title: Increased messenger RNA levels of the mesenchymal cadherin-11 in the peripheral blood of systemic sclerosis patients correlate with diffuse skin involvement.
abstract: OBJECTIVE
  Cadherin-11 is a cell-cell adhesion molecule also involved in cellular migration and invasion. Experimental studies implicated this molecule in inflammatory arthritis and fibrosing conditions. Moreover, cadherin-11 protein is hyper-expressed on fibroblasts and macrophages in the skin of systemic sclerosis (SSc) patients, whereas the respective mRNA levels correlate with skin thickness. Herein, we searched for possible cadherin-11 expression also in cells that circulate in SSc peripheral blood.
  
  
  METHODS
  Cadherin-11 mRNA was quantified by real-time reverse transcription-polymerase chain reaction in 3 ml blood samples obtained from 71 SSc patients (aged 53±2 years, 65 women) and 35 control non-SSc patients with Raynaud's phenomenon.
  
  
  RESULTS
  Cadherin-11 mRNA transcripts were detected in blood samples from 39% of patients with diffuse SSc, versus 16% of those with limited SSc, versus 6% and 16% of patients with idiopathic or associated with other connective tissue diseases Raynaud's phenomenon, respectively (p=0.049). Cadherin-11 mRNA levels in SSc patients were increased by 3.74-fold comparing to controls (p=0.036). By multivariate logistic regression analysis we found that diffuse skin involvement correlated, independently of age, gender, disease duration, lung involvement, digital ulcers, inflammatory indices or anti-Scl-70 autoantibody presence, with cadherin-11 mRNA positivity (p=0.028), but also with increased cadherin-11 mRNA levels (≥3-fold of non-SSc levels, p=0.011).
  
  
  CONCLUSIONS
  Cadherin-11 may be hyper-expressed in the peripheral blood of diffuse SSc patients. Studies on the origin and possible pathogenic function of these circulating cells may shed light into the complex disease pathogenesis and further support the notion that cadherin-11 is a potential therapeutic target in SSc.
authors.affiliation: Rheumatology Unit, First Department of Propaedeutic and Internal Medicine; and Department of Experimental Physiology, Athens University Medical School, Greece.
authors.forename: Panagiotis F
authors.initials: PF
authors.lastname: Christopoulos
authors.affiliation: Rheumatology Unit, First Department of Propaedeutic and Internal Medicine, Athens University Medical School, Greece.
authors.forename: Vasiliki-Kalliopi
authors.initials: VK
authors.lastname: Bournia
authors.affiliation: Rheumatology Unit, First Department of Propaedeutic and Internal Medicine, Athens University Medical School, Greece.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Panopoulos
authors.affiliation: Department of Experimental Physiology, Athens University Medical School, Greece.
authors.forename: Aristeides
authors.initials: A
authors.lastname: Vaiopoulos
authors.affiliation: Department of Experimental Physiology, Athens University Medical School, Greece.
authors.forename: Michael
authors.initials: M
authors.lastname: Koutsilieris
authors.affiliation: Rheumatology Unit, First Department of Propaedeutic and Internal Medicine, Athens University Medical School, Greece. psfikakis@med.uoa.gr.
authors.forename: Petros P
authors.initials: PP
authors.lastname: Sfikakis
mesh_terms: D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005819:Genetic Markers; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012333:RNA, Messenger / Q000097:blood*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D045743:Scleroderma, Diffuse / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D045745:Scleroderma, Limited / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D012720:Severity of Illness Index; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015820:Cadherins; D005819:Genetic Markers; D012333:RNA, Messenger; C086960:osteoblast cadherin