A. Chen et al., MONOMERIC IMMUNOGLOBULIN-A PROTECTS GLOMERULUS AGAINST POLYMERIC IMMUNOGLOBULIN-A IMMUNE-COMPLEX IN EXPERIMENTAL IMMUNOGLOBULIN-A NEPHROPATHY, Laboratory investigation, 74(4), 1996, pp. 737-746
Polymeric (p) IgA constitutes 13% of total serum IgA, whereas monomeri
c (m) IgA represents the other 87%. plgA tends to form complexes in th
e circulation that eventually localize in the glomerulus. mlgA is a no
nprecipitable antibody. When complexed with an antigen in vivo, the ci
rculating mlgA immune complex (IC) thus formed does not deposit in the
glomerulus. The purpose of the present study was to evaluate the infl
uence of mlgA on the formation of glgA-IC and subsequent glomerular de
position of the le in an experimental model of IgA nephropathy. The in
fluence of mlgA anti-dinitrophenyl (DNP) on plgA anti-DNP/DNP-conjugat
ed BSA (BSA-DNP) IC formation was assessed by double diffusion test an
d competition PAGE in combination with autoradiography. Only the BSA-D
NP, a model antigen of relatively low molecular mass, was radiolabeled
and monitored throughout the latter experiment. An analysis of cleara
nce kinetics (1 and 6 hours) of the antigen using 4-week-old female BA
LB/c mice, and a series of renal studies were performed after intraven
ous injection with a single dose of combined plgA anti-DNP, BSA-DNP, a
nd mlgA anti-DNP. As demonstrated by the double diffusion test, additi
on of mlgA anti-DNP resulted in suppression of the precipitating react
ion of plgA anti-DNP and BSA-DNP. This effect was confirmed by PAGE fo
r size determination of the BSA-DNP which had been complexed with eith
er plgA anti-DNP or a mixture of plgA anti-DNP and mlgA anti-DNP. The
clearance kinetics studies showed that the elimination of BSA-DNP inje
cted with plgA anti-DNP was prolonged in the presence of mlgA anti-DNP
in a partially dose-dependent manner. The experimental mice receiving
plgA anti-DNP, BSA-DNP, and mlgA anti-DNP showed less hematuria (p <
0.005) than mice receiving plgA anti-DNP and BSA-DNP (positive control
) when examined 1 hour after injection. Immunofluorescence study of th
e renal tissue of mice receiving plgA anti-DNP, BSA-DNP, and mlgA anti
-DNP showed a suppressed glomerular localization of IgA and third comp
onent of complement, as compared with those injected with plgA anti-DN
P and BSA-DNP alone. Similarly, a significant decrease of glomerular B
SA-DNP deposits was observed in mice receiving plgA anti-DNP, BSA-DNP,
and mlgA anti-DNP compared with those receiving plgA anti-DNP and BSA
-DNP alone, as demonstrated by light microscopic autoradiography. Thes
e findings indicate that a high dose of specific mlgA was capable of m
odulating glomerular deposition of the plgA-IC in this animal model of
IgAN.