{
  "abstract": "Objective Delivery of a small for gestational age (SGA) infant is a common pregnancy complication among women with SLE. Although disease activity and autoantibodies such as anti-Smith and anti-ribonucleoprotein 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 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) 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 Discovery proteomics identified four proteins with increased abundance in SLE-SGA compared with 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 pre-eclampsia. Endostatin levels were consistently higher in SLE compared with controls across all trimesters (p≤0.0001). Endostatin, but not angiogenin, was enriched in placental blood.Conclusion Our study did not validate the differentially abundant proteins as markers for SLE-SGA but suggested a link between the antiangiogenic and proangiogenic proteins, endostatin and angiogenin, respectively, and pre-eclampsia in SLE. Given the consistent elevation of endostatin throughout pregnancy in SLE compared with controls, its potential effects on placental development in SLE warrant further investigation.",
  "authors": [
    {
      "affiliations": [
        "Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden"
      ],
      "name": "Agnes Torell"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden"
      ],
      "name": "Kerstin Andersson"
    },
    {
      "affiliations": [
        "Department of Medicine, Division of Rheumatology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Iva Gunnarsson"
    },
    {
      "affiliations": [
        "Department of Medicine, Division of Rheumatology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Elisabet Svenungsson"
    },
    {
      "affiliations": [
        "Department of Medicine, Division of Rheumatology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Agneta Zickert"
    },
    {
      "affiliations": [
        "Department of Women's and Children's Health, Division of NeonGynecology an Reproductive Health, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden"
      ],
      "name": "Maria Majczuk 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 A 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 Children's and Women’s 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 Ronnblom"
    },
    {
      "affiliations": [
        "Department of Women’s and Children’s Health, Section of Obstetrics and Gynecology, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Tansim Akhter"
    },
    {
      "affiliations": [
        "Department of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy at the 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": [
        "Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden"
      ],
      "name": "Anna Rudin"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden"
      ],
      "name": "Marit Stockfelt"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden"
      ],
      "name": "Anna-Carin Lundell"
    }
  ],
  "title": "Proteomic analysis reveals angiogenesis-related plasma proteins associated with pre-eclampsia in SLE",
  "uid": "39f31887-3b1b-5e8d-a941-ccd01058e902"
}