{
  "abstract": "Background Interstitial fibrosis in lupus nephritis (LN) is often infiltrated by immune cells but typically regarded as non-specific ‘scar reaction’. This study aimed to investigate the relationship between inflammatory fibrosis and kidney disease progression in LN.Methods Interstitial fibrosis and tubular atrophy (IFTA) were scored in 124 LN kidney biopsies. Inflammation in areas of IFTA (i-IFTA) was graded 0–3 according to the Banff Classification of Allograft Pathology. Significant glomerular filtration rate (GFR) loss was defined as a decline of >15 mL/min at 3 years from biopsy. Immune cell phenotype was defined by serial immunohistochemistry (13-plex).Results IFTA was observed in 88/124 (71%) biopsies, and i-IFTA was identified in 76/88 (86%) cases. The distribution of i-IFTA grades was heterogeneous across all IFTA grades. In patients with moderate-to-severe IFTA (>25%), the degree of i-IFTA was associated with a higher risk of significant GFR loss: 0/1 (0%), 0/3 (%), 3/4 (75%) and 7/9 (78%) for i-IFTA grades 0, 1, 2 and 3, respectively (p=0.015). Multiplexed histology revealed that i-IFTA was mostly composed of CD163+ macrophages and CD4 T cells, followed by CD8 T cells and granulocytes.Conclusion I-IFTA is frequently observed in LN and is dominated by macrophages and T cells. For patients with baseline IFTA >25%, the degree of i-IFTA emerged as a predictor of GFR loss. These data support the routine scoring of i-IFTA in LN due to its prognostic implications and nominate i-IFTA as a potential therapeutic target.",
  "authors": [
    {
      "affiliations": [
        "Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA",
        "Clinical and Research Laboratory on Urinary Sediment, UOC Nefrologia, Dialisi e Trapianto di Rene, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy"
      ],
      "name": "Silvia Malvica"
    },
    {
      "affiliations": [
        "Nephrology and Dialysis Unit, Azienda USL—IRCCS di Reggio Emilia, Reggio Emilia, Italy"
      ],
      "name": "Paride Fenaroli"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland, USA"
      ],
      "name": "Chen-Yu Lee"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland, USA"
      ],
      "name": "Sarah Louis"
    },
    {
      "affiliations": [
        "University of Rome La Sapienza, Rome, Italy"
      ],
      "name": "Alessandra Ida Celia"
    },
    {
      "affiliations": [
        "Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA"
      ],
      "name": "Serena Bagnasco"
    },
    {
      "affiliations": [
        "Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA"
      ],
      "name": "Xiaoping Yang"
    },
    {
      "affiliations": [
        "Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA"
      ],
      "name": "Daniel Salvetti"
    },
    {
      "affiliations": [
        "Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA"
      ],
      "name": "Jeffrey Hodgin"
    },
    {
      "affiliations": [
        "Rheumatology, NYU Grossman School of Medicine, New York City, New York, USA"
      ],
      "name": "H Michael Belmont"
    },
    {
      "affiliations": [
        "Rheumatology, NYU Grossman School of Medicine, New York City, New York, USA"
      ],
      "name": "Peter Izmirly"
    },
    {
      "affiliations": [
        "Rheumatology, NYU Grossman School of Medicine, New York City, New York, USA"
      ],
      "name": "Jill P Buyon"
    },
    {
      "affiliations": [
        "University of Maryland Medical Center, Baltimore, Maryland, USA"
      ],
      "name": "Laurence Magder"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland, USA"
      ],
      "name": "Michelle A Petri"
    },
    {
      "affiliations": [
        "Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA",
        "Clinical and Research Laboratory on Urinary Sediment, UOC Nefrologia, Dialisi e Trapianto di Rene, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy",
        "Nephrology and Dialysis Unit, Azienda USL—IRCCS di Reggio Emilia, Reggio Emilia, Italy",
        "Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland, USA",
        "University of Rome La Sapienza, Rome, Italy",
        "Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA",
        "Rheumatology, NYU Grossman School of Medicine, New York City, New York, USA",
        "University of Maryland Medical Center, Baltimore, Maryland, USA"
      ],
      "name": "The Accelerating Medicines Partnership: RA/SLE Network"
    },
    {
      "affiliations": [
        "Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA"
      ],
      "name": "Avi Rosenberg"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland, USA"
      ],
      "name": "Andrea Fava"
    }
  ],
  "title": "Inflammation in areas of fibrosis precedes loss of kidney function in lupus nephritis",
  "uid": "3b5887f8-71bf-5f16-b1df-c143836e0760"
}