Kotaro Osakabe

Impaired cell-mediated immunity in lipoid nephrosis.

Cell-mediated immunity (CMI) was evaluated in 26 patients with lipoid nephrosis (LN), 50 patients suffering from chronic diffuse proliferative glomerulonephritis (CGN) without renal sufficiency and 24 healthy controls. The following parameters were measured: delayed hypersensitivity skin test responses to purified protein derivative (PPD) and candida, circulating lymphocytes. T lymphocytes and T lymphocytes with receptors for the Fc portion of IgG (T gamma cells) or IgM (Tmu cells). Patients with LN in relapse had less mean induration of skin reactivity and a smaller proportion reacting to both antigens as compared with the control subjects. In contrast, the intensity of skin reactivity and the frequency of negative reactions in patients with LN in remission and CGN were similar to those of the control subjects. It was also found that the LN patients in relapse had a significant T lymphocytopenia as well as a significant decrease in absolute numbers of Tmu and T gamma cells, whereas the patients with LN in remission and CGN did not differ significantly from the control population. Thus, the majority of patients with LN in relapse demonstrated an impaired response in a CMI assay system. The disturbed CMI may be secondary to hypoproteinemia and other nutritional factors induced by the nephrotic syndrome.

Concanavalin A-induced suppressor cell activity in lipoid nephrosis.

Suppressor cell activity (SCA) was analysed in 28 patients with lipoid nephrosis (LN) and I patients with chronic proliferative glomerulonephritis (CGN). We have assessed the ability of peripheral blood lymphocytes (PBL) stimulated by concanvalin A(Con A) to inhibit the proliferative response of normal allogeneic lymphocytes by both Con A and phytohaemagglutinin (PHA). It was found that the LN patients in the earlier phase of relapse had significantly increased levels of suppression index (SI) when compared with the values obtained with normal controls. In contrast, the mean suppression values in the PBL from LN patients in remission and CGN patients with or without nephrotic syndrome, whether the mitogen used was Con A or PHA, were similar in those of the control subjects. Moreover, when individual patients were followed through their clinical illness. LN patients had high levels of SI, particularly in the beginning of acute exacerbations; the SI levels then decreased sharply in the latter phase of relapse and again increased to relatively normal levels with the onset of clinical remission. These in vitro findings suggest that there exists an alteration in Con A‐induced SCA in a group of patients with LN.

Defective Cell-Mediated Immunity in Lipoid Nephrosis

Cell-mediated immunity (CMI) was studied in 28 patients with biopsy-proven lipoid nephrosis (LN). The LN patients with nephrotic syndrome (NS) had a significant depression in CMI, characterized by impaired delayed hypersensitivity skin reactivity to purified protein derivative (PPD), depressed local graft-versus-host reaction (GVHR), decreased proportion of T lymphocytes and diminished lymphocyte transformation to phytohemagglutinin (PHA). Concanavalin A (Con A)-induced suppressor cell activity (SCA) was found to be significantly increased in LN patients with NS compared to that in normal individuals. In contrast, the mean levels of CMI and SCA studied in LN patients in remission and in patients with chronic mesangial proliferative glomerulonephritis (CGN) did not differ from normal subjects. Our findings support the notion that at least in some LN patients with the NS, activated suppressor cells are present and possibly account for their decreased CMI.

Impaired Cell-Mediated Immunity in Focal Glomerular Sclerosis

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.

Concanavalin A-Induced Suppressor Cell Activity in Focal Glomerular Sclerosis

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.

Alteration of T-lymphocyte subpopulations in patients with primary renal diseases and systemic lupus erythematosus.

Forty‐eight patients with a variety of primary renal diseases and systemic lupus erythematosus (SLE) were examined for the proportion of circulating T lymphocytes bearing receptors for IgM Tμ cells) or IgG (Tγ cells). Although the control group showed strikingly similar mean values for both Tμ and Tγ cells, the whole group of patients with primary renal diseases and SLE showed a wide scatter of values. Sixteen patients with primary renal diseases and SLE had higher proportions of Tγ cells than the control group, whereas seven patients with chronic glomerulonephritis (CGN), membranoproliferative glomerulonephritis (MPGN), lipoid nephrosis (LN), and SLE showed very marked decrease in the proportions of Tγ cells in the peripheral blood. On the other hand, six out of the total group of patients had low proportions of Tμ cells in the peripheral blood. However, no consistent relationship between the proportion of Tμ and Tγ cells was found in our study. These findings indicate that there exists a heterogeneity of T‐lymphocyte subpopulation distribution in some patients with primary renal diseases and SLE. The possible significance of these phenomena in the pathophysiology of renal diseases is discussed.

