Cadherin-11 mRNA transcripts are frequently found in rheumatoid arthritis peripheral blood and correlate with established polyarthritis

Abstract

Rheumatoid arthritis (RA) synovial fibroblasts hyperexpress the mesenchymal cadherin-11, which is involved also in tumor invasion/metastasis, whereas anti-cadherin-11 therapeutics prevent and reduce experimental arthritis. To test the hypothesis that cadherin-11 is aberrantly expressed in RA peripheral blood, 100 patients (15 studied serially) and 70 healthy controls were analyzed by real-time reverse transcription-PCR. Cadherin-11 mRNA transcripts were detected in 69.2% of moderately/severely active RA, versus 31.8% of remaining patients (p=0.001), versus 17.1% of controls (p<0.0001). Notably, cadherin-11 positivity correlated significantly and independently only with established (>1year) polyarthritis (>4 swollen tender joints), by multivariate logistic regression analysis including various possible clinical/laboratory factors. Rare cells of undefined nature, detected by flow cytometry following CD45(-) enrichment, strongly expressed surface cadherin-11 (estimated 10-50cells/ml of blood) in 5/6 patients with polyarticular established disease versus 1/6 patients with early RA. Studies on the potential pathogenic role of circulating cells expressing cadherin-11 in RA are warranted.

Review: The Tumor‐Like Phenotype of Rheumatoid Synovium: Molecular Profiling and Prospects for Precision Medicine

“…Cdh11 ‐deficient mice have hypoplastic synovia and show reduced inflammation and cartilage erosion when challenged in an inflammatory arthritis model. Cadherin 11 is minimally expressed in immune cells , and anti–cadherin 11 antibody reduces arthritis severity in mice . A humanized monoclonal antibody targeting cadherin 11 has been evaluated in a phase I tolerability study (Table ).…”

Cadherin‐11 (CDH11) expression in the peripheral blood of patients with active Multiple Myeloma

“…As suggested recently, mesenchymal CDH11 may drive migration of solid tumours to the bone and trigger osteoclastogenesis via homophylic interactions of cancer cells with osteoblasts and other bone marrow (BM) stromal cells (Shiirevnyamba et al , ). More recently, we reported that CDH11 might be expressed on rare circulating cells of haematopoietic origin in the peripheral blood (Sfikakis et al , ).…”

“…CDH11 mRNA expression was determined in myeloma cell lines (L363, JJ‐N3, MR20 and H92), as well as in samples from MM patients’ blood (3 ml), as previously described (Sfikakis et al , ). Forty‐two patients with symptomatic MM, of whom 10 were examined serially, were studied.…”

Research progress in the role and mechanism of Cadherin-11 in different diseases

“…Proinflammatory cytokines upregulate CDH11, and then promote FLS homophilic interaction mediated by CDH11, leading to inflammation aggravation and diffusion [22]. CDH11 is a potential therapeutic target for RA [28]. However, another study showed that CDH11 targeting regimen was not suitable for RA treatment [29].…”