from the middle of November 2015 until the end of November 2016 in Baghdad city. The sample of this study was divided into two groups : Forty systemic sclerosis patients: Those patients were treated at Rheumatology department in Baghdad teaching hospital in Baghdad city as well as Forty healthy control subjects, age matched with no signs and symptoms of any systemic diseases. Results: The serum anti-SSA in SSc patient was significant increased as well as the salivary anti-SSA in SSc patient was highly significantly increased than in the control subjects by using t-test. The present study found that there no statically difference in salivary ACA, anti-SSB and serum anti-SSB while serum ACA was significantly increased. Conclusions: autoantibodies play a role in pathogenesis of SSc patients represented by increased serum (ACA and anti-SSA) that it considered reliable indicator for SSc patients while unpredicted marker in saliva except anti-SSA. Anti-La/SSB is unreliable marker in both serum and saliva SSc patients. The presence of Anti-Ro/SSA antibodies in serum and saliva of SSc patient has been predictive marker for SSc overlapped Sjogren’s syndrome.

The fact not to ignore: Mean blood pressure is the main predictor of increased arterial stiffness in patients with systemic rheumatic diseases

PurposeWe aimed to evaluate the association between carotid-radial pulse wave velocity (PWV), augmentation index (AIx), and flow-mediated dilatation (FMD) of the brachial artery and factors potentially influencing them in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Material and methods316 patients diagnosed with RA (32%), SLE (20%), SSc (16%) and 156 controls (32%) were included in the study. Parameters of arterial stiffness AIx and PWV were obtained using applanation tonometry. FMD reflecting endothelial function was measured by ultrasound. ResultsAIx was increased in all three diseases (p<0.0001), but no differences were found between rheumatic diseases. In most of the RA cases PWV values were abnormal (on average by 0.52m/sec higher than in controls), while in SSc patients FMD values were diminished (p=0.006). Mean blood pressure (MBP) was the most consistent predictive factor in all three diseases, influencing both PWV and AIx, although patient age was also important in variation of AIx. The disease activity score (DAS28) was relevant only in RA patients. Furthermore, SLE disease activity index in SLE or Rodnan skin thickness score had no statistical significance in SSc and inflammatory markers. ConclusionsBoth, PWV and AIx are dependent on MBP and age DAS28 may affect AIx in RA patients, while other disease or inflammatory markers are unlikely to have any effect. MBP is one of the main cardiovascular risk factors affecting the arterial stiffness in RA, SLE and SSc patients therefore controlling MBP in systemic rheumatic disease patients is mandatory.

Anticentromere antibody-positive primary Sjögren's syndrome: Epitope analysis of a subset of anticentromere antibody-positive patients

Objectives: Anticentromere antibody (ACA) is generally considered to be a serological marker for systemic sclerosis (SSc). ACA-positive patients with primary Sjögren's syndrome (pSS) have also been reported. ACA often recognizes centromere proteins (CENPs): CENP-A, CENP-B, and CENP-C, and sometimes reacts to heterochromatin protein 1 (HP1)α. We compared the reactivity against six different epitopes for three ACA-positive clinical subgroups: 29 patients with pSS, 36 SSc patients with sicca symptoms, and 28 SSc patients without sicca symptoms.Methods: We utilized enzyme-linked immunosorbent assays (ELISAs) with recombinant proteins covering six different epitope regions of ACA (the amino terminus (Nt) of CENP-A, CENP-B, and CENP-C, the carboxyl terminus (Ct) of CENP-B and CENP-C, and HP1α).Results: The patients with pSS were found to have IgG-class autoantibodies against CENP-C-Nt and HP1α, and IgA-class autoantibodies against CENP-C-Ct with significantly higher frequencies than the SSc patients with or without sicca symptoms. The positive predictive value and the negative predictive value of the combination of these three autoantibodies for pSS were 73% and 82%, respectively, for pSS.Conclusions: Based on the result that reactivities against CENP-C and HP1α in patients with pSS differ from those in patients with SSc, we propose ACA-positive pSS as a clinical subset of SS that is independent of SSc.

Comparison of clinical and serological parameters in female and male patients with systemic sclerosis.

