title: MMP8 Is Increased in Lesions and Blood of Acne Inversa Patients: A Potential Link to Skin Destruction and Metabolic Alterations.
abstract: Acne inversa (AI; also designated as hidradenitis suppurativa) is a chronic inflammatory disease with still unknown pathogenesis that affects the intertriginous skin of perianal, inguinal, and axillary sites. It leads to painful nodules, abscesses, and fistulas with malodorous secretion and is frequently associated with metabolic alterations. Here, we demonstrate that one of the most highly upregulated molecules in AI lesions is matrix metalloproteinase 8 (MMP8), an enzyme specialized in the degradation of extracellular matrix components and the HDL component apolipoprotein A-I. Granulocytes, which were present in AI lesions, secreted high amounts of MMP8 especially after TNF-αstimulation. Furthermore, activated fibroblasts but not keratinocytes were found to express MMP8. The high lesional MMP8 levels were accompanied by elevated blood levels that positively correlated with TNF-αblood levels and disease severity assessed by Sartorius score, especially with the number of regions with inflammatory nodules/abscesses and fistulas. Additionally, we found a negative correlation between blood MMP8 and HDL-cholesterol levels, suggesting a contributory role of MMP8 in metabolic alterations in AI. In summary, we demonstrate elevated MMP8 levels in AI lesions, suggest their role in skin destruction and metabolic alterations, and recommend the use of MMP8 as blood biomarker for AI disease activity assessment.
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany.
authors.forename: Athanasia
authors.initials: A
authors.lastname: Tsaousi
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany.
authors.forename: Ellen
authors.initials: E
authors.lastname: Witte
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, University Hospital Charité, Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Witte
authors.affiliation: Department of Dermatology and Allergy, University Hospital Charité, Berlin, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Röwert-Huber
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies, University Hospital Charité, Berlin, Germany; Institute of Medical Immunology, University Hospital Charité, Berlin, Germany.
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.affiliation: Department of Dermatology and Allergy, University Hospital Charité, Berlin, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, University Hospital Charité, Berlin, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wolk
authors.affiliation: Department of Dermatology and Allergy, University Hospital Charité, Berlin, Germany.
authors.forename: Sylke
authors.initials: S
authors.lastname: Schneider-Burrus
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany; Research Center Immunosciences, University Hospital Charité, Berlin, Germany.
authors.forename: Robert
authors.identifier: 0000-0002-0198-940X
authors.initials: R
authors.lastname: Sabat
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D008076:Cholesterol, HDL / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006098:Granulocytes / Q000166:cytology; D017497:Hidradenitis Suppurativa / Q000097:blood* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood* / Q000378:metabolism*; D008875:Middle Aged; D012867:Skin / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D014409:Tumor Necrosis Factor-alpha; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8