Lipocalin-2 is expressed by activated granulocytes and keratinocytes in affected skin and reflects disease activity in acne inversa / hidradenitis suppurativa

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 at the identification and characterization of key players in AI pathogenesis.

Methods

Epidemiologic and anamnestic data as well as blood and skin samples of AI patients were collected. Healthy participants and psoriasis patients served as controls. Assessment of samples and cultures of primary cells was performed by ELISA, qRT-PCR, and immunohistochemistry.

Results

Among 35 mediators quantified in blood of AI patients, lipocalin(LCN)-2 appeared as one of the most significantly upregulated parameters compared to healthy participants [85.8±12.2 (n=18) versus 41.8±4.2 (n=15); P=0.000]. Strongly elevated LCN2 expression was present in AI lesions, with granulocytes and, to a lower extent, keratinocytes being sources of this expression. In vitro, these cells upregulated LCN2 production in response to TNF-α, and a positive relationship between systemic TNF-α and LCN2 levels (r_s=0.55; P=0.011; n=20) was evident for AI. LCN2 blood levels correlated with AI disease severity (r_s=0.65; P=0.000, n=29), but not with disease duration, age, sex, BMI, or smoking habit. Detailed analyses revealed a link with the number of skin regions containing nodules and fistulae, but not scars.

Conclusions

LCN2 might serve as a blood biomarker for objective assessment of inflammatory activity in AI. Additionally, we suggest a self-amplification loop comprising TNF-α, neutrophilic granulocytes, and LCN2, that contributes to the recurrent skin neutrophil infiltration in AI, clinically evident as pus.

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