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Systemic sclerosis with multiple nodules: characterization of the extracellular matrix

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Abstract

Systemic sclerosis (SSc) is still an enigmatic disease of unknown etiology, although the pathophysiology is thought to be based on vascular alterations as well as immunological and fibrotic processes. Here we present the case of a female patient with diffuse SSc (dSSc), who developed multiple subcutaneous nodules. Histologic evaluation confirmed the diagnosis of nodular scleroderma, a very rare condition. Histological analysis of biopsies was combined with ultrastructural analysis by transmission electron microscopy and immunohistochemistry/immunofluorescence, using antibodies against different collagens and non-collagenous ECM proteins. Collagen fibrils were deposited at very high density in nodules as well as in adjacent extra nodular skin. Within nodules, a large fraction of immature collagen fibrils was detected with smaller and highly variable diameter. Activated fibroblasts were present, however no myofibroblasts were identified. Cartilage Oligomeric Matrix Protein (COMP), collagen XII and fibrillin-1 were all deposited at increased amounts within nodules and their distribution differed markedly from that in healthy skin. The excessive deposition of COMP within nodules closely resembled the distribution of COMP in keloids. Nodules—like keloids—were characterized by lack of myofibroblasts. By virtue of its structural properties and the capacity to avidly bind collagen I and XII, COMP is thought to reorganize and compact the collagen network, leading to a tissue with locally increased biomechanical tension acting on fibroblasts. In addition, COMP may present active TGFβ to fibroblasts. Both mechanisms in concert can activate fibroblast proliferation and production of extracellular matrix, resulting in a sustained activation loop.

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Acknowledgments

We thank Dick Heinegard (Lund), Lynn Sakai (Portland), Manuel Koch (Cologne) and Anja Saalbach (Leipzig) for generous gifts of antibodies and Angelika Arora (Cologne) for excellent technical help. This work was funded in part by Deutsche Forschungsgemeinschaft (DFG KR558/14-1 to TK and BE) and many thanks to all coauthors supporting this study. The work of Pia Moinzadeh was supported by a grant of the ADF (Arbeitsgemeinschaft Dermatologischer Forschung)/DDG (Deutsche Dermatologische Gesellschaft).

Conflict of interest

The authors declare no competing interest.

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Authors and Affiliations

  1. Department of Dermatology, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany

    P. Moinzadeh, P. Agarwal, N. Hunzelmann, B. Eckes & T. Krieg

  2. Department of Molecular and Cellular Sport Medicine, German Sport University, Cologne, Germany

    W. Bloch

  3. Department of Dermatology, Royal Free Hospital, Medical School, UCL, London, UK

    C. Orteu

  4. Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated, Diseases (CECAD), University of Cologne, Cologne, Germany

    T. Krieg

  5. Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany

    T. Krieg

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  1. P. Moinzadeh
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  2. P. Agarwal
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Correspondence to P. Moinzadeh.

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P. Moinzadeh and P. Agarwal are the combined first authorship.

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Moinzadeh, P., Agarwal, P., Bloch, W. et al. Systemic sclerosis with multiple nodules: characterization of the extracellular matrix. Arch Dermatol Res 305, 645–652 (2013). https://doi.org/10.1007/s00403-013-1383-0

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  • DOI: https://doi.org/10.1007/s00403-013-1383-0

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