ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1098

Comparative Analysis of the Total Proteome of the Skin Lesions from Cutaneous Lupus Erythematosus (CLE) and Dermatomyositis (DM)

Timothy B. Niewold1, Alexander Meves2, Julia S. Lehman3, Karin Popovic-Silwerfeldt4, Cristine Charlesworth5, Marie Wahren-Herlenius6, Elisabet Svenungsson7 and Vilija Oke8, 1Colton Center for Autoimmunity, New York University, New York, NY, 2Cancer Cenetr, Dermatology, Mayo Clinic, Rochester, MN, 3Pathology and Dermatology, Mayo Clinic College of Medicine and Science, Rochester, MN, MN, 4Department of Clinical Sciences, Dermatology Clinic, Danderyds Hospital,, Stockholm, Sweden, 5Mayo Clinic, Rochester, MN, 6Unit of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden, 7Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, Stockholm, Sweden, 8Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Date: Monday, October 22, 2018

Title: Systemic Lupus Erythematosus – Etiology and Pathogenesis Poster II

Session Type: ACR Poster Session B

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

Background/Purpose:

Cutaneous lupus erythematosus (CLE) and dermatomyositis (DM) are autoimmune diseases. The histopathological pattern of skin involvement can be similar, i.e. interface dermatitis, but the systemic manifestations are very different. While dermatomyositis commonly affect muscles, lupus erythematosus may affect any organ system. Autoantibodies against intracellular targets are common in both conditions, but the specific targets of the autoantibodies differ between the two conditions.

Our aim was to investigate a whole proteome of inflammatory foci of the CLE and DM lesions in a comparator manner and identify disease unique mechanisms of inflammation.

Methods: Patients with CLE (n=6), DM (n=5) and controls (n=6) were included and biopsied at diagnosis or disease exacerbation. Skin biopsies were examined by a pathologist, and selected inflammatory foci were laser microdissected. The total protein content of the microdissected tissue was then analyzed using mass-spectrometry.

Results:

In DM, there were 25 highly upregulated proteins, while CLE infiltrates were more protein rich and there were 88 proteins with up to 9-fold upregulation. Protein expression comparison between CLE and DM identified 22 differentially upregulated proteins, and all had higher abundance in CLE than in DM. A protein network analysis was performed by STRING platform (string-db.org). The network of interferon (IFN)-regulated proteins was abundant in both CLE and DM, including: IFIT, MX, OAS, STAT gene families and also EIF2AK2. Also, proteins involved in oxidative stress and antigen processing: IL4I1, TAP1 and TAP2 were highly upregulated in both CLE and DM. Proteins expressed differentially in CLE covered complement proteins (C1b), including membrane attack complex (C5, C6, C7, C8A and B) and complement regulators (CFHR1, CFHR2, CFHR5). Also, regulators of coagulation: thrombospondin 2 (THBS2), thrombin (F2) and annexin A3 (ANXA3) were highly abundant in CLE.

Conclusion: Inflammatory foci in the interface dermatitis in CLE and DM contain high abundance of IFN-regulated proteins, as well as regulators of oxidative stress and antigen processing. The proteomics technique allowed identification of pathways differentially activated in CLE, including complement activation products and regulators of coagulation. Our study identified multiple pathways activated at the site of inflammation which will be of interest in further search of new therapeutic targets.

Disclosure: T. B. Niewold, EMD Serono, 2; A. Meves, None; J. S. Lehman, None; K. Popovic-Silwerfeldt, None; C. Charlesworth, None; M. Wahren-Herlenius, None; E. Svenungsson, None; V. Oke, None.

To cite this abstract in AMA style:

Niewold TB, Meves A, Lehman JS, Popovic-Silwerfeldt K, Charlesworth C, Wahren-Herlenius M, Svenungsson E, Oke V. Comparative Analysis of the Total Proteome of the Skin Lesions from Cutaneous Lupus Erythematosus (CLE) and Dermatomyositis (DM) [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/comparative-analysis-of-the-total-proteome-of-the-skin-lesions-from-cutaneous-lupus-erythematosus-cle-and-dermatomyositis-dm/. Accessed .

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