title: Site-specific immunophenotyping of keloid disease demonstrates immune upregulation and the presence of lymphoid aggregates.
abstract: 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.
  
  
  OBJECTIVE
  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 (n = 11) and normal scar (n = 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 (P < 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.
authors.affiliation: Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester M1 7DN, U.K.
authors.forename: R
authors.initials: R
authors.lastname: Bagabir
authors.forename: R J
authors.initials: RJ
authors.lastname: Byers
authors.forename: I H
authors.initials: IH
authors.lastname: Chaudhry
authors.forename: W
authors.initials: W
authors.lastname: Müller
authors.forename: R
authors.initials: R
authors.lastname: Paus
authors.forename: A
authors.initials: A
authors.lastname: Bayat
mesh_terms: D015415:Biomarkers; D001706:Biopsy; D016022:Case-Control Studies; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007627:Keloid / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology; D018709:Statistics, Nonparametric; D015854:Up-Regulation
chemical_list: D015415:Biomarkers