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AB0100 Identification of the antimicrobial peptide LL-37 as a potential mediator of synovial inflammation in RA
  1. P. Neregård1,
  2. M. Engström1,
  3. M. Lindh2,
  4. B. Agerberth2,
  5. A.I. Catrina1
  1. 1Department of Medicine, Rheumatology Unit, Karolinska Institute, Karolinska University Hospital
  2. 2Department of Medical Biochemistry and Biophysics, Chemistry I, Karolinska Institute, Stockholm, Sweden

Abstract

Background LL-37, a member of the cathelicidin family of host defense peptides, has a broad range of antimicrobial and immunomodulatory effects that potentially can have an impact on the regulation of the adaptive immune system.

Objectives In this study we aimed to investigate a potential role for LL-37 in mediating chronic synovial inflammation.

Methods 49 patients meeting the 1987 American College of Rheumatology (ACR) criteria for RA were recruited for this study. We evaluated LL-37 by immunohistochemistry in synovial biopsy samples obtained before and after a mean of 8 weeks of treatment from 15 patients treated with adalimumab, 12 patients treated with etanercept and 11 patients treated with methotrexate, as well as from 11 patients prior to and 2 weeks after injection with intraarticular glucocorticoids. LL-37 was also evaluated in synovial biopsies obtained from 10 healthy volunteers. Microscopic results were analyzed by double-blind semi-quantitative analysis. Synovial localization of LL-37 was performed by double fluorescent stainings for LL-37 and cell surface markers. LL-37 was detected in synovial fluid by Western blots. Statistical analysis was performed using Wilcoxon test for paired comparisons and Man-Whitney test for comparisons of independent samples.

Results LL-37 was expressed in most of the RA synovial biopsies both in the lining and sublining layers and readily identified in the synovial fluid. Serial and double-fluorescent immunostaining for cell surface markers identifies granulocytes (CD66 positive cells) and macrophages (CD163 positive cells) as main cells expressing LL-37. Inflamed synovial tissue obtained from active arthritis prior to treatment expressed higher levels of LL-37 as compared to healthy individuals. Treatment with adalimumab, etanercept and intraarticular glucocorticoids but not methotrexate resulted in a significant down-modulation of LL-37 expression.

Conclusions Our results demonstrate presence of LL-37 in the context of chronic synovial inflammation and show specific regulation of this molecule by distinct anti-rheumatic agents. Further investigation to reveal the functional consequences of our findings on synovial antimicrobial and inflammatory activity is needed.

Disclosure of Interest None Declared

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