Th17-Gene Expression Profile in Patients with Chronic Venous Disease and Venous Ulcers: Genetic Modulations and Preliminary Clinical Evidence
Rosario Amato,
Vincenzo Dattilo,
Carolina Brescia,
Lucia D’Antona,
Rodolfo Iuliano,
Francesco Trapasso,
Nicola Perrotti,
Davide Costa,
Nicola Ielapi,
Francesco Aiello,
Michele Provenzano,
Umberto Marcello Bracale,
Michele Andreucci,
Raffaele Serra
Affiliations
Rosario Amato
Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
Vincenzo Dattilo
Medical Genetics Unit, University Hospital “Mater Domini” of Catanzaro, 88100 Catanzaro, Italy
Carolina Brescia
Department of Experimental and Clinical Medicine, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
Lucia D’Antona
Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
Rodolfo Iuliano
Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
Francesco Trapasso
Medical Genetics Unit, University Hospital “Mater Domini” of Catanzaro, 88100 Catanzaro, Italy
Nicola Perrotti
Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
Davide Costa
Department of Law, Economics and Social Science, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
Nicola Ielapi
Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, Department of Surgical, Medical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
Francesco Aiello
Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
Michele Provenzano
Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
Umberto Marcello Bracale
Department of Public Health, University of Naples “Federico II”, 80138 Naples, Italy
Michele Andreucci
Department of Health Sciences, University of Catanzaro, 88100 Catanzaro, Italy
Raffaele Serra
Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, Department of Surgical, Medical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
Chronic venous disease is a condition globally widespread, resulting in a disabling pathological disorder. The CD4 + Th17+ (Cluster Differentiation 4) lymphocytes represent a regulative factor for innate immunity related to the development of complex diseases. Recently, these mechanisms have been associated with vascular disease. The aim of this work is to validate whether the Th17 response correlates with the development of CVI (Chronic venous insufficiency)and CVLUs (chronic venous limbs ulcers) and whether Th17 markers can be used, both as intrinsic risk factors and diagnostic markers, for disease development. PBL derived from peripheral blood samples of patients and controls were subjected to gene expression analysis for IL23R, IL17, SGK1, TGFβ, RORγ, FOXO1, and RANBP1 by qRT-PCR and immunoblot. A post hoc correlation, the diagnostic performance of the target genes, and multivariable analyses were properly conducted. The main expression markers of the CD4 + Th17+ switch were strongly activated in chronic venous insufficiency and in advanced ulceration. The correlation analysis demonstrated the inter-dependence on Th17’s signature modulation. ROC (Receiver Operating Characteristic) analysis defined, for the examined genes, a clinical value as the potential diagnostic markers. Multi-logistic regression studies showed that Th17 markers behave as empirical risk factors for CVD (chronic venous disease) development. Taken together, the present data provide a new hypothesis for the TH17-dependent pathogenesis of CVD, favoring the possibility for the development of new diagnostic, preventive, and therapeutic approaches.
