{
  "abstract": "Objectives OBJECTIVE: Delivery of a small for gestational age (SGA) infant is a common pregnancy complication among women with systemic lupus erythematosus (SLE). Although disease activity and autoantibodies such as anti-Smith and anti-RNP associate with SGA, underlying pathological mechanisms remain unclear and reliable predictors are lacking. To address this, we applied a proteomic approach to identify proteins associated with SGA in SLE.Methods METHODS Plasma samples were collected repeatedly during pregnancy, at delivery, and from placental intervillous blood in women with SLE (n=83) and healthy controls (n=67) enrolled in the prospective SLE-Placenta study. Postpartum samples (6 months after delivery) from a subset of women with SLE (n=19) served as non-pregnant controls. Mass spectrometry was performed on a discovery cohort comprising six healthy uncomplicated pregnancies, eight uncomplicated SLE pregnancies, and eight SLE pregnancies complicated by SGA (SLE-SGA). Differential protein abundance analysis was performed in R. Candidate proteins were quantified by ELISA in the full cohort.Results RESULTS Discovery proteomics identified four proteins with increased abundance in SLE-SGA compared to uncomplicated SLE pregnancies: endostatin (Padj=0.0003), angiogenin (Padj=0.03), insulin-like growth factor-binding protein 5 (Padj=0.03) and complement factor H-related protein 5 (Padj=0.004). In the full cohort, ELISA quantification did not confirm increased levels of these proteins in SLE-SGA but suggested elevated levels of the angiogenesis-related proteins endostatin and angiogenin in women with SLE who later developed preeclampsia. Endostatin levels were consistently higher in SLE compared to controls across all trimesters (p=0.0001). Endostatin, but not angiogenin, was enriched in placental intervillous blood.Conclusions CONCLUSION Our study did not validate the differentially abundant proteins as markers for SLE-SGA but suggested a link between the anti- and pro-angiogenic proteins, endostatin and angiogenin, respectively, and preeclampsia in SLE. Given the consistent elevation of endostatin throughout pregnancy in SLE compared to controls, its potential effects on placental development in SLE warrant further investigation.",
  "authors": [
    {
      "affiliations": [
        "Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"
      ],
      "name": "Anna-Carin Lundell"
    },
    {
      "affiliations": [
        "Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"
      ],
      "name": "Agnes Torell"
    },
    {
      "affiliations": [
        "Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"
      ],
      "name": "Kerstin Andersson"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Iva Gunnarsson"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Elisabet Svenungsson"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Agneta Zickert"
    },
    {
      "affiliations": [
        "Departmen of Womens and Childens Health, division of NeonGynecology and Reproductive Health, Karolinska Hospital, Stockholm, Sweden"
      ],
      "name": "Maria Majcuk Sennström"
    },
    {
      "affiliations": [
        "Rheumatology, Sahlgrenska University Hospital, Gothenburg, Sweden"
      ],
      "name": "Estelle Trysberg"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences Lund, Rheumatology, Lund University, Skåne University Hospital, Lund, Sweden"
      ],
      "name": "Anders Bengtsson"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences Lund, Rheumatology, Lund University, Skåne University Hospital, Lund, Sweden"
      ],
      "name": "Andreas Jönsen"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences Lund, Obstetrics and Gynecology, Lund University, Skåne University Hospital, Lund, Sweden"
      ],
      "name": "Helena Strevens"
    },
    {
      "affiliations": [
        "Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden"
      ],
      "name": "Christopher Sjöwall"
    },
    {
      "affiliations": [
        "Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden"
      ],
      "name": "Muna Saleh"
    },
    {
      "affiliations": [
        "Department of Biomedical and Clinical Sciences, Division of Childrens and Womens Health, Linköping University, Linköping, Sweden"
      ],
      "name": "Sofia Pihl"
    },
    {
      "affiliations": [
        "Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Dag Leonard"
    },
    {
      "affiliations": [
        "Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Lars Rönnblom"
    },
    {
      "affiliations": [
        "Department of Womens and Childrens Health, Section of Obstetrics and Gynecology, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Tansim Akhter"
    },
    {
      "affiliations": [
        "Dept of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"
      ],
      "name": "Johan Bylund"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Gothenburg, Sweden",
        "Department of Obstetrics and Gynecology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden"
      ],
      "name": "Bo Jacobsson"
    },
    {
      "affiliations": [
        "Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"
      ],
      "name": "Anna Rudin"
    },
    {
      "affiliations": [
        "Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden",
        "Rheumatology, Sahlgrenska University Hospital, Gothenburg, Sweden"
      ],
      "name": "Marit Stockfelt"
    }
  ],
  "title": "PO:08:205 Proteomic analysis reveals angiogenesis-related plasma proteins associated with pregnancy in systemic lupus erythematosus",
  "uid": "af702e29-3762-5483-ace4-87a38040c9e8"
}