Exploring the Role of Serum Osteonectin and Hsp27 in Pediatric MAFLD Diagnosis and Cardiometabolic Health.

BACKGROUND: Childhood obesity is one of the major challenges of public health policies. The problem of fatty liver in childhood, known as MAFLD (metabolic dysfunction-associated fatty liver disease), is of particular interest as the gold standard diagnosis technique is invasive (liver biopsy). Hence, efforts are made to discover more specific biomarkers for the MAFLD signature. Therefore, the aim of the study was to evaluate Osteonectin and Hsp27 as biomarkers for MAFLD diagnosis and to assess their links with auxological and biochemical profiles of overweight and obese pediatric subjects. METHODS: A cross-sectional study in which we (re)analyzed data from the MR PONy cohort comprising 71 pediatric subjects. Auxological data, liver ultrasonography and biochemical serum profile were recorded. Lipid-derived indices and body composition indices were calculated. Nevertheless, serum Osteonectin and Hsp27 levels were assessed using an ELISA approach. RESULTS: MAFLD prevalence was 40.8%. Higher Osteonectin levels were noted in MAFLD subjects versus non-MAFLD subjects and in dyslipidemic children regardless of their liver function status. Lipid-derived indices had good diagnostic capacity for MAFLD. CONCLUSIONS: We confirm Osteonectin as a MAFLD diagnosis biomarker in children. Also, lipid-derived indices are useful as metabolic-associated organ impairment markers in children even before the onset of obesity.

Circulatory cytokeratin 17, marginal zone B1 protein and leucine-rich α2-glycoprotein-1 as biomarkers for disease severity and fibrosis in systemic sclerosis patients.

Introduction: Systemic sclerosis (Ssc) is a multiorgan debilitating autoimmune disease that associates the triad: vascular involvement, tissue fibrosis and profound immune response alterations. Numerous previous studies focused on identification of candidate proteomic Ssc biomarkers using mass-spectrometry techniques and a large number of candidate Ssc biomarkers emerged. These biomarkers must firstly be confirmed in independent patient groups. The aim of the present study was to investigate the association of cytokeratin 17 (CK17), marginal zone B1 protein (MZB1) and leucine-rich α2-glycoprotein-1 (LRG1) with clinical and biological Ssc characteristics. Material and methods: Serum CK17, MZB1 and LRG1 were assessed in samples of the available Ssc biobank comprising of samples from 53 Ssc patients and 26 matched age and gender controls. Results: Circulatory CK17, LRG1 and MZB1 concentrations were increased in Ssc patients. Cytokeratin 17 is independently associated with Ssc disease activity. Patients with pulmonary fibrosis expressed higher LRG1 and MZB1 concentrations. Serum MZB1 concentrations were also associated with extensive skin fibrosis. Conclusions: Serum CK17, MZB1 and LRG1 were confirmed biomarkers for Ssc. LRG1 seems a good biomarker for pulmonary fibrosis, while MZB1 is a good biomarker for extensive skin fibrosis. CK17 proved to be independently associated with Ssc disease severity, higher CK17 values being protective for a more active disease.

S100A6, Calumenin and Cytohesin 2 as Biomarkers for Cutaneous Involvement in Systemic Sclerosis Patients: A Case Control Study.

BACKGROUND: Systemic sclerosis (Ssc) is an autoimmune disease with incomplete known physiopathology. There is a high number of candidate proteomic biomarkers for Ssc that have not yet been confirmed on independent Ssc cohorts. The aim of the study was to confirm circulating S100A6, calumenin, and cytohesin 2 as biomarkers for Ssc. METHODS: 53 Ssc patients and 26 age- and gender-matched controls were included. Serum S100A6, calumenin, and cytohesin 2 were evaluated with commercial ELISA kits. Associations between serum expression and clinical Ssc characteristics were evaluated. RESULTS: Serum calumenin, S100A6, and cytohesin 2 were higher in Ssc patients compared to controls. Calumenin associated with extensive cutaneous fibrosis, frequency of Raynaud phenomenon, and low complement level, and had a tendency to be higher in Ssc patients with pulmonary fibrosis. S100A6 correlated with the number of active digital ulcers. Serum cytohesin 2 levels were higher in patients with teleangiectasia and associated with pulmonary artery pressure. CONCLUSIONS: Serum calumenin, S100A6, and cytohesin 2 were confirmed as biomarkers on an independent group of Ssc patients. Calumenin had the best predictive capacity for cutaneous Ssc manifestations. Future studies are needed to evaluate the prognostic value of these biomarkers and evaluate them as possible therapeutic targets.

Candidate proteomic biomarkers in systemic sclerosis discovered using mass-spectrometry: an update of a systematic review (2014-2020).

Background. Systemic sclerosis (Ssc) is an autoimmune disease characterized by graduate cutaneous and tissue fibrosis development and irreversible fibroproliferative vascular changes.The aim of the current systematic review was to update the list of proteomic candidate biomarkers identified from Ssc samples with mass spectrometry techniques.Methods. Medline and Scopus databases were searched on 1st September 2020. Relevant articles were searched from March 2014 until September 2020. Two independent reviewers evaluated the retrieved articles.Results. From a total of 97 articles, 9 articles were included in the final analysis summarizing 539 candidate proteomic biomarkers from various samples from Ssc patients (a larger number compared to the previous systematic review). Most biomarkers were identified from cutaneous biopsies. Only 5 articles included a validation step of the findings with only 13 biomarkers being validated.Conclusions. Although many candidate biomarkers were additionally identified, independent validation studies are needed in order to evaluate the importance of these biomarkers for Ssc patients.

