N. Yano et al., INVOLVEMENT OF INTEULEUKIN-4 AND SOLUBLE CD23 IN HYPERSYNTHESIS OF IMMUNOGLOBULIN-A AND IMMUNOGLOBULIN-E IN PATIENTS WITH IGA NEPHROPATHY, Nephron, 72(1), 1996, pp. 44-51
To determine the cytokines responsible for the increase in production
of IgA in patients with IgA nephropathy (IgAN), the roles of interleuk
in-4 (IL-4) and soluble CD23 (sCD23) were examined. Peripheral blood m
ononuclear cells (PBMCs) and serum were obtained from 24 patients with
IgAN and 14 patients with non-IgA proliferative glomerulonephritis. T
wenty healthy adults served as controls. Concentrations of IgA and IgE
in 10-day culture supernatants of PBMCs were measured by the sandwich
ELISA method. Levels of sCD23 and activities of IL-4 in LC-day (96-ho
ur) culture supernatants and serum were measured by ELISA and bioassay
, respectively. Activities of IL-4 both in culture supernatants and se
rum were significantly elevated in patients with IgAN compared with co
ntrols (1.26 +/- 0.53 vs. 0.68 +/- 0.37 U/ml in culture supernatants,
p < 0.05; 1.35 +/- 1.34 vs. 0.89 +/- 0.82 U/ml in serum, p < 0.05). Le
vels of sCD23 in IgAN patients' serum were also significantly elevated
(521.7 +/- 514.9 vs. 173.0 +/- 166.2 U/ml, p < 0.01). In vitro IgA an
d IgE synthesis were suppressed by anti-IL-4 monoclonal antibody (mAb)
only when the antibody was added on the day when the culture was star
ted (day 0). No suppression of IgA or IgE synthesis was observed when
the antibody was added on day 4. IgE but not IgA synthesis was suppres
sed by anti-CD23 mAb when added on both days 0 and 4. Serum levels of
IgE showed positive correlations with serum activities of IL-4 and wit
h levels of serum sCD23. It is concluded that IL-4 and sCD23 might pla
y decisive roles in in vitro and in vivo hyperproduction of IgA. and I
gE in patients with IgAN, and that sCD23 seemed to control IgE but not
IgA synthesis through a unique pathway.