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Site-specific immunophenotyping of keloid disease demonstrates immune upregulation and the presence of lymphoid aggregates

Authors

  • R. Bagabir,

    1. Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester M1 7DN, U.K.
    2. Institute of Inflammation and Repair, University of Manchester, Manchester, U.K.
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  • R.J. Byers,

    1. Faculty of Medical and Human Sciences, School of Cancer and Enabling Sciences, Manchester Royal Infirmary, Manchester, U.K.
    2. Department of Histopathology, Central Manchester NHS Foundation Trust, Manchester, U.K.
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  • I.H. Chaudhry,

    1. Department of Histopathology, Central Manchester NHS Foundation Trust, Manchester, U.K.
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  • W. Müller,

    1. Faculty of Life Sciences, University of Manchester, Manchester, U.K.
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  • R. Paus,

    1. Institute of Inflammation and Repair, University of Manchester, Manchester, U.K.
    2. Department of Dermatology, University of Lübeck, Lübeck, Germany
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  • A. Bayat

    1. Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester M1 7DN, U.K.
    2. Institute of Inflammation and Repair, University of Manchester, Manchester, U.K.
    3. Manchester Academic Health Science Centre, University Hospital of South Manchester NHS Foundation Trust, Manchester, U.K.
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  • Funding sources
    R.B. is in receipt of support by an educational grant from the Ministry of Higher Education in Saudi Arabia. A.B. received a personal award from the NIHR (U.K.).

  • Conflicts of interest
    None declared.

Ardeshir Bayat.
E-mail: ardeshir.bayat@manchester.ac.uk

Abstract

Summary Background  Keloid disease (KD) is a common fibroproliferative disorder of unknown aetiology. T cells and macrophages are increased in KD and are thought to contribute to its pathogenesis. However, while a link between inflammation and fibrotic disorders is well known for other disorders, it remains undetermined in KD.

Objectives  Systematically to immunophenotype the inflammatory infiltrate of KD in situ in a site-specific manner, and to compare this with normal skin and scar tissue.

Methods  Sixty-eight keloid cases were screened for the presence of all three (intralesional, perilesional and extralesional) keloid-associated specific tissue sites. Subsequently, a complete set of 25 keloid biopsies (from different patients) was compared with normal skin (= 11) and normal scar (= 11) samples and subjected to systematic, site-specific quantitative immunohistomorphometry and histochemistry, using a range of immunological markers of B cells, T cells, macrophages, mast cells (MCs) and Langerhans cells.

Results  T cells, B cells, degranulated and mature MCs (coexpressing OX40 ligand) and alternative macrophages (M2) were all significantly increased in intralesional and perilesional KD sites compared with normal skin and scar tissue (< 0·05). Additionally, 10 of 68 KD cases (15%) showed the presence of distinctive lymphoid aggregates, which resembled mucosa-associated lymphoid tissue (MALT).

Conclusions  The increased number and activity of MCs and M2 may implicate inflammation in the fibrotic process in KD. The distinct KD-associated lymphoid aggregate resembles MALT, for which we propose the term ‘keloid-associated lymphoid tissue’ (KALT). It may perpetuate inflammatory stimuli that promote KD growth. KALT, MCs and M2 are promising novel targets for future KD therapy.

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