Size-dependent binding of IgA to HepG2, U937, and human mesangial cells.
IgA nephropathy (IgAN) is characterized by increased circulating IgA and mesangial IgA deposition. The mechanism of mesangial IgA deposition remains poorly understood in IgAN. In this report, we studied the binding characteristics of serum IgA from patients with IgAN and healthy controls to different cell types, including a liver-cell line (HepG2), a monocytic cell line (U937), and human mesangial cells (HMCs). Jacalin-bound proteins (JBPs) were purified from serum IgA by means of jacalin affinity chromatography. Total IgA concentrations were significantly higher in patients with IgAN than in controls (P <.001). JBPs were further separated by means of size exclusion chromatography, and six pooled fractions with molecular weight ranging from 50 to 1,000 kD were obtained. The concentration of low-molecular-weight (LMW) IgA complexes (150-300 kD) and high-molecular-weight (HMW) IgA complexes (300-1,000 kD) were significantly higher in patients than in healthy controls (P <.001 and.05, respectively). Cultured human mesangial cells bound more IgA of 300 to 610 kD in IgA isolated from patients with IgAN (P <.01). The binding of IgA (LMW and HMW) from patients with IgAN to HepG2 was significantly higher than that of IgA preparations from controls. U937 significantly bound more IgA of 150 to 825 kD in IgA isolated from patients with IgAN (P <.01). Different and distinct binding patterns were observed in the three cell types for IgA with different molecular weights. HMCs bound more HMW than LMW IgA. We noted preferential binding of LMW (150 to 300 kDa) and intermediate (350-710 kDa) IgA to HepG2 than of IgA complexes of more than 710 kDa. U937 mainly bound LMW and intermediate size IgA (150 to 710 kDa) with no binding of IgA with size greater than 710 kD. Our findings suggest that monocytes, hepatocytes, and mesangial cells have unique properties with regard to their binding to different forms of IgA. These characteristic properties may alter the catabolism of circulating IgA and, hence, predispose their deposition in the kidney mesangium in IgAN.
Leung
Joseph C K
JC
Division of Nephrology, Department of Medicine, Queen Mary Hospital, University of Hong Kong.
Tsang
Anita W L
AW
Chan
Loretta Y Y
LY
Tang
Sydney C W
SC
Lam
Man Fai
MF
Lai
Kar Neng
KN
D000936:Antigen-Antibody Complex / Q000378:metabolism; D002846:Chromatography, Affinity; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D005921:Glomerulonephritis / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000145:classification / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D010316:Particle Size; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D000936:Antigen-Antibody Complex; D007070:Immunoglobulin A