concanavalin-a and Glomerulosclerosis--Focal-Segmental

Lymphocyte ectoenzymes with immunomodulatory function were investigated in 11 children with minimal change disease (MCD), 9 with primary focal segmental glomerulosclerosis (FSGS), and 17 age- and sex-matched healthy children. Basal, concanavalin A (Con A)-, and pokeweed mitogen (PWM)-stimulated lymphocyte ecto-5'-nucleotidase (5'-Nu), dipeptidyl peptidase IV (DPP IV), and alkaline phosphodiesterase I (APD) activities were determined. In MCD relapse ecto-APD activity of unstimulated lymphocytes was higher than controls. Ecto-APD of Con A-stimulated lymphocytes was below controls (23.0, range 7.2-48.7 nmol/min per 10(6) lymphocytes) in all active MCD (18.7, range 7.6-32.6), during corticosteroid treatment (14.6, range 4.5-54), and in remission (13.1, range 6.1-19.6), but was significant only in remission. Con A-stimulated DPP IV was significantly lower from controls (53.8, range 19.3-85.7 nmol/min per 10(6) lymphocytes) in all active MCD (38.1, range 10.8-82.1), during treatment (37.5, range 20.2-58.7), and in remission (39.4, range 24.3-69.6). In FSGS, unstimulated lymphocyte ecto-APD activity was greater than controls. However, Con A-stimulated lymphocyte ecto-APD and DPP IV activities were not significantly different from controls. Con A stimulation of lymphocyte ecto-APD and DPP IV activity was significantly reduced in MCD relapse and in remission, but not in FSGS. Basal, Con A-, and PWM-stimulated ecto-5'-Nu in MCD and FSGS were not different from controls. These results suggest a role for abnormal T cell function in MCD but not in FSGS. The difference in mitogen-stimulated expression of these ectoenzymes suggests a different pathogenesis of childhood MCD and primary FSGS.

Topics: 5'-Nucleotidase; Adolescent; Cells, Cultured; Child; Child, Preschool; Concanavalin A; Dipeptidyl Peptidase 4; Enzyme Activation; Female; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Humans; Lymphocytes; Male; Nephrosis, Lipoid; Phosphodiesterase I; Phosphoric Diester Hydrolases; Pokeweed Mitogens; Proteinuria

Supernatants of peripheral blood mononuclear cell culture from children with minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) were tested for their ability to increase glomerular basement membrane (GBM) permeability and for effects on anionic sites in the GBM. Supernatants from cultures of concanavalin A-stimulated peripheral blood mononuclear cells from patients with MCNS, those with FSGS and normal controls were infused into the renal arteries of normal rats. Infusion of the supernatants from patients with MCNS and FSGS caused a significant reduction of anionic sites in the GBM (p less than 0.001) and a significant increase in urinary albumin excretion (p less than 0.05), whereas infusion of supernatants in control cases did not reduce anionic sites nor increase urinary albumin excretion. These findings show that stimulation of peripheral blood mononuclear cells from MCNS and FSGS with concanavalin A results in liberation of soluble substances which reduce polyanions in the GBM and increases GBM permeability.

Topics: Albuminuria; Animals; Cell Membrane; Cell Membrane Permeability; Cells, Cultured; Child; Concanavalin A; Culture Media; Glomerulosclerosis, Focal Segmental; Humans; Kidney Glomerulus; Male; Monocytes; Nephrosis, Lipoid; Rats; Rats, Inbred Strains; Reproducibility of Results

