title: Immunoglobulin A nephropathy: a pathophysiology view.
abstract: OBJECTIVE
  IgA nephropathy is one of the leading causes of primary glomerulonephritis worldwide and an important etiology of renal disease in young adults. IgA nephropathy is considered an immune complex-mediated disease.
  
  
  METHODS
  This review article summarizes recent evidence on the pathophysiology of IgA nephropathy.
  
  
  RESULTS
  Current studies indicate an ordered sequence of multi-hits as fundamental to disease occurrence. Altered glycan structures in the hinge region of the heavy chains of IgA1 molecules act as auto-antigens, potentially triggering the production of glycan-specific autoantibodies. Recognition of novel epitopes by IgA and IgG antibodies leads to the formation of immune complexes galactose deficient-IgA1/anti-glycan IgG or IgA. Immune complexes of IgA combined with FcαRI/CD89 have also been implicated in disease exacerbation. These nephritogenic immune complexes are formed in the circulation and deposited in renal mesangium. Deposited immune complexes ultimately induce glomerular injury, through the release of pro-inflammatory cytokines, secretion of chemokines and the resultant migration of macrophages into the kidney. The TfR1/CD71 receptor has a pivotal role in mesangial cells. New signaling intracellular mechanisms have also been described.
  
  
  CONCLUSIONS
  The knowledge of the whole pathophysiology of this disease could provide the rational bases for developing novel approaches for diagnosis, for monitoring disease activity, and for disease-specific treatment.
authors.affiliation: Division of Nephrology, Clinics Hospital, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Rafaela Cabral Gonçalves
authors.initials: RC
authors.lastname: Fabiano
authors.affiliation: Unit of Pediatric Nephrology, Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Sérgio Veloso Brant
authors.initials: SV
authors.lastname: Pinheiro
authors.affiliation: Unit of Pediatric Nephrology, Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil. acssilva@hotmail.com.|Pediatric Branch, Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Avenida Alfredo Balena, 190, Room# 281, Belo Horizonte, MG, 30130-100, Brazil. acssilva@hotmail.com.
authors.forename: Ana Cristina
authors.identifier: http://orcid.org/0000-0001-9222-3882
authors.initials: AC
authors.lastname: Simões E Silva
mesh_terms: D000818:Animals; D005922:Glomerulonephritis, IGA / Q000235:genetics / Q000276:immunology; D006801:Humans
keywords: Anti-glycan antibodies; Galactose deficiency; Glomerulonephritis; IgA nephropathy; IgA1 glycosylation