Hisashi Katayama

Minimal-Change Nephrotic Syndrome Associated with Subcutaneous Eosinophilic Lymphoid Granuloma (Kimura’s Disease)

A 29-year-old Japanese male with a 19-year history of subcutaneous eosinophilic lymphoid granuloma (Kimuras disease) was referred to the Nephrology Service of the Nihon University Hospital for evaluation of edema and massive proteinuria. The renal biopsy disclosed minimal glomerular lesions. In this paper a case of nephrotic syndrome associated with eosinophilic lymphoid granuloma is reported.

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.

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.

Leukocyte Adherence Inhibition Test in Renal Diseases

Leukocyte adherence inhibition (LAI) test was examined in 35 patients with renal diseases and 14 normal controls, using collagenase-treated glomerular basement membrane, glycosidase-treated glomerular basement membrane and renal tubular epithelium as antigens. Although the control group showed strikingly similar mean LAI indices for all antigens tested, the whole group of patients with renal diseases showed a wide scatter of values. Two categories of patients had significantly increased LAI indices (p less than 0.01) when their mean values were compared with those of normal controls: (1) rapidly progressive glomerulonephritis (RPGN) and (2) lupus nephritis (SLE). In the serial studies of the RPGN and SLE cases, there were no significant changes in the pattern of LAI and they continued to give positive and very comparable results when re-examined at intervals of 1-6 months. Out of the 30 patients who were able to be evaluated with the three antigens, 15 cases exhibited positive LAI response to two or more antigens simultaneously. These in vitro findings suggest that there is an abnormal cellular response to certain antigen or widespread LAI reactivity to a variety of renal antigens in certain forms of human glomerulonephritis.