No evidence of pathogenic involvement of cathelicidins in patient cohorts and mouse models of lupus and arthritis

Kienhofer D, Hahn J, Schubert I, Reinwald C, Ipseiz N, Lang S, Borras EB, Amann KU, Sjowall C, Barron AE, Hueber A, Agerberth B, Schett G, Hoffmann M (2014)

Publication Type: Journal article

Publication year: 2014

Journal

PLoS ONE Public Library of Science

Book Volume: 9

Pages Range: e115474

Journal Issue: 12

DOI: 10.1371/journal.pone.0115474

Abstract

Apart from their role in the immune defence against pathogens evidence of a role of antimicrobial peptides (AMPs) in autoimmune diseases has accumulated in the past years. The aim of this project was to examine the functional impact of the human cathelicidin LL-37 and the mouse cathelicidin-related AMP (CRAMP) on the pathogenesis of lupus and arthritis. Serum LL-37 and anti-LL-37 levels were measured by ELISA in healthy donors and patients with Systemic Lupus Erythematosus (SLE) and Rheumatoid arthritis (RA). Pristane-induced lupus was induced in female wild type (WT) and cathelicidin-deficient (CRAMP-/-) mice. Serum levels of anti-Sm/RNP, anti-dsDNA, and anti-histone were determined via ELISA, cytokines in sera and peritoneal lavages were measured via Multiplex. Expression of Interferon I stimulated genes (ISG) was determined by real-time PCR. Collagen-induced arthritis (CIA) was induced in male WT and CRAMP-/- mice and arthritis severity was visually scored and analysed histomorphometrically by OsteoMeasure software. Serum levels of anti-LL-37 were higher in SLE-patients compared to healthy donors or patients with RA. However, no correlation to markers of disease activity or organ involvement was observed. No significant differences of autoantibody or cytokine/chemokine levels, or of expression of ISGs were observed between WT and CRAMP-/- mice after pristane-injection. Furthermore, lung and kidney pathology did not differ in the absence of CRAMP. Incidence and severity of CIA and histological parameters (inflammation, cartilage degradation, and bone erosion) were not different in WT and CRAMP-/- mice. Although cathelicidins are upregulated in mouse models of lupus and arthritis, cathelicidin-deficiency did not persistently affect the diseases. Also in patients with SLE, autoantibodies against cathelicidins did not correlate with disease manifestation. Reactivity against cathelicidins in lupus and arthritis could thus be an epiphenomenon caused by extensive overexpression in blood and affected tissues. In addition, other cationic AMPs could functionally compensate for the deficiency of cathelicidins.

Authors with CRIS profile

Jonas Hahn Department of Medicine 3 – Rheumatology and Immunology Christiane Reinwald Department of Medicine 3 – Rheumatology and Immunology Kerstin Ute Amann Department of Nephropathology Axel Hueber Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III Markus Hoffmann Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Karolinska Institute SE Sweden (SE) Stanford University US United States (USA) (US) Linköping University SE Sweden (SE) Autonomous University of Barcelona (UAB) / Universitat Autònoma de Barcelona ES Spain (ES)

How to cite

APA:

Kienhofer, D., Hahn, J., Schubert, I., Reinwald, C., Ipseiz, N., Lang, S.,... Hoffmann, M. (2014). No evidence of pathogenic involvement of cathelicidins in patient cohorts and mouse models of lupus and arthritis. PLoS ONE, 9(12), e115474. https://doi.org/10.1371/journal.pone.0115474

MLA:

Kienhofer, D., et al. "No evidence of pathogenic involvement of cathelicidins in patient cohorts and mouse models of lupus and arthritis." PLoS ONE 9.12 (2014): e115474.

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