ObjectivesThe course of systemic sclerosis (SSc) can differ in female and male patients. According to the literature the incidence rates of diffuse cutaneous SSc, scleroderma renal crisis and digital ulceration are higher in male patients. The aim of the study was to compare selected clinical and serological parameters in male and female patients with SSc.Material and methodsThe study encompassed 101 European Caucasian patients with SSc, including 23 men, hospitalized in the Department of Rheumatology. Patients fulfilled the American Rheumatism Association (ARA) classification criteria for SSc. The study groups of men and women were assessed according to the SSc subtype, incidence of internal organ involvement and presence of antinuclear antibodies considered SSc markers.ResultsDiffuse cutaneous (dc) SSc was observed more commonly in men than in women (13/23 vs. 25/78; p = 0.03). The time from the development of Raynaud's phenomenon to the diagnosis was significantly shorter in male compared to female patients (3.2 ±4.7 vs. 7.5 ±7.1; p = 0.01). The incidence of scleroderma renal crisis (SRC) was significantly higher (3/23 vs. 2/78; p = 0.04) and of other calcifications significantly lower in the male group compared to the female group (1/23 vs. 20/78; p = 0.02).ConclusionsWe concluded that the incidence of dcSSc is higher in men compared to women. The time from the development of Raynaud's phenomenon to the diagnosis is shorter in the male compare to female group. The incidence of SRC is higher, whereas that of calcifications is lower in SSc men. The serological profiles of female and male patients with SSc are comparable.

Increased plasma soluble urokinase plasminogen activator receptor levels in systemic sclerosis: possible association with microvascular abnormalities and extent of fibrosis.

Urokinase plasminogen activator receptor (uPAR) is a key component of the fibrinolytic system involved in extracellular matrix remodeling and angiogenesis. Novel animal models supported the key role of uPAR not only in fibrosis but also in systemic sclerosis (SSc)-related microvascular abnormalities. The aim of this study was to investigate plasma soluble uPAR (suPAR) levels in SSc, and their association with organ-specific involvement. suPAR concentrations were measured by ELISA in SSc patient (n=83) and in healthy controls (n=29). Simultaneously, CRP and ESR were assessed. Detailed clinical data including skin, lung, heart and microvascular characteristics were evaluated at sampling. suPAR values were higher in SSc patients than in controls. Subgroup analysis showed higher suPAR values in diffuse cutaneous- than in limited cutaneous SSc and correlated with anti-Scl-70+. suPAR levels also associated with pulmonary function test parameters of fibrosis, presence of microvascular lesions (e.g., Raynaud phenomenon, naifold capillaroscopic abnormalities and digital ulcers) and arthritis. Our data indicate that suPAR might be a valuable early diagnostic marker of SSc which also correlates with disease severity.

Possible single-nucleotide polymorphism loci associated with systemic sclerosis susceptibility: a genetic association study in a Chinese Han population.

ObjectiveThe aim of this study was to confirm the association of RHOB and FAM167A-BLK gene polymorphisms with susceptibility to systemic sclerosis (SSc) in a Chinese Han population.MethodsA total of 248 SSc patients and 251 healthy controls of Chinese Han ethnicity, which visited the department of dermatology of Peking Union Medical College Hospital, were included in the study. Six selected single nucleotide polymorphisms (SNPs) in the RHOB and FAM167A-BLK regions were selected as markers and were genotyped using a MassARRAY system, which is based on the matrix-assisted laser desorption/ionization time of flight mass spectrometry technique.ResultsThree SNPs in the coding regions of the RHOB and FAM167A-BLK genes displayed an association with SSc: (1) rs1062292T, which is a newly discovered SNP in the RHOB gene (P = 0.03, odds ratio [OR] = 1.62, 95% confidence interval (CI) = 1.05–2.50), (2) rs2736340T (P = 0.03, OR = 1.39, 95%CI = 1.03–1.85), and (3) rs13277113A (P = 0.04, OR = 1.34, 95%CI = 1.01–1.76), both in the FAM167A-BLK gene. Our results support previous findings that vaiants in the RHOB and FAM167A-BLK genes may be associated with susceptibility to SSc. However, the loci of the SNPs in RHOB region that displayed an association with SSc are quite different from the loci which were identified in studies of Caucasian populations.ConclusionOur results confirm that RHOB and FAM167A-BLK polymorphisms exist in Chinese Han SSc patients. Therefore, variants of the RHOB and FAM167A-BLK genes are promising genetic markers for SSc.

AB0199 IGG Subclasses of Autoantibodies Directed against the Angiotensin Receptor Type 1 and the Endothelin Receptor Type A and their Clinical Relevance

BackgroundIgG4-related diseases are often characterized by a generalized inflammatory fibrosis which is also present in patients suffering from systemic sclerosis (SSc). Recent findings indicate the importance of autoantibodies (Aabs) against...

AB0618 Comparison of Selected Serological and Clinical Parameters in Female and Male Patients with Systemic Sclerosis

BackgroundThe course of systemic sclerosis (SSc) can differ in female and male patients. It has been suggested earlier that in male patients, the incidence rates of diffuse cutaneous SSc, scleroderma...

