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SAT0187 The Antimicrobial Peptide LL-37 and Type I Interferon in Idiopathic Inflammatory Myopathies
  1. X. Lu1,
  2. Q. Tang2,
  3. E. Lindroos2,
  4. M. Lindh3,
  5. B. Agerberth3,
  6. I. Lundberg2,
  7. C. Wick2
  1. 1Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China
  2. 2Rheumatology Unit, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital
  3. 3Department of Laboratory Medicine, Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden

Abstract

Background The human antimicrobial peptide LL-37, exhibits a variety of biological functions such as activation of plasmacytoid dendritic cells (pDC) to produce type I interferon and mediate tissue damage. In autoimmune diseases such as systemic lupus erythematosus, rheumatic arthritis, and psoriasis LL-37 released by neutrophils is overexpressed at inflammatory sites and may have a role in pathogenesis by induction of type I interferon pathway. Type I interferon pathway is activated in subgroups of patients with idiopathic inflammatory myopathies (IIM). The mechanisms that drive type I interferon in IIM is unclear. We hypothesized that LL-37 in muscle and/or skin may be a factor that can activate type I interferon in these conditions.

Objectives The aim of our study was to investigate the expression of LL-37 and type I interferon related proteins (MxA) in the affected organs of patients with polymyositis (PM) and dermatomyositis (DM).

Methods Twelve muscle and 5 skin biopsies were obtained from 6 PM and 6 DM patients. Additional 3 skin biopsies taken from non-affected skin in 3 of DM patients. Five muscle and 7 skin biopsies from healthy subjects were selected as controls (HC). Immunohistochemistry staining of LL-37, CD66b (neutrophil), MxA (type I interferon), BDCA-2 (pDC), CD68 and CD163 (both macrophage markers) were performed in all muscle and skin specimens. Western blot (WB) was utilized to confirm the expression of LL-37 in muscle and skin tissues. Co-localization of LL-37 and neutrophils in muscle and skin tissue was confirmed by double-staining. The relationship of the markers were analyzed and compared with the clinical features of PM/DM patients.

Results The expression of LL-37, CD66b, BDCA-2, and MxA in muscle as well as in skin tissue was significantly higher in PM/DM patients when compared to HC (P<0.05). In addition, LL-37 expression in skin lesions of DM patients was higher than in non-affected skin from the same patient (P<0.05). WB confirmed LL-37 expression in muscle and skin tissues of PM/DM patients but was negative in HC. A positive correlation was found between expression of LL-37 and CD66b in muscle and skin tissues of PM/DM patients (R=0.89 and 0.69 respectively, P<0.05). Double-staining revealed co-localization of LL-37 and neutrophils in both muscle and skin tissues. The expression of CD66b correlated to MxA expression in muscle tissue in PM/DM patients (R=0.58, P<0.05). Expression of LL-37 and CD66b in muscle tissue correlated to serum CK levels (R=0.85 and 0.88 respectively, P<0.05). LL-37 and CD66b expression in skin tissue correlated with disease activity (physician global assessment score) in DM patients.

Conclusions The presence of the antimicrobial peptide LL-37 in affected muscle and skin tissues of patients with PM and DM together with the correlation of expression of LL-37 to the type I inducible protein MxA might indicate a role of LL-37 as an inducer of interferon production in patients with PM and DM. Thus, LL-37 may be involved in the pathogenesis of these diseases.

  1. Hoffmann MH, Bruns H, Bäckdahl L, et al. The cathelicidins LL-37 and rCRAMP are associated with pathogenic events of arthritis in humans and rats. Ann Rheum Dis. 2013 Jul;72(7):1239–48.

Disclosure of Interest None declared

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