{
  "abstract": "Objectives To investigate the proteome of inflammatory foci in CLE, aiming to elucidate the pathological processes occurring at the site of tissue injury within the skin.Methods Skin biopsies from 5 patients with CLE, 4 healthy controls and 2 cases uninvolved skin of CLE patients were investigated (altogether controls). Inflammatory foci were excised using laser capture microdissection and analyzed by tandem mass-spectroscopy. Raw protein data was processed using R (version 4.0+) and DESeq2 package. Cluster analysis was performed using String-Db platform with integrated open AI (ChatGPT). We merged up-and downregulated proteins in search for the top aberrant clusters.Results Study detected 1385 proteins. Significant expression difference was observed in 297 proteins (adj.p<0.05). In CLE 134 proteins were up- and 113 downregulated. Seven clusters containing >2 proteins were identified. Cluster 1 included interferon type I/immune activation and nucleic acid sensing proteins, mediators of leukocyte activation, nucleic-acid metabolism and factors that might increase autoantigen exposure. Multiple stress-response proteins were upregulated; but superoxide dismutase SOD3 - a key protector against oxidative stress - was downregulated. We observed dysregulation in cytoskeleton dynamics and cell migration: proteins governing adhesion, epithelial junctions, and barrier stability were dysregulated. Cluster 2 showed increased expression of structural collagens, proteoglycans, elastic-fibre components, whereas laminins - core constituents of the basement membrane were reduced, indicating extracellular matrix reinforcement with concomitant basement-membrane weakening. Cluster 3 suggested shift in ribosome composition: multiple large subunit ribosomal proteins were abundant, while only one small subunit protein was identified (RPS27) suggesting an imbalanced ribosomal signature and possible translational reprogramming. Cluster 4 included proteins in endoplasmic-reticulum-phagosome pathway, antigen recognition, processing and presentation. Cluster 5 showed downregulation of multiple proteins in histidine metabolism. Cluster 6 included multiple upregulated proteins important for mRNA 3-end processing, pre-mRNA splicing, spliceosome components and regulators, while LSM8, involved in pre-mRNA splicing, was single downregulated. Cluster 7 showed upregulated histone proteins, but MRE11 and PHGDH, important in double-stranded DNA repair were downregulated.Conclusions Integrated analysis of protein expression in CLE inflammatory foci uncovers dysregulation of multiple pathways and offers critical insights in local aberrant biological mechanisms.",
  "authors": [
    {
      "affiliations": [
        "Center for Rheumatology, Academic Specialist Centre and Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Vilija Oke"
    },
    {
      "affiliations": [
        "Section of Dermatology, Medicine Unit Dermatology, Gastroenterology, Rheumatology",
        "Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Karin Popovic"
    },
    {
      "affiliations": [
        "Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery, New York, USA"
      ],
      "name": "Timothy B Niewold"
    },
    {
      "affiliations": [
        "Department of Dermatology, Mayo Clinic, Rochester, USA"
      ],
      "name": "Alexander Meves"
    },
    {
      "affiliations": [
        "Department of Dermatology, Mayo Clinic, Rochester, USA"
      ],
      "name": "Julia Lehman"
    },
    {
      "affiliations": [
        "National Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory and Department of Immunotechnology, L, Lund, Sweden"
      ],
      "name": "Yuan Li"
    },
    {
      "affiliations": [
        "Mayo Clinic Medical Genome Facility, Proteomics Core, Rochester, USA"
      ],
      "name": "Cristine M Charlesworth"
    },
    {
      "affiliations": [
        "Mayo Clinic Medical Genome Facility, Proteomics Core, Rochester, USA"
      ],
      "name": "Benjamin Madden"
    },
    {
      "affiliations": [
        "Section of Rheumatology, Medicine Unit Dermatology, Rheumatology, Gastroenterology",
        "Karolinska University Hospital, Stockholm, USA"
      ],
      "name": "Elisabet Svenungsson"
    }
  ],
  "title": "PO:06:161 Cutaneous lupus erythematosus (CLE): proteomic profiling of inflammatory foci uncovers major aberrant pathways",
  "uid": "68b5086a-1150-51cc-a851-2bafb6260780"
}