The response of lymphocytes to Concanavalin A (Con A) was measured in patients with the nephrotic syndrome due to minimal change nephropathy (11 patients), focal glomerulosclerosis (15 patients) and membranous nephropathy (21 patients); autologous serum was not used in these studies. There was a significant reduction in lymphocyte transformation in each group of patients compared to normal controls (p less than 0.01 for each group), but there was no significant difference between the individual groups of patients. Impaired lymphocyte transformation to Con A appears therefore to be a general feature of the nephrotic syndrome and is not exclusive to minimal change nephropathy. Measurements of suppressor cell function in 4 patients with minimal change nephropathy, 9 patients with focal glomerulosclerosis and 12 patients with membranous nephropathy were performed at the same time as the above studies. In each group suppressor cell function was decreased, indicating that the impaired lymphocyte response to Con A is not due to increased suppressor cell activity. These findings do not support the hypothesis that an abnormality of lymphocyte function peculiar to minimal change nephropathy is pathogenetic in that disease and not in other causes of the nephrotic syndrome; it seems more likely that the abnormalities described are secondary to the nephrotic state.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Concanavalin A; Female; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Humans; Lymphocyte Activation; Male; Middle Aged; Nephrosis, Lipoid; T-Lymphocytes, Regulatory

Cell-mediated immunity (CMI) was evaluated in 8 patients with focal glomerular sclerosis (FGS), 50 patients suffering from chronic mesangial proliferative glomerulonephritis without renal insufficiency and 24 healthy controls. The following parameters were measured: delayed skin reactivity to purified protein derivative, circulating lymphocytes, lymphocyte cell-surface markers (neuraminidase-treated sheep erythrocyte and erythrocyte-antibody-complement rosettes) and functional markers (mitogenic responses to concanavalin A and phytohemagglutinin). The FGS patients with nephrotic syndrome (NS) had a significant depression in CMI, characterized by decreased responses of the lymphocytes to both concanavalin A and phytohemagglutinin, impaired delayed hypersensitivity to purified protein derivative and a decreased proportion of T lymphocytes as compared with normal subjects. In contrast, the levels of all CMI parameters studied in FGS patients in remission and in patients with chronic glomerulonephritis with or without NS did not differ from normal subjects. Thus, the majority of FGS patients with NS demonstrated an impaired response in a CMI assay system. The possible significance of these phenomena in the pathophysiology of FGS is discussed.

Topics: Adolescent; Adult; B-Lymphocytes; Concanavalin A; Female; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Humans; Hypersensitivity, Delayed; Intradermal Tests; Leukocyte Count; Lymphocyte Activation; Lymphopenia; Male; Middle Aged; Phytohemagglutinins; T-Lymphocytes

Suppressor cell activity (SCA) was analyzed in 8 patients with focal glomerular sclerosis (FGS) and 11 patients with chronic proliferative glomerulonephritis (CGN). We have assessed the ability of peripheral blood lymphocytes (PBL) stimulated by concanavalin A (Con A) to inhibit the proliferative response of normal allogeneic lymphocytes by both Con A and phytohemagglutinin (PHA). It was found that the FGS patients with nephrotic syndrome (NS) had significantly increased levels of suppression index when compared to the values obtained with normal controls. In contrast, the mean suppression values in the PBL from FGS patients in remission and CGN patients with or without NS, whether the mitogen used was Con A or PHA, were similar to those of the control subjects. Thus, the majority of FGS patients with NS demonstrated an alteration in Con A-induced SCA. The possible significance of these phenomena in the pathophysiology of FGS is discussed.

Topics: Adolescent; Adult; Chronic Disease; Concanavalin A; Female; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Humans; Male; Middle Aged; Nephrotic Syndrome; Phytohemagglutinins; T-Lymphocytes, Regulatory

Sera from patients with the nephrotic syndrome due to minimal change nephropathy (11 patients), membranous nephropathy (14 patients) and focal glomerulosclerosis (15 patients) inhibited the response of normal lymphocytes to the mitogen Concanavalin A. Although there was a tendency for the sera of patients with minimal change nephropathy to be more inhibitory than sera from the other two forms of nephrotic syndrome, this effect of nephrotic sera on normal lymphocytes is not confined to minimal change nephropathy. Until the exact nature of the inhibitor(s) is established, it is therefore not possible to state that impaired lymphocyte transformation by serum plays a pathogenetic role specifically in minimal change nephropathy. The susceptibility of nephrotic patients to infection may be due in part to the sera of the patients causing reduced lymphocyte function in vivo which leads to a defective immune response.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Concanavalin A; Glomerulosclerosis, Focal Segmental; Humans; Lymphocyte Activation; Middle Aged; Nephrosis, Lipoid; Nephrotic Syndrome