title: New Insights into the Pathogenesis of IgA Nephropathy.
abstract: BACKGROUND
  IgA nephropathy, a frequent cause of end-stage renal disease, is an autoimmune disease wherein immune complexes consisting of IgA1 with galactose-deficientO-glycans (autoantigen) and anti-glycan autoantibodies deposit in glomeruli and induce renal injury. Multiple genetic loci associated with disease risk have been identified. The prevalence of risk alleles varies geographically, highest in eastern Asia and northern Europe, fewer in other parts of Europe and North America, and the least in Africa. IgA nephropathy is diagnosed from pathological assessment of a renal biopsy specimen. Currently, therapy is not disease-targeted but rather is focused on maintaining control of blood pressure and proteinuria, ideally with suppression of angiotensin II. Possible additional approaches differ between countries. Disease-specific therapy as well as new tools for diagnosis, prognosis, and assessment of responses to therapy are needed.
  
  
  CONCLUSIONS
  Glycosylation pathways associated with aberrantO-glycosylation of IgA1 and, thus, production of autoantigen, have been identified. Furthermore, unique characteristics of the autoantibodies in IgA nephropathy have been uncovered. Many of these biochemical features are shared by patients with IgA nephropathy and Henoch-Schönlein purpura nephritis, suggesting that the two diseases may represent opposite ends of a spectrum of a disease process. Understanding the molecular mechanisms involved in formation of pathogenic IgA1-containing immune complexes will enable development of disease-specific therapies as well as diagnostic and prognostic biomarkers.
  
  
  CONCLUSIONS
  IgA nephropathy is an autoimmune disease caused by glomerular deposition of nephritogenic circulating immune complexes consisting of galactose-deficient IgA1 (autoantigen) bound by anti-glycan autoantibodies. A better understanding of the multi-step process of pathogenesis of IgA nephropathy and the genetic and environmental contributing factors will lead to development of biomarkers to identify patients with progressive disease who would benefit from a future disease-specific therapy.
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Novak
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Rizk
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA ; School of Medicine, Fujita Health University, Toyoake, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA ; Longhua Hospital, Shanghai University of TCM, Shanghai, China.
authors.forename: XianWen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA ; Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Bian
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Hirouki
authors.initials: H
authors.lastname: Ueda
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Reily
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA ; Fudan University Huashan Hospital, Shanghai, China.
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Lai
authors.affiliation: Fudan University Huashan Hospital, Shanghai, China.
authors.forename: Chuanming
authors.initials: C
authors.lastname: Hao
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Lea
authors.initials: L
authors.lastname: Novak
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Huang
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Renfrow
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA ; Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Julian
keywords: Autoantibodies; IgA nephropathy; O-glycans; galactose deficiency; immune complexes