SP0179 Biological Changes in Early Systemic Sclerosis

Early systemic sclerosis (SSc) is a newly identified condition characterized by the association of Raynaud's phenomenon (RP) with SSc marker autoantibodies and/or with a scleroderma pattern at nailfold videocapillaroscopy (NVC),...

Early systemic sclerosis: serum profiling of factors involved in endothelial, T-cell, and fibroblast interplay is marked by elevated interleukin-33 levels.

To assess the serum profile of factors involved in endothelial, T-cell, and fibroblast interplay in patients with Raynaud's phenomenon (RP) associated with nailfold vodeocapillaroscopy (NVC) scleroderma findings and/or systemic sclerosis (SSc) marker autoantibodies, recently labeled as early SSc patients. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), CCL2, CXCL8, IL-13, IL-33, and transforming growth factor-β (TGF-β) were measured in 24 early SSc patients, 48 definite SSc patients, and 24 osteoarthritis/fibromyalgia controls by multiplex suspension immunoassay. All SSc patients were investigated for the presence/absence of preclinical and clinical organ involvement, SSc marker autoantibodies, and NVC abnormalities. Serum sICAM-1, CCL2, CXCL8, and IL-13 were increased in all SSc patients as compared to controls, and paralleled the severity of the disease subset (early SSc < limited cutaneous SSc < diffuse cutaneous SSc; p < 0.0001). Surprisingly, IL-33 was significantly higher in early SSc patients as compared to both controls (p < 0.01) and definite SSc patients (p < 0.05). In early SSc there were no differences in the investigated markers according to the functional and serological features assessed. Our study suggests that an endothelial, T-cell and fibroblast activation can be present in patients with early SSc and it is associated with a distinct profile of circulating factors involved in the cross-talk of these cells. The marked increase of IL-33 in early SSc patients suggests new routes of investigation of cell-cell dynamics in target tissues predating overt disease manifestations, thus opening to new therapeutic approaches.

Serum levels of soluble carbonic anhydrase IX are decreased in patients with diffuse cutaneous systemic sclerosis compared to those with limited cutaneous systemic sclerosis.

Hypoxia may play an important role in the pathogenesis of systemic sclerosis (SSc). Carbonic anhydrase IX (CA IX) is one of the hypoxia markers and its extracellular domain can be released into the serum. However, the clinical significance of serum CA IX levels in SSc is still unknown. The aim of this study is to evaluate the possibility that serum CA IX levels can be a specific disease marker of SSc. Serum samples were obtained from SSc patients and healthy controls. Patients diagnosed as scleroderma spectrum disorder (SSD), who did not fulfill the ACR criteria of SSc but were thought that they might develop SSc in the future, were also included in this study. Serum CA IX levels were measured with specific enzyme-linked immunosorbent assays. SSD patients had significantly lower CA IX levels than diffuse cutaneous SSc (dcSSc), limited cuntaneous SSc (lcSSc) and healthy control groups. Also, we found a significant decrease in the values in dcSSc patients compared to those of lcSSc patients. Serum levels of CA IX may be useful for the differentiation of lcSSc from SSD. Decreased serum CA IX levels in spite of the presence of hypoxia in SSc may indicate an impaired response to hypoxia, which leads to the persistent hypoxic condition. Our results suggest that the abnormal response to hypoxia may already exist in SSD patients, and may be involved in its pathogenesis.

What autoantibody tests should become widely available to help scleroderma diagnosis and management?

Anti-Th/To autoantibodies have been recognized as serological markers of systemic sclerosis (SSc) for more than 20 years. However, validated immunoassay kits to test this specificity have not been commercially available. SSc autoantibodies are basically mutually exclusive and are associated with a certain subset of the disease and/or with organ involvement. Anti-Th/To are generally considered to be markers of the limited cutaneous type of SSc with the involvement of certain internal organs. The excellent correlation between anti-Rpp25 as detected by their novel chemiluminescent method and anti-Th/To as detected by immunoprecipitation suggest that the new assays may become widely available tests for clinicians in future and could help to clarify the clinical significance of anti-Th/To in SSc as well as other conditions over different races or countries.

Early systemic sclerosis: short-term disease evolution and factors predicting the development of new manifestations of organ involvement.

