Proteome study of cutaneous lupus erythematosus (CLE) and dermatomyositis skin lesions reveals IL-16 is differentially upregulated in CLE

Timothy B. Niewold1, Alexander Meves2, Julia S. Lehman3,2, Karin Popovic-Silwerfeldt4, Aliisa Häyry5, Therese Söderlund-Matell5,6, Cristine M. Charlesworth7, Benjamin Madden7, Ingrid E. Lundberg5,6, Marie Wahren-Herlenius5, Elisabet Svenungsson5,6, Vilija Oke8,5
1Colton Center for Autoimmunity, New York University School of Medicine, New York, USA
2Department of Dermatology, Mayo Clinic, Rochester, USA
3Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, USA
4Dermatology Clinic, Department of Clinical Sciences at Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
5Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Rheumatology, Karolinska University Hospital, Stockholm, Sweden
7Mayo Clinic Medical Genome Facility - Proteomics Core, Rochester, USA
8Center for Rheumatology, Academic Specialist Center, Stockholm Healthcare Services, Stockholm, Sweden

Tóm tắt

The objective of the study was to explore the disease pathways activated in the inflammatory foci of skin lesions in cutaneous lupus erythematosus (CLE) and dermatomyositis (DM). Skin biopsies acquired from active CLE and DM lesions, patient (PC), and also healthy controls (HC) were investigated. Biopsy sections were examined by a pathologist, inflammatory foci were laser micro-dissected and captured, and proteins within captured tissue were detected in an unbiased manner by mass spectrometry. Protein pathway analysis was performed by the string-db.org platform. Findings of interest were confirmed by immunohistochemistry (IHC). Proteome investigation identified abundant expression of interferon-regulated proteins (IRP) as a common feature of CLE and DM. Interleukin (IL)-16 was the only abundant cytokine differentially expressed in CLE compared to DM. Caspase-3, an enzyme that cleaves IL-16 into its active form, was detected in low levels. Significantly higher proportion of IL-16- and caspase-3-positive cells was identified in CLE lesions in comparison with DM, PC, and HC. Proteomic results indicate more abundant complement deposition in CLE skin lesions. Using unbiased mass spectrometry investigation of CLE and DM inflammatory infiltrates, we confirmed that high IRP expression is a common feature of both CLE and DM, while IL-16 is the only differentially expressed cytokine in CLE. IHC confirmed high expression of IL-16 and caspase-3 in CLE. Our novel molecular findings indicate that IL-16 detection could be useful in differential diagnostics between the two conditions that can display similar histopathological appearance. IL-16 could be of interest as a future therapeutic target for CLE.

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