Cell-Mediated Immunity in Idiopathic Membranous Nephropathy

Cell-mediated immunity (CMI) was evaluated in 11 patients with idiopathic membranous nephropathy (MN), 50 patients suffering from chronic proliferative glomerulonephritis (CGN) without renal insufficiency and 24 healthy controls. The following parameters were measured: delayed skin reactivity to purified protein derivative (PPD), circulating lymphocytes, lymphocyte cell-surface markers (En and EAC rosettes) and functional markers (mitogenic responses to Con A and PHA). The MN patients with nephrotic syndrome (NS) had less mean induration of skin reactivity and a smaller proportion reacting to the PPD antigen as compared with the control subjects. In contrast, the intensity of skin reactivity and the frequency of negative reactions in MN patients in remission and CGN were similar to those of the control subjects. During the nephrotic stage of MN the proportion of T lymphocytes decreased with simultaneous increase of the proportion of B lymphocytes. It was also found that the MN patients with NS showed impaired lymphocyte reactivity with lower Con A and PHA responses compared to the normal controls. Conversely, the mean mitogenic responses to the antigens in patients with MN in remission and CGN were similar to those of the control subjects. Thus, the majority of MN patients with NS demonstrated an impaired response in a CMI assay system. The possible significance of these phenomena in the pathophysiology of MN is discussed.

Impaired delayed hypersensitivity in lipoid nephrosis

Cell-mediated immunity (CMI) was evaluated in 76 patients with renal disease by summation of delayed cutaneous hypersensitivity (DHS) responses to 4 test antigens, purified protein derivative (PPD), candida, mumps and keyhole limpet hemocyanin (KLH). Patients with lipoid nephrosis (LN) in the nephrotic stage had less mean induration of skin reactivity and a smaller proportion reacting to the former 3 antigens as compared with normal controls or LN patients without the nephrotic syndrome (NS). In contrast, the intensity of skin reactivity and the frequency of negative reactions in LN patients in remission and chronic mesangial proliferative glomerulonephritis (CGN) were similar to those of the control subjects. Immune response to KLH was also impaired in LN patients with the NS as measured by skin testing. The data indicate an impaired DHS in LN and suggest that the impairment relates to the clinical stage of disease.

Concanavalin-A-Induced Suppressor Cell Activity in Idiopathic Membranous Nephropathy

Suppressor cell activity (SCA) was analyzed in 8 patients with idiopathic membranous nephropathy (MN) and in 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 on normal allogenic lymphocytes by both Con A and phytohemagglutinin (PHA). It was found that the MN patients with nephrotic syndrome (NS) had significantly increased levels of suppression index (SI) when compared to the values obtained with normal controls. In contrast, the mean suppression values in the PBL from MN 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 MN patients wih NS demonstrated an alteration in Con-A-induced SCA. The possible significance of these phenomena in the pathophysiology of MN is discussed.

Defective Concanavalin A-Induced Suppressor Cell Activity in Lupus Nephritis

To determine whether patients with systemic lupus erythematosus (SLE) and active nephritis have more profound defects in suppressor cell activity, we studied concanavalin A (Con A)-induced suppressor cell activity (SCA) in 12 patients with lupus nephritis (LN) and 11 patients with chronic mesangial proliferative glomerulonephritis (CGN) without renal insufficiency. The levels of Con A-induced SCA were decreased in patients with LN compared with those in normal controls and those in CGN patients and lower in LN patients with the nephrotic syndrome (NS) than in those without NS. In contrast, the mean responses of Con-A-induced SCA in CGN patients with or without NS did not differ from normal subjects. These findings may lend further insight into the understanding of the immunoregulatory defect in LN.