title: Pathophysiology of IgA Nephropathy.
abstract: Immunoglobulin (Ig)A nephropathy is the most prevalent primary chronic glomerular disease in the world. Studies of molecular and cellular interactions involved in the pathogenesis of IgA nephropathy have revealed several inherent abnormalities in the production and subsequent handling of IgA1. In patients with this disease, altered glycan structures in the unique hinge region of the heavy chains of IgA1 molecules lead to the exposure of antigenic determinants, which are recognized by naturally occurring antiglycan antibodies of the IgG and/or IgA1 isotype. In addition, due to a homing abnormality there is a gradual shift of mucosal IgA1 producing lymphoplasma cells from mucosal lymphoid tissue to bone marrow resulting in excess production of mucosal-type IgA1 in the systemic circulation. As a result, nephritogenic immune complexes form in the circulation and deposit in the glomerular mesangium. Deposited immune complexes induce proliferation of resident mesangial cells with increased production of extracellular matrix proteins. A number of inflammatory cytokines produced by the mesangial cells damage the filtration barrier resulting in hematuria and proteinuria ultimately leading to progressive renal damage.
authors.affiliation: Departments of *Pathology and Laboratory Medicine †Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Turki
authors.initials: T
authors.lastname: Al Hussain
authors.forename: Maged H
authors.initials: MH
authors.lastname: Hussein
authors.forename: Hadeel
authors.initials: H
authors.lastname: Al Mana
authors.forename: Mohammed
authors.initials: M
authors.lastname: Akhtar
mesh_terms: D005922:Glomerulonephritis, IGA / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans