Role of kinurenic acid in the systemic sclerosis renal involvement.

Systemic sclerosis (SSc) subclinical renal vasculopathy is characterized by progressive increase of intrarenal stiffness and reduction of parenchymal thickness due to post ischemic fibrosis secondary to the renal Raynaud phenomenon. Aims of this study were to evaluate kinurenic acid (KYNA) serum level in SSc patients and healthy controls (HC) and to assess the role of KYNA in SSc subclinical nephropathy. Serum level of KYNA was evaluated in 52 SSc patients and 20 HC, matched for sex and age. Renal function was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (eGFR) and renal doppler ultrasound was performed to evaluate kidneys' morphology and indices of intrarenal stiffness. The parameters registered were renal longitudinal length, atrophy index (AI), renal sinus, parenchymal thickness, renal resistive index (RRI), pulsatile index (PI) and systolic/diastolic ratio (S/D). SSc patients had lower median value of KYNA than HC [54.43 ng/ml (IQR 44.44-63.64) vs 61.94 ng/ml (IQR 55.23-88.75), p < 0.001]. SSc patients with AI ≥ 0.70 had lower KYNA than SSc patients with AI < 0.70 [47.85 ng/ml (IQR 41.16-59.91) vs 55.5 ng/ml (IQR 49.99-67.33), p < 0.05] and a slightly significant negative linear correlation was found between KYNA and AI (r = - 0.249, p < 0.05). SSc patient with RRI ≥ 0.70 had higher KYNA than SSc patients with RRI < 0.70 [58.25 ng/ml (IQR 50.49-69.68) vs 50.07 ng/ml (IQR 42.70-56.31), p < 0.05] and a significant positive correlation was found between KYNA and RRI (r = 0.318, p < 0.05). KYNA may be used as a marker to evaluate the renal involvement in SSc patients.

Interleukin-33 and soluble suppression of tumorigenicity 2 in scleroderma cardiac involvement.

Interleukin (IL)-33 is part of the IL-1 family of cytokines and soluble suppression of tumorigenicity 2 (sST2) is part of the family of IL-1 receptors. In systemic sclerosis (SSc), IL-33 and sST2 are involved in cardiac manifestations such as diastolic dysfunction (DD), autonomic dysfunction (AD) and right ventricular-pulmonary arterial coupling assessed by tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP). Serum levels of IL33 and sST2 were assessed in 50 SSc patients and 14 healthy controls (HC). Clinical assessment, echocardiography and heart rate variability (HRV) analysis were performed in SSc patients. Serum levels of IL-33 and sST2 were significantly higher in SSc patients than HC. A linear positive correlation between modified Rodnan skin score and IL33 was observed. Serum values of sST2 were higher in SSc patients with DD than in patients without DD [15403 pg/ml (12,208-19,941) vs 8556 pg/ml (6820-11,036), p < 0.001]. sST2 showed a negative correlation with standard deviation of normal-to-normal RR intervals (SDNN) (r = - 0.281, p < 0.05) and positive correlation with low frequency/high frequency (LF/HF) (r = 0,349, p < 0.01). Negative linear correlation exists between sST2 and TAPSE/sPAP (r = - 0.398, p < 0.01). Serum levels of IL-33 and sST2 are higher in SSc patients than HC. Serum levels of sST2 are a potential marker of DD, AD and right ventricular-pulmonary arterial coupling.

IL33 and sST2 serum level in systemic sclerosis microvascular involvement.

AIM: Endothelial dysfunction and microvascular damage are hallmarks of systemic sclerosis (SSc). Objective of this study was to evaluate IL33 and ST2 serum levels in SSc patients and healthy controls (HC). Secondary aim was to evaluate the IL33 axis in the SSc microvascular manifestation. METHODS: IL33 and sST2 have been assessed in 46 SSc patients and 24 HC matched for sex and age. Main clinimetric indexes were assessed. Skin perfusion of hands was evaluated by Laser Speckle Contrast Analysis (LASCA) and echocolordoppler ultrasound of renal arteries was performed to evaluate subclinical renal involvement. RESULTS: SSc patients had higher serum level of IL33 and sST2 than HC. IL33 and sST2 were significantly higher in SSc patient with digital ulcers (DUs) compared to SSc patients without DUs. SSc patients with late nailfold videocapillaroscopy (NVC) pattern had higher serum levels of sST2 than SSc patients with active NVC pattern. SSc patients without proximal-distal gradient (PDG) at LASCA had significantly higher sST2 serum level compared to SSc patients with PDG. SSc patients with renal resistive index (RRI) ≥ 0.70 had higher serum levels of sST2 than SSc patients with RRI < 0.70. A positive linear correlation was shown between sST2 and RRI, between sST2 and intrarenal S/D and between sST2 and PI. Kaplan-Meier curves show a significantly reduced free survival from DUs in patients with increased sST2 (p = 0.025). In multivariate analysis, sST2 is associated with the development of new DUs. CONCLUSION: IL33 and sST2 are increased in SSc patients and ST2 might be a marker of microvascular damage.

Symptoms related to gastrointestinal tract involvement and low muscularity in systemic sclerosis.

