{
  "abstract": "Objective SLE is a systemic autoimmune disease in which the complement system plays a key pathogenic role, yet the contribution of the lectin pathway remains unclear. Lectin pathway-dependent complement activation is initiated by pattern-recognition molecules complexed with mannose-binding lectin (MBL)-associated serine proteases (MASPs) and MBL-associated proteins (MAPs). Here, we combined biochemical and genetic analyses to explore associations between MASP/MAP proteins, SLE manifestations and autoantibody specificities.Methods Serum concentrations of MASP-3, MAP-1 and MASP-2 were measured using ELISA in Swedish patients with SLE (n=522) and population-based matched controls (n=322). Serum type I interferon activity was measured by a cell-based reporter assay. Associations with SLE manifestations and autoantibodies were explored using logistic regression models. Single-nucleotide genetic variants spanning the MASP1 and MASP2 genes were analysed for associations with MASP/MAP levels and SLE manifestations.Results Patients with MAP-1 serum concentrations in the highest quartile had significantly higher rates of discoid rash (OR 2.8 (95% CI 1.4 to 5.7)), haematological manifestations (OR 2.1 (95% CI 1.1 to 3.7)) and autoantibodies against Sm, RNP, SSA and SSB (ORs 2.4 (95% CI 1.3 to 4.6) to 3.6 (95% CI 1.7 to 7.7)). Patients in the highest quartiles of MAP-1 and MASP-2 had lower rates of anti-β2GP1 and anti-cardiolipin IgG and IgA anti-phospholipid antibodies (ORs 0.29 (95% CI 0.12 to 0.68) to 0.56 (95% CI 0.31 to 1.0)). Serum MAP-1 levels correlated with type I interferon activity (Spearman’s rho 0.34, p<0.0001), which mediated the associations of MAP-1 with haematological manifestations and Sm/RNP autoantibodies. Significant protein quantitative trait loci for MAP-1 and MASP-2 were identified; however, these did not show consistent associations with SLE or specific SLE manifestations.Conclusions These results demonstrate a distinct clinical and serological SLE profile associated with components of the lectin pathway. The lectin pathway-regulatory protein MAP-1 displayed the strongest associations and may serve as a marker of SLE manifestations with a type I interferon signature.",
  "authors": [
    {
      "affiliations": [
        "Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Linnea Lindelöf"
    },
    {
      "affiliations": [
        "Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark"
      ],
      "name": "Peter Garred"
    },
    {
      "affiliations": [
        "National Bioinformatics Infrastructure Sweden, Department of Biochemistry and Biophysics, Stockholm University, Science for Life Laboratory, Stockholm, Sweden"
      ],
      "name": "Mun-Gwan Hong"
    },
    {
      "affiliations": [
        "Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark"
      ],
      "name": "Sasha Wahl Vælum"
    },
    {
      "affiliations": [
        "Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark"
      ],
      "name": "Lotte Holten Petersen"
    },
    {
      "affiliations": [
        "Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Dag Leonard"
    },
    {
      "affiliations": [
        "Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Ahmed Sayadi"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden",
        "Academic Specialist Center, Center for Rheumatology, Stockholm, Sweden"
      ],
      "name": "Vilija Oke"
    },
    {
      "affiliations": [
        "Barbara Volcker Center for Women and Rheumatic Diseases, Hospital for Special Surgery, New York City, New York, USA"
      ],
      "name": "Timothy B Niewold"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Lina-Marcela Diaz-Gallo"
    },
    {
      "affiliations": [
        "Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland",
        "Department of Medicine, Karolinska Institute Clinical Epidemiology Division, Stockholm, Sweden"
      ],
      "name": "Saedis Saevarsdottir"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Iva Gunnarsson"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Elisabet Svenungsson"
    },
    {
      "affiliations": [
        "Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Oskar Eriksson"
    }
  ],
  "title": "Lectin pathway of complement in SLE: MAP-1 as a marker of haematological manifestations and elevated type I interferon activity",
  "uid": "326c4692-69a4-574f-a0cf-f7e6ada017c2"
}