Enhanced beta 2-microglobulin levels in lymphocyte culture supernatants from patients with idiopathic nephrotic syndrome: inhibition of lymphocyte activation by cyclosporine.
Idiopathic nephrotic syndrome (INS) is associated with a disorder of T-lymphocyte function, and an enhanced production of a vasoactive lymphokine, the vascular permeability factor (VPF). In an attempt to evaluate lymphocyte activation in various phases of INS, we measured beta 2-microglobulin (beta 2m) levels in lymphocyte culture supernatants (LCS). In 23 cases of untreated active INS, beta 2m levels in unstimulated LCS were significantly increased in comparison with those of 13 cases of untreated INS in complete remission (p less than 0.001), of 17 cases of active membranous nephropathy (p less than 0.01) and of 14 controls (p less than 0.001). In 13 patients treated with cyclosporine (Cs) (3-4.5 mg/kg/d) during 3 months, beta 2m levels were within the normal range. Although the beta 2m of 7 Cs patients without proteinuria was lower than 5 Cs patients with residual proteinuria, the difference was not statistically significant. In 15 prednisone(Pr)-treated INS patients, beta 2m levels were normalized. However their beta 2m levels were lower in 8 cases of complete remission than in 7 cases of persistent proteinuria (p less than 0.05). Concanavalin-A stimulation increased beta 2m amounts in all groups with a similar magnitude. In vitro addition of Cs (100 ng/ml) inhibited both beta 2m and VPF elevations observed in active INS. beta 2m level and VPF activity were significantly correlated (r = 0.54, p less than 0.01). High levels of beta 2m in LCS from INS are the consequence of an enhanced cellular synthesis and they are inhibited by Pr and Cs. Thus beta 2m increase in INS indeed reflects lymphocyte activation.
Robeva
R
R
INSERM U139, Hôpital Henri Mondor, Creteil, France.
Heslan
J M
JM
Branellec
A
A
Laurent
J
J
Lagrue
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003208:Concanavalin A; D003524:Cyclosporins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000276:immunology*; D011507:Proteinuria / Q000276:immunology; D013997:Time Factors; D001613:beta 2-Microglobulin / Q000032:analysis*
D003524:Cyclosporins; D001613:beta 2-Microglobulin; D003208:Concanavalin A