Characterisation of the inflammatory response in Dupuytren’s disease

Abstract

Background: Dupuytren’s disease is characterised by fibrotic nodule and cord formation in the palmar aponeurosis. The pathophysiology of the disease is still unknown, although cell stress and subsequent activation of immune mechanisms seems to be crucial. Materials and methods: Surgically obtained tissue and blood samples of 100 Dupuytren patients were processed by immunohistochemistry, flow cytometry, as well as immunoscope analysis. Macroscopically normal aponeurotic tissue served as control. Results: Locally, microvascular alterations and massive infiltration by mononuclear cells (CD3+, CD4 > CD8, CD45RO > CD45RA, S100 protein, CD56, CD68, scarce CD19 and mast cells) forming perivascular clusters were found in DD tissue. Cytokine profiling of fibromatosis tissue-derived T-cells showed a Th1/TH17-weighted immune response. Immunoscope analysis revealed a restricted T-cell receptor α/β repertoire pointing to an (auto)antigen-driven process. Conclusion: The striking accumulation of immune cells, expression of leukocyte adhesion molecules, as well as pro-inflammatory and pro-fibrotic cytokines near markedly narrowed vessels supports the theory that the abnormal proliferation of fibroblasts and production of extracellular matrix proteins in DD seems to be related to immune-mediated microvascular damage. The restricted T-cell receptor repertoire of intra-lesional T-cells points to an antigen-driven process. T-cells seem to play an important role in the development of Dupuytren’s disease.

Key Words:

• Palmar fibromatosis
• immune cells
• inflammation

Acknowledgements

The authors acknowledge the Lore-and-Udo-Saldow Donation, the Competence Centre Medicine Tyrol, and the Medizinischer Forschungsfonds Tirol for supporting the project.

We thank Sandra Hussl, Christoph Grabmer, Brigitte Jenewein, Andrea Eigentler, Michael Keller, Daniela Niederwieser, Ruth Pfeilschifter, and Harald Niederegger for technical support, and Dr Bettina Zelger for help with Dupuytren’s sample staging. Thanks also to Dr Ling Toh, Dr Otto Majdic, and Dr E. Liehl for supplying antibodies and recombinant IL-2. Dr Hanno Ulmer and Dr Richard Pfaringer supported the statistical evaluation of data.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.