Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Imbalanced serum levels of Ang1, Ang2 and VEGF in systemic sclerosis: Integrated effects on microvascular reactivity.

Introduction and aim: Microangiopathy is a hallmark of systemic sclerosis (SSc). It is a progressive process from an early inflammatory and proangiogenic environment to insufficient microvascular repair with loss of microvessels. The exact underlying mechanisms remain ill-defined. Aim of the study was to investigate whether imbalanced angiopoietins/VEGF serum profile should be related in SSc to the altered microvascular reactivity characterized by aberrant angiogenesis and avascularity. Materials and methods: Serum levels of Angiopoietin-1 (Ang1), Angiopoietin-2 (Ang2) and VEGF were measured by ELISA in 47 SSc patients and 27 healthy controls. Microvascular alterations were assessed by nailfold videocapillaroscopy (NVC). Results: Serum concentrations of Angl were significantly lower [mean (S.D.): 21516.04 (11,441.035) pg/ml], and Ang2 significantly increased [25,89.55 (934.225) pg/ml] in SSc as compared with the control group [Ang1: 28,457.08 (10,431.905) pg/ml; Ang2: 1556.23 (481.255) pg/ml, p < 0.01, respectively], whereas VEGF did not differ significantly. The ratios of Ang1/Ang2 and Ang1/VEGF were significantly lower in SSc patients (8.346 +/- 4.523 and 95.17 +/- 75.0, respectively) than in healthy subjects (17.612 +/- 6.731 p < 0.000001 and 183.11 +/- 137.73; p = 0.004]. Formation of giant capillaries with vascular leakage and collapse was associated with significant increase in VEGF and concomitant Ang1 deficiency. Capillary loss was related to significant increase in VEGF with respect to those with preserved capillary number (395.12 +/- 256.27 pg/mL vs. 254.80 +/- 213.61 pg/mL) whereas elevated Ang2 levels induced more advanced capillary damage as indicated by the presence of the "Late" NVC pattern. Conclusions: We found that serum levels of Ang1, Ang2 and VEGF are differentially expressed in SSc and altered Ang1/Ang2 profile might underlay the aberrant angiogenesis in SSc despite increase in VEGF. For the first time we identified that significant deficiency of Ang1 might be involved in early capillary enlargement, followed by collapse and lack of stable newly-formed vessels in VEGF-enriched environment, whereas Ang2 levels seem to increase later in disease progression and advanced microvascular damage ("Late" NVC pattern)

Evaluation of serum concentrations of the selected cytokines in patients with localized scleroderma

Introduction : Localized scleroderma is an autoimmune disease primarily affecting the skin. The cause of disease remains unexplained although environmental factors are implicated, which are likely to be responsible for activation of the endothelium and subsequent inflammation leading to excessive synthesis of collagen and extracellular matrix components. Aim: To determine concentrations of interleukin (IL)-27, transforming growth factor (TGF)-β1, TGF-β2, IL-6, and sIL-6R in patients with localized scleroderma compared to controls and to assess the relations between their levels and laboratory markers. Material and methods: The study encompassed 17 females with localized scleroderma (aged 25–67). The control group consisted of 30 age-matched healthy women. The blood was sampled from the basilic vein. Serum levels of cytokines were determined using ELISA. Results : The TGF-β2 levels were found to be significantly lower in patients with localized scleroderma compared to controls. Concentrations of TGF-β1 were decreased in scleroderma patients when compared to controls but without statistical significance. There were no significant differences in serum IL-6, sIL-6R and IL-27 levels between patients and the control group; however, we found a significant positive correlation between the level of sIL-6 and ESR among subjects with localized scleroderma. Conclusions : The findings of decreased serum levels of TGF-β1 and TGF-β2 in patients with localized scleroderma demonstrate a possible association of these cytokines with pathogenesis of the disease. The results suggest also that sIL-6R is likely to be involved in inflammation in patients with localized scleroderma

Plasma endothelial microparticles reflect the extent of capillaroscopic alterations and correlate with the severity of skin involvement in systemic sclerosis.

Introduction and aim Endothelial microparticles (EMPs) are membrane-coated vesicles shed from endothelial cells and are considered markers of the endothelial state. It has been shown that total numbers of circulating EMPs are increased in patients with systemic sclerosis (SSc), but their clinical correlations have not yet been investigated in detail. We aimed to assess possible relationships between circulating EMPs and clinical as well as laboratory features among SSc patients with special attention to possible association with alteration in microvascular morphology objectified on nailfold videocapillaroscopy and clinical signs of microvascular complications. Materials and methods The study included 47 SSc patients and 27 age- and sex-matched healthy controls. EMPs were identified with flow cytometry after staining platelet-poor plasma with combinations of fluorescent cell-specific monoclonal antibodies (anti-CD31, -51, -42b, -62E and Annexin V). The following types of EMPs were evaluated: total EMPs (CD31 +/CD42b 12), activated EMPs (CD62E +/AnnV 12,) and apoptotic EMPs (CD62E +/AnnV + or CD51 +). Clinical evaluation of patients was obtained, including nailfold videocapillaroscopy. Results All types of EMPs were significantly elevated in SSc patients as compared with healthy controls. We found significant inverse correlation between severity of skin involvement and values of total EMPs (r = 12 0.32; p = 0.02) and their levels tended to be lower in SSc patients with digital ulcers when compared to those without ischaemic skin lesions (p = 0.09). Total EMPs and activated EMPs showed correlations with the number of ramified capillaries (r = 12 0.40 and r = 0.37, respectively, p &lt; 0.05 for both). Moreover, total EMPs inversely correlated with the severity of capillary loss (r = 12 0.35, p &lt; 0.05) and their levels were significantly lower in patients with late NVC pattern with respect to those with early microangiopathy (p &lt; 0.05). On the other hand, active NVC pattern was characterized by strongly elevated levels of activated EMPs when compared to an early vascular alteration (p &lt; 0.05). Conclusions Our results suggest that quantity and phenotype of circulating EMPs might indicate on molecular vascular damage with endothelial dysfunction and to reflect progressive loss of capillaries consequencing in microvascular insufficiency in SSc patient