title: New developments in the genetics, pathogenesis, and therapy of IgA nephropathy.
abstract: Recent years have brought notable progress in the field of IgA nephropathy. Here, we highlight important new directions and latest developments, including successful discovery of several genetic susceptibility loci, formulation of the multihit pathogenesis model, introduction of the Oxford pathology scoring system, and formalization of the Kidney Disease Improving Global Outcomes (KDIGO) consensus treatment guidelines. We focus on the latest genetic findings that confirm a strong contribution of inherited factors and explain some of the geoethnic disparities in disease susceptibility. Most IgA nephropathy susceptibility loci discovered to date encode genes involved in the maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The concerted pattern of interpopulation allelic differentiation across all genetic loci parallels the disease prevalence and correlates with variation in local pathogens, suggesting that multilocus adaptation might have shaped the present-day landscape of IgA nephropathy. Importantly, the 'Intestinal Immune Network for IgA Production' emerged as one of the new targets for potential therapeutic intervention. We place these findings in the context of the multihit pathogenesis model and existing knowledge of IgA immunobiology. Lastly, we provide our perspective on the existing treatment options, discuss areas of clinical uncertainty, and outline ongoing clinical trials and translational studies.
authors.affiliation: Department of Medicine, Division of Nephrology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.|Division of Nephrology Dialysis and Transplantation, Department of Surgery, Medicine, Dentistry, Morphologic Science, Transplantation, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Magistroni
authors.affiliation: Division of Renal Pathology, Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: Vivette D
authors.initials: VD
authors.lastname: D'Agati
authors.affiliation: Department of Medicine, Division of Nephrology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Appel
authors.affiliation: Department of Medicine, Division of Nephrology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kiryluk
mesh_terms: D000116:Acetylgalactosamine / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D005922:Glomerulonephritis, IGA / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000276:immunology / Q000628:therapy; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics* / Q000378:metabolism*; D011379:Prognosis
chemical_list: D007070:Immunoglobulin A; D003165:Complement System Proteins; D000116:Acetylgalactosamine