Involvement of interleukin-4 and soluble CD23 in hypersynthesis of immunoglobulins A and E in patients with IgA nephropathy.
To determine the cytokines responsible for the increase in production of IgA in patients with IgA nephropathy (IgAN), the roles of interleukin-4 (IL-4) and soluble CD23 (sCD23) were examined. Peripheral blood mononuclear cells (PBMCs) and serum were obtained from 24 patients with IgAN and 14 patients with non-IgA proliferative glomerulonephritis. Twenty 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 4-day (96-hour) culture supernatants and serum were measured by ELISA and bioassay, respectively. Activities of IL-4 both in culture supernatants and serum were significantly elevated in patients with IgAN compared with controls (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). Levels 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 and IgE synthesis were suppressed by anti-IL-4 monoclonal antibody (mAb) only when the antibody was added on the day when the culture was started (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 suppressed 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 with levels of serum sCD23. It is concluded that IL-4 and sCD23 might play decisive roles in in vitro and in vivo hyperproduction of IgA and IgE in patients with IgAN, and that sCD23 seemed to control IgE but not IgA synthesis through a unique pathway.
Department of Internal Medicine, School of Medicine, Tokai University, Isehara, Japan.
N
N
Yano
M
M
Endoh
F
F
Takemura
R
R
Naka
A
A
Kashem
Y
Y
Nomoto
H
H
Sakai
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D003404:Creatinine / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000032:analysis / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000378:metabolism; D011507:Proteinuria; D017455:Receptors, IgE / Q000032:analysis / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D017455:Receptors, IgE; D015847:Interleukin-4; D003404:Creatinine