IgA interaction with carboxy-terminal 43-kD fragment of fibronectin in IgA nephropathy.
IgA deposition in the glomerular mesangial matrix is a prerequisite for the diagnosis of IgA nephropathy, and circulating IgA-containing complex has been implicated in this process. Since fibronectin is known to be involved in the assembly of extracellular matrix, this study was conducted to investigate whether fibronectin and its fragments are present in sera of patients and are capable of binding IgA1. Sera from patients with IgA nephropathy were purified by heparin-affinity chromatography, and column eluate were analyzed for the presence of fibronectin using Western blot and a set of anti-fibronectin monoclonal antibodies. Native fibronectin was digested with cathepsin D to obtain fragments similar to those of serum fibronectin. The capacity of fibronectin to bind IgA was examined with a mixture of purified IgA1 and cathepsin D-digested fibronectin fragments. A 43-kD carboxy-terminal fragment of fibronectin was detected in samples derived from sera of patients with IgA nephropathy but not in healthy control subjects. A similar-sized fragment was generated by cathepsin D digestion of the native molecule and was shown to bind to IgA1 in vitro. Since the carboxy-terminal domain is known to be critical in assembling exogenous fibronectin into the extracellular matrix, the affinity to IgA1 to a fragment found in patients may have pathogenic potential to mediate extracellular IgA deposition in IgA nephropathy.
Waga
S
S
Department of Pediatrics, Hirosaki University School of Medicine, Aomori, Japan. SW2736@cc.hirosaki-u.ac.jp
Sugimoto
K
K
Tanaka
H
H
Ito
T
T
Nakahata
T
T
Tateyama
T
T
Kakizaki
Y
Y
Yokoyama
M
M
D002846:Chromatography, Affinity; D002847:Chromatography, Agarose; D005353:Fibronectins / Q000097:blood / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000097:blood*; D006493:Heparin; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000378:metabolism*; D037102:Lectins; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism*; D037121:Plant Lectins
D005353:Fibronectins; D007070:Immunoglobulin A; D037102:Lectins; D010446:Peptide Fragments; D037121:Plant Lectins; C043696:jacalin; D006493:Heparin