Pathogenesis of IgA nephropathy.
Immunoglobulin A (IgA) nephropathy is an immune-complex-mediated glomerulonephritis characterized by the presence of immunoglobulin A deposits in mesangial and paramesangial regions. The patients with IgA nephropathy present with varying clinical symptoms (eg, microhematuria with preserved renal function or progressive deterioration of renal functions resulting in end-stage renal disease). The factors involved in the pathogenetic mechanisms of IgA nephropathy include (1). environmental factors, (2). genetic factors, (3). abnormality of the IgA1 molecule, and (4). various inflammatory mediators. The gene polymorphism studies for human leukocyte antigen (HLA), renin-angiotensin-aldosterone system, and selectin gene clusters, suggest a certain degree of genetic predisposition in patients for IgA nephropathy. Also, the genome-wide screening in familial IgA nephropathy showed linkage of IgA nephropathy to the 6q22-23 chromosome. Besides genetic influence in its pathogenesis, aberrant galactosylation in serum IgA and IgA1 eluted from kidneys with IgA nephropathy has been observed, and conceivably such abnormalities induce the expression of various cytokines, interleukin (IL)-6, platelet-derived growth factor (PDGF), tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-beta1 in the renal cells, which contributes to further glomerular injury. Despite an enormous amount of information available in the literature, further studies are needed to delineate the precise pathogenetic mechanisms involved in primary IgA nephropathy and also to facilitate the development of newer therapeutic interventions.
Wada
Jun
J
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan. junwada@md.okayama-u.ac.jp
Sugiyama
Hitoshi
H
Makino
Hirofumi
H
D000818:Animals; D001707:Biopsy, Needle; D016207:Cytokines / Q000378:metabolism*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology; D012307:Risk Factors; D012680:Sensitivity and Specificity
D016207:Cytokines; D005819:Genetic Markers