Endocan and Lumican in Relation to Cardiometabolic Risk in a Pediatric Overweight and Obese Cohort: A Cross-Sectional Study.

The aim of the study was to evaluate serum Endocan and Lumican levels as biomarkers for pediatric Nonalcoholic Fatty Liver Disease (NAFLD) and to explore their associations with pediatric cardiometabolic risk factors. We conducted a cross-sectional study on 68 pediatric obese and overweight (O&O) patients. Ten healthy controls were recruited. Serum Lumican and Endocan levels were analyzed using ELISA kits. O&O patients had lower levels of Endocan compared to healthy controls (p < 0.001). There were no differences between serum Endocan levels in O&O patients with NAFLD and those without (p = 0.53). Patients considered having Nonalcoholic Steatohepatitis (NASH) had lower Endocan levels compared to O&O patients without NASH (p = 0.026). Patients with metabolic syndrome had lower levels of Endocan (p = 0.003). There were no significant differences between serum Lumican levels in O&O children compared to healthy controls. Lumican levels were higher in patients with hypertension (p = 0.04). In O&O patients, Lumican levels were negatively correlated with Endocan levels (r = -0.37, p = 0.002). Endocan seems a promising biomarker for the evaluation of pediatric NASH. Lumican was not confirmed as a biomarker for NAFLD in our cohort but was associated with higher arterial pressure. Low Endocan levels are accompanied by high serum Lumican levels, and this could be an early signature of cardiometabolic risk.

Circulating Hsp90 Isoform Levels in Overweight and Obese Children and the Relation to Nonalcoholic Fatty Liver Disease: Results from a Cross-Sectional Study.

BACKGROUND: Obesity prevalence is increasing in children. It is associated with various comorbidities including nonalcoholic fatty liver disease (NAFLD). Hsp90 isoforms were identified in previous proteomic studies as potential biomarkers for NAFLD. The aim of the study was to analyze circulating levels of Hsp90α and Hsp90ß in overweight and obese children. In addition, Hsp90α and Hsp90ß were evaluated as biomarkers for NAFLD in overweight and obese children. METHODS: 68 overweight and obese children and ten age- and gender-matched controls were recruited. Hsp90α and Hsp90ß levels were analyzed from serum in both controls and overweight and obese children by ELISA. RESULTS: Serum Hsp90ß and total Hsp90 levels were statistically significantly higher in overweight and obese children compared to controls. On the contrary, there was no difference in Hsp90α levels between overweight and obese children and healthy controls. Hsp90 isoforms had different expression in NAFLD patients. Hsp90ß levels were higher in overweight and obese NAFLD patients while Hsp90α levels were lower. Hsp90α to Hsp90ß ratio had better accuracy for NAFLD diagnosis in obese and overweight patients compared to individual biomarkers. CONCLUSION: Hsp90 isoforms were confirmed on an independent cohort as biomarkers for NAFLD in overweight and obese children. In these patients, it seems to be more useful to separately analyze Hsp90 isoforms rather than total Hsp90 as the isoforms have greater discriminative capacity.

Lipid profile pattern in pediatric overweight population with or without NAFLD in relation to IDF criteria for metabolic syndrome: a preliminary study.

BACKGROUND AND AIMS: The aim of this study is to assess the lipid profile pattern of pediatric overweight and/or obese patients with Non-Alcoholic Fatty Liver Disease (NAFLD) in relation to IDF Consensus Criteria for Metabolic Syndrome (MetS). MATERIAL AND METHODS: We conducted a cross-sectional preliminary study on 45 consecutive pediatric patients. Overweight or obese children aged from 3 to 18 years were included. Standardized measurement of blood pressure and anthropometric parameters were performed. Biological evaluation included inflammatory status, lipid profile, glycemic profile, full blood count and liver function tests. Abdominal ultrasound was performed in all patients. RESULTS: Prevalence of MetS was 44.4%. A number of 21 patients (46.7%) had NAFLD. MetS patients had higher risk for NAFLD (OR = 9.5, 95% CI = 2.42-37.24). Also patients with positive familial history of type 2 diabetes had a 6.61 fold higher risk for NAFLD (OR = 6.61, 95% CI = 1.74-25.1). We performed a subgroup analysis in patients under ten years old. Patients under the age of ten which had both NAFLD and MetS met more frequently the hypertriglyceride criterion. After adjusting for age and MetS presence, triglyceride levels independently associated with NAFLD (adjusted R square = 0.46, unstandardized B coefficient = 34.51, 95% CI = 4.01-65.02, p = 0.02). CONCLUSION: NAFLD obese patients had higher prevalence of MetS, higher BMI and particular lipid profile pattern. Triglyceride levels independently associated with NAFLD after adjusting for age and MetS presence. According to our findings we suggest early triglyceride testing (even below the age of ten) in selected patients.

IL-17 and Th17 cells in systemic sclerosis: a comprehensive review.

T cells (especially T helper cells) seem to be strongly associated with systemic sclerosis pathogenesis. Th17-IL-17 axis was proved to be involved in the pathogenesis of multiple autoimmune diseases. By performing a comprehensive research of the literature indexed in PubMed database, the current review summarizes current knowledge related to Th17 and IL-17 in systemic sclerosis. While there is promising data suggesting inhibition of Tregulatory and Th1 signals on one hand and promotion of Th17 and Th2 signals on the other, studies that include prospective and integrated analysis of Tregulatory, Th17, Th1, Th2 (cells and derived cytokines) on the same cohort of Ssc patients are warranted.