Expression of Anti-Microbial Peptide LL-37 Correlates to the Activation of Type I Interferon Pathway in Patients with Idiopathic Inflammatory Myopathies

Xin Lu¹, Quan Tang², Monica Lindh³, Birgitta Agerberth⁴, Maryam Dastmalchi⁵, Ingrid E. Lundberg⁶ and Cecilia Wick⁷, ¹Rheumatology, China-Japan Friendship Hospital, Beijing, China, ²Department of Medicine, Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden, ³Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden, ⁴Department of Medical Biochemistry and Biophysics, Chemistry I, Karolinska Institute, Stockholm, Sweden, Stockholm, Sweden, ⁵Unit of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden, ⁶Department of Medicine, Rheumatology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden, ⁷Rheumatology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Idiopathic Inflammatory Myopathies (IIM)

Session Information

Date: Sunday, November 13, 2016

Title: Muscle Biology, Myositis and Myopathies - Poster I: Basic/Translational

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Polymyositis (PM) and dermatomyositis (DM) are systemic autoimmune diseases whose pathogenesis remain unclear. The type I interferon system has recently been suggested to have a role in subgroups of myositis patients, however the triggering factor have not yet been clarified. The anti-microbial peptide, LL-37, carriers numerous immunomodulatory properties in addition to its anti-microbial activity and is implicated in the pathogenesis of several autoimmune diseases through activation of the type I interferon pathway. The aim of this study was to explore a potential role of LL-37 in the pathogenesis of PM and DM.

Methods: Muscle biopsies taken from 6 PM, 6 DM and 5 healthy controls(HC) and skin biopsies taken from both affected (5 DM) and non-affected(3 of DM) areas and 6 HC were immunohistochemically stained for LL-37(monoclonal and polyclonal), CD66b(neutrophil), MxA(type I interferon induced protein) and BDCA-2(pDC). Double immunofluorescence stainings for LL-37 and CD66b was performed. The expression of LL-37 in muscle was confirmed with western blot.

Results: The expression of LL-37 was significantly increased in muscle tissue and symptomatic skin in patients with PM/DM compared to that in HC. LL-37 was mainly expressed by neutrophils as confirmed with double staining. The expression of monoclonal LL-37 positively correlated to CD66b expression in both muscle and skin tissues in PM/DM patients(R=0.9 and 0.74 respectively, P<0.01). BDCA-2 positive pDCs was significantly increased in muscle tissue in patients when compared to HC. MxA was expressed in the same areas as LL-37, CD66b and BDCA-2, and positively correlated with CD66b expression in muscle tissue in all patients(R=0.59, P<0.05). Moreover, the muscular expression of LL-37 and CD66b correlated with increased serum creatine kinase levels(R=0.62 and 0.71 respectively, P<0.05). Monoclonal LL-37 expression in muscle tissue in patients with short disease duration correlated negatively to FI-2 score (P<0.05, R=0.77).

Conclusion: The data indicated that neutrophil-derived LL-37 may induce type I interferon production in affected muscle and skin tissues in patients with PM and DM and be involved in the pathogenesis of these conditions.

Disclosure: X. Lu, Project grants from Astra-Zeneca, Bristol Myers Squibb Scientific advisor: Bristol Myers Squibb, Idera and aTyr., 2; Q. Tang, Project grants from Astra-Zeneca, Bristol Myers Squibb Scientific advisor: Bristol Myers Squibb, Idera and aTyr., 2; M. Lindh, Project grants from Astra-Zeneca, Bristol Myers Squibb Scientific advisor: Bristol Myers Squibb, Idera and aTyr., 2; B. Agerberth, Project grants from Astra-Zeneca, Bristol Myers Squibb Scientific advisor: Bristol Myers Squibb, Idera and aTyr., 2; M. Dastmalchi, Project grants from Astra-Zeneca, Bristol Myers Squibb Scientific advisor: Bristol Myers Squibb, Idera and aTyr., 2; I. E. Lundberg, Project grants from Astra-Zeneca, Bristol Myers Squibb Scientific advisor: Bristol Myers Squibb, Idera and aTyr., 2; C. Wick, Project grants from Astra-Zeneca, Bristol Myers Squibb Scientific advisor: Bristol Myers Squibb, Idera and aTyr., 2.

To cite this abstract in AMA style:

Lu X, Tang Q, Lindh M, Agerberth B, Dastmalchi M, Lundberg IE, Wick C. Expression of Anti-Microbial Peptide LL-37 Correlates to the Activation of Type I Interferon Pathway in Patients with Idiopathic Inflammatory Myopathies [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/expression-of-anti-microbial-peptide-ll-37-correlates-to-the-activation-of-type-i-interferon-pathway-in-patients-with-idiopathic-inflammatory-myopathies/. Accessed .

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