INTRODUCTION/OBJECTIVES: Gastrointestinal tract (GIT) involvement is frequently observed in systemic sclerosis (SSc) and may lead to nutritional impairment. The aim of the study was to assess the prevalence of symptoms related to GIT involvement and to analyze the possible association between gastrointestinal symptoms and low muscularity in SSc patients. METHODS: Sixty-nine consecutive patients (60 females, median age 53 (IQR 43-63), body mass index (BMI) 23.2 (IQR 20.9-24.6) kg/m2) with diagnosis of SSc admitted to our Scleroderma Unit were enrolled. Clinical status, anthropometric data, and bioelectrical impedance (Inbody 770, USA) analysis-assessed Fat-Free Mass Index (FFMI) were recorded upon enrollment. UCLA questionnaire was used to quantify GIT involvement with seven specific scales. RESULTS: Mean FFMI was 16.2 kg/m2 (IQR 15.2-17.6). The median UCLA total score was 0.53 (IQR 0.19-0.89). FFMI showed a significant negative correlation with UCLA total score (r = -0.29, p = 0.016) and UCLA distention/bloating (r = -0.35, p < 0.01). In 16 patients (23.1%), FFMI was reduced and UCLA distention/bloating was significantly higher (p = 0.039) in SSc patients with lower FFMI [1.75 (IQR 0.75-2.12) vs 0.75 (IQR 0.25-1.75)]. At multiple linear regression model, FFMI showed association with UCLA distention/bloating [beta coefficient - 0.315 (95% CI of beta coefficient: -0.591; -0.039), p = 0.026], BMI [beta coefficient 0.259 (95% CI of beta coefficient: 0.163; 0.355), p = 0.001], and disease duration [beta coefficient - 0.033 (95% CI of beta coefficient: -0.059; -0.007), p = 0.015]. CONCLUSIONS: In SSc, low FFMI is associated with symptoms related to GIT involvement, in particular with distension/bloating. Key Points • FFMI is associated with symptoms related to GIT involvement. • Low FFMI is associated with symptoms related to UCLA distention/bloating. • Malnutrition is not associated with symptoms related to GIT involvement.

Metabolic syndrome and adipokine levels in systemic lupus erythematosus and systemic sclerosis.

INTRODUCTION: Aims of study were to evaluate the prevalence of metabolic syndrome (MetS) in systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) patients and to evaluate serum level of adipokines in SLE and SSc patients with and without MetS. METHODS: Fifty SLE patients and 85 SSc patients were enrolled. The diagnosis of MetS was made according to the criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III. Clinical assessment and serum levels of adiponectin and resistin were evaluate in SLE and SSc patients. RESULTS: Prevalence of MetS was significantly (p<0.0001) higher in SLE patients than SSc patients (36% vs 10.6%). Median values of resistin were significantly (p<0.001) higher in SLE patients with MetS than SLE patients without MetS [4.01 ng/mL (2.7-4.5) vs 1.92 ng/mL (1.2-3)]. Median values of adiponectin were significantly (p<0.05) lower in SLE patients with MetS than SLE patients without MetS [5.64 ng/mL (4.96-8) vs 8.38 ng/mL (6.54-11.01)]. Systemic Lupus Erythematosus Activity Index [8 (6-12) vs 10 (6-13), p<0.01] and Systemic Damage Index [2 (1-3) vs 2 (0-3), p<0.001] were significantly higher in MetS patients than in patients without MetS. In SSc, the median value of disease severity scale was significantly higher (p<0.05) in MetS patients than in patients without MetS [7 (5-7) vs 5 (3-6)]. CONCLUSION: Prevalence of MetS is higher in SLE patients. In SLE patients, MetS showed an association with adipokine levels and inflammation/activity disease scores. In SSc patients, MetS was associated with severity of disease. Key Points • Prevalence of metabolic syndrome is higher in SLE patients than SSc patients. • Resistin is higher in SLE patients with metabolic syndrome. • Adineponectin is lower in SLE patients with metabolic syndrome. • Disease severity scale is higher in SSc patients with metabolic syndrome.

Mycophenolate Mofetil Improves Exercise Tolerance in Systemic Sclerosis Patients with Interstitial Lung Disease: A Pilot Study.

INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune disease characterized by the overproduction of collagen leading to fibrosis of the skin and internal organs. Interstitial lung disease (ILD) is one of the major causes of death in patients with SSc. Exercise tolerance can be investigated by cardio-pulmonary exercise testing (CPET). First-line therapies in patients with SSc associated with ILD (SSc-ILD) include cyclophosphamide and mycophenolate mofetil (MMF). The aim of this study was to evaluate the response of patients with SSc-ILD to MMF by means of CPET. METHODS: Ten consecutive SSc patients were enrolled in this study. All SSc patients underwent clinical evaluation, echocardiography, pulmonary function tests, high-resolution computed tomography (HRCT) and CPET at baseline and after 2 years of therapy with MMF. RESULTS: After 24 months of treatment with MMF (target dose 1500 mg twice daily), forced vitality capacity, diffusing capacity of the lungs for carbon monoxide and systolic pulmonary arterial pressure had not improved significantly and there were no significant differences in HRCT findigns. In addition, peak oxygen uptake (V'O2 peak) and ventilatory equivalents for carbon dioxide production (V'E/V'CO2 slope) had not improved significantly. In contrast, there was a significant improvement from baseline to 24 months of treatment in the respiratory exchange ratio [median (interquartile range): 1.07 (0.92-1.22) vs. 1.26 (1.22-1.28), respectively; p < 0.01] and in the Borg scale for leg discomfort [median (interquartile range): 5 (5-7) vs. 4 (3-4), respectively; p < 0.01] . CONCLUSION: These data from our pilot study on a small cohort of SSc patients are the first to demonstrate that treatment with MMF can improves exercise tolerance and leg discomfort in patients with SSc-ILD. These preliminary results need to be confirmed in large randomized studies.