IntroductionWe investigated early systemic sclerosis (SSc) (that is, Raynaud's phenomenon with SSc marker autoantibodies and/or typical capillaroscopic findings and no manifestations other than puffy fingers or arthritis) versus undifferentiated connective tissue disease (UCTD) to identify predictors of short-term disease evolution.MethodsThirty-nine early SSc and 37 UCTD patients were investigated. At baseline, all patients underwent clinical evaluation, B-mode echocardiography, lung function tests and esophageal manometry to detect preclinical alterations of internal organs, and were re-assessed every year. Twenty-one early SSc and 24 UCTD patients, and 25 controls were also investigated for serum endothelial, T-cell and fibroblast activation markers.ResultsAt baseline, 48.7% of early SSc and 37.8% of UCTD patients had at least one preclinical functional alteration (P > 0.05). Ninety-two percent of early SSc patients developed manifestations consistent with definite SSc (that is, skin sclerosis, digital ulcers/scars, two or more teleangectasias, clinically visible nailfold capillaries, cutaneous calcinosis, X-ray bibasilar lung fibrosis, X-ray esophageal dysmotility, ECG signs of myocardial fibrosis and laboratory signs of renal crisis) within five years versus 17.1% of UCTD patients (X2 = 12.26; P = 0.0005). Avascular areas (HR = 4.39 95% CI 1.18 to 16.3; P = 0.02), increased levels of soluble IL-2 receptor alpha (HR = 4.39; 95% CI 1.03 to 18.6; P = 0.03), and of procollagen III aminopropeptide predicted disease evolution (HR = 4.55; 95% CI 1.18 to 17; P = 0.04).ConclusionMost early SSc but only a few UCTD patients progress to definite SSc within a short-term follow-up. Measurement of circulating markers of T-cell and fibroblast activation might serve to identify early SSc patients who are more likely to develop features of definite SSc.

Identification of new autoantibody specificities directed at proteins involved in the transforming growth factor β pathway in patients with systemic sclerosis

IntroductionAntinuclear antibodies (ANAs), usually detected by indirect immunofluorescence on HEp-2 cells, are identified in 90% of patients with systemic sclerosis (SSc). Thus, approximately 10% of SSc patients have no routinely detectable autoantibodies, and for 20% to 40% of those with detectable ANAs, the ANAs do not have identified specificity (unidentified ANAs). In this work, we aimed to identify new target autoantigens in SSc patients.MethodsUsing a proteomic approach combining two-dimensional electrophoresis and immunoblotting with HEp-2 cell total and enriched nuclear protein extracts as sources of autoantigens, we systematically analysed autoantibodies in SSc patients. Sera from 45 SSc patients were tested in 15 pools from groups of three patients with the same phenotype. A sera pool from 12 healthy individuals was used as a control. Proteins of interest were identified by mass spectrometry and analysed using Pathway Studio software.ResultsWe identified 974 and 832 protein spots in HEp-2 cell total and enriched nuclear protein extracts, respectively. Interestingly, α-enolase was recognised by immunoglobulin G (IgG) from all pools of patients in both extracts. Fourteen and four proteins were recognised by IgG from at least 75% of the 15 pools in total and enriched nuclear protein extracts, respectively, whereas 15 protein spots were specifically recognised by IgG from at least four of the ten pools from patients with unidentified ANAs. The IgG intensity for a number of antigens was higher in sera from patients than in sera from healthy controls. These antigens included triosephosphate isomerase, superoxide dismutase mitochondrial precursor, heterogeneous nuclear ribonucleoprotein L and lamin A/C. In addition, peroxiredoxin 2, cofilin 1 and calreticulin were specifically recognised by sera from phenotypic subsets of patients with unidentified ANAs. Interestingly, several identified target antigens were involved in the transforming growth factor β pathway.ConclusionsWe identified several new target antigens shared among patients with SSc or specific to a given phenotype. The specification of new autoantibodies could help in understanding the pathophysiology of SSc. Moreover, these autoantibodies could represent new diagnostic and/or prognostic markers for SSc.

Serum levels of soluble CD163 in patients with systemic sclerosis

Macrophages may play a role in the pathogenesis of systemic sclerosis (SSc), and CD163-positive M2 macrophages are potentially important source for fibrosis-inducing cytokines. However, no link between M2 macrophages and SSc has been established. The aim is to evaluate the possibility that serum levels of soluble CD163 (sCD163) can be a useful marker for SSc, reflecting M2 activation of macrophages in this disease. Serum sCD163 levels of 43 patients with SSc, 10 patients with scleroderma spectrum disorder (SSD), and 12 healthy controls were measured with specific enzyme-linked immunosorbent assays. SSc patients had significantly higher serum sCD163 levels than healthy controls. The sCD163 levels in SSD patients were higher than healthy controls and lower than SSc patients. Significantly higher right ventricular systolic pressure and lower % DLco levels, and shorter duration of disease were seen in SSc patients with elevated serum sCD163 levels than those with normal levels. These results suggest that sCD163 levels may be increased in proportion to the progression of this disease, indicating the involvement of CD163 in the pathogenesis of SSc. Furthermore, serum sCD163 levels may be a marker of pulmonary hypertension at the early stage in patients with SSc.