title: Mesangial cells from patients with IgA nephropathy have increased susceptibility to galactose-deficient IgA1.
abstract: BACKGROUND
  IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, affecting close to a million people. Circulating galactose-deficient IgA (gd-IgA), present in patients with IgAN, form immune complex deposits in the glomerular mesangium causing local proliferation and matrix expansion. Intriguing though, individuals having gd-IgA deposits in the kidneys do not necessarily have signs of glomerular disease. Recurrence of IgAN only occurs in less than half of transplanted patients with IgAN, indicating that gd-IgA is not the only factor driving the disease. We hypothesize that, in addition to IgA complexes, patients with IgAN possess a subtype of mesangial cells highly susceptible to gd-IgA induced cell proliferation.
  
  
  METHODS
  To test the hypothesis, we designed a technique to culture primary mesangial cells from renal biopsies obtained from IgAN patients and controls. The cell response to gd-IgA treatment was then measured both on gene and protein level and the proliferation rate of the cells in response to PDGF was investigated.
  
  
  RESULTS
  When treated with gd-IgA, mesangial cells from patients with IgAN express and release more PDGF compared to controls. In addition, the mesangial cells from patients with IgAN were more responsive to treatment with PDGF resulting in an increased proliferation rate of the cells compared to control. Mesangial cells cultured from patients with IgAN expressed and released more IL-6 than controls and had a higher expression of matrix genes. Both mesangial cells derived from patients with IgAN and controls increased their expressed TGFβ1 and CCL5 when treated with gd-IgA.
  
  
  CONCLUSIONS
  We conclude that mesangial cells derived from IgAN patients have a mesangioproliferative phenotype with increased reactivity to IgA and that these cellular intrinsic properties may be important for the development of IgA nephropathy.
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. kerstin.ebefors@neuro.gu.se.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Ebefors
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Peidi
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Emelie
authors.initials: E
authors.lastname: Lassén
authors.affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Johannes
authors.initials: J
authors.lastname: Elvin
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Candemark
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Clinical Sciences, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Levan
authors.affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Börje
authors.initials: B
authors.lastname: Haraldsson
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Nyström
mesh_terms: D000328:Adult; D000368:Aged; D000936:Antigen-Antibody Complex / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000187:drug effects / Q000276:immunology; D005260:Female; D005690:Galactose / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects* / Q000276:immunology; D010641:Phenotype; D053773:Transforming Growth Factor beta1 / Q000187:drug effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000936:Antigen-Antibody Complex; C483024:CCL5 protein, human; D018946:Chemokine CCL5; C508600:IL6 protein, human; D007070:Immunoglobulin A; D007155:Immunologic Factors; D015850:Interleukin-6; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D005690:Galactose
keywords: IgA nephropathy; Mesangial cells; PDGF