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Lipocalin‐2 is expressed by activated granulocytes and keratinocytes in affected skin and reflects disease activity in acne inversa/hidradenitis suppurativa
Author(s) -
Wolk K.,
Wenzel J.,
Tsaousi A.,
WitteHändel E.,
Babel N.,
Zelenak C.,
Volk H.D.,
Sterry W.,
SchneiderBurrus S.,
Sabat R.
Publication year - 2017
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.15424
Subject(s) - hidradenitis suppurativa , medicine , lipocalin , acne , pathogenesis , psoriasis , biomarker , pathology , phlebotomy , gastroenterology , immunology , disease , dermatology , biology , biochemistry
Summary Background Acne inversa ( AI )/hidradenitis suppurativa is a chronic inflammatory disease characterized by painful axillary, inguinal and perianal skin lesions with deep‐seated nodules, abscesses and fistulae. Objectives This study aimed to identify and characterize the key players in AI pathogenesis. Methods Epidemiological and anamnestic data for patients with AI were collected, and blood and skin samples were also taken. Healthy participants and patients with psoriasis served as controls. Assessment of samples and cultures of primary cells was performed by enzyme‐linked immunosorbent assay, quantitative polymerase chain reaction on reverse transcribed mRNA, and immunohistochemistry. Results Of 35 mediators quantified in the blood of patients with AI , lipocalin‐2 ( LCN 2) appeared as one of the most significantly upregulated parameters compared with healthy participants [85·8 ± 12·2 ( n = 18) vs. 41·8 ± 4·2 ( n = 15); P < 0·001]. Strongly elevated LCN 2 expression was present in AI lesions, with granulocytes and keratinocytes being sources of this expression. In vitro , these cells upregulated LCN 2 production in response to tumour necrosis factor ( TNF )‐α, and a positive relationship between systemic TNF ‐α and LCN 2 levels ( r s = 0·55, P = 0·011; n = 20) was evident for AI . LCN 2 blood levels correlated with AI disease severity ( r s = 0·65, P < 0·001; n = 29), but not with disease duration, age, sex, body mass index or smoking habit. Detailed analyses revealed a link with the number of skin regions containing nodules and fistulae, but not scars. Conclusions LCN 2 might serve as a blood biomarker for the objective assessment of inflammatory activity in AI . We suggest a self‐amplification loop comprising TNF ‐α, neutrophilic granulocytes and LCN 2, which contributes to the recurrent skin neutrophil infiltration in AI , clinically evident as pus.