Association of HLA antigens with certain diseases provide insights into genetically determined susceptibility to disease. Although nephrotic syndrome is one of the commonest diseases, it is poorly understood. A group of 57 patients suffering from a minimal lesion nephrotic syndrome (33 patients) and mesangioproliferative glomerulonephritis (24 patients) was studied for immunologic markers. The incidence of HLA-A w 24 is significantly greater in the minimal lesion nephrotic syndrome patients than in controls (18.7% in patients, 0% in controls, p < 0.01). This report fails to show a high incidence of specific HLA antigen in mesangioproliferative glomerulonephritis patients. We believe that the high incidence of HLA-Aw 24 in minimal lesion nephrotic syndrome is indicative of a congenital predisposition to nephrotic syndrome.
Glomerulonephritis/immunology ; HLA Antigens/analysis* ; Human ; Nephrosis, Lipoid/immunology*

We studied 60 cases of minimal change nephrotic syndrome (MCNS) with mesangial IgA deposits occurring over a 6 year period. There were 43 adults and 17 children. Hematuria occurred in 69.0% of the adults and 88.2% of the children. Two adults and six children had gross hematuria during the course of the disease. Mesangial IgA deposits were noted in 100% of the cases, and concomitant IgG or IgM deposits were found in 78.6% of adults and 73.7% of children. The fluorescent intensity of mesangial IgA deposits was trace (+/-) to 1+ in 86.1% and 70.6% of the adults and children respectively. Most of the patients showed electron microscopic findings consistent with minimal change nephrotic syndrome. We speculate that most of our cases are variants of minimal change nephrotic syndrome but are neither IgA nephropathy nor an overlapping syndrome, and that environmental or genetic factors may be related to the deposition of IgA in these MCNS patients.
Adult ; Child ; Comparative Study ; Female ; Glomerular Mesangium/immunology/*pathology ; Hematuria/etiology ; Human ; Immunoglobulin A/*analysis ; Male ; Nephrosis, Lipoid/complications/immunology/*pathology

Childhood minimal change nephrotic syndrome (MCNS) has often been associated with allergic symptoms such as urticaria, bronchial asthma, atopic dermatitis, allergic rhinitis and elevated IgE levels and referred to involve immune dysfunction. Fc epsilon RII is known to be involved in IgE production and response. Interleukin-4 is being recognized as a major cytokine up-regulating IgE production. Hence the present study is aimed at investigating the role of interleukin-4 and Fc epsilon RII in the pathogenesis of MCNS. IgE was measured by ELISA. Fc epsilon RII was analyzed by fluorescence activated cell scanner (FAC-scan) by double antibody staining with anti Leu16-FITC and anti Leu20-PE. Soluble IgE receptor was measured by ELISA using anti CD23 antibody (3-5-14). Interleukin-4 activities were measured by CD23 expression on purified human tonsillar B cells. Serum IgE levels were significantly higher in MCNS (1,507 +/- 680 IU/dl) than in normal controls (123 +/- 99.2 IU/dl). A significantly higher expression of membrane Fc epsilon RII was noted for MCNS (41 +/- 12%) than that in normal controls (18 +/- 6.2%) (p < 0.001). Soluble CD23 levels were also significantly higher in MCNS (198 +/- 39.3%) than in normal controls (153 +/- 13.4) (p < 0.01). Interleukin-4 activity in sera of MCNS (12U/ml) was also significantly higher than normal controls (4.5U/ml). These results indicate that increased production of Fc epsilon RII and interleukin-4 may play an important role in the pathogenesis of MCNS.
B-Lymphocytes/immunology ; Child ; Humans ; Immunoglobulin E/blood ; Interleukin-4/*physiology ; Nephrosis, Lipoid/*etiology/physiopathology ; Receptors, IgE/biosynthesis/*physiology ; Solubility

Animals ; Antibodies, Anti-Idiotypic ; therapeutic use ; Disease Models, Animal ; Doxorubicin ; toxicity ; Immunotherapy ; Interleukin-18 ; immunology ; pharmacology ; Male ; Mice ; Nephrosis, Lipoid ; chemically induced ; pathology ; therapy

OBJECTIVEThe pathogenesis of minimal change nephrotic syndrome (MCNS) remains unclear. This study aimed to investigate the expression of interleukin-6 (IL-6) in rats with doxorubicin-induced nephropathy and its possible roles in the pathogenesis of MCNS.

METHODSEighty-three male Wistar rats were randomly assigned into a control group (n=32) and a nephropathy group (n=51). Nephropathy was induced by a single tail vein injection of doxorubicin (5 mg/kg). The control group was injected with normal saline. Twenty-four-hour urinary protein excretion was measured 7, 14, 28 and 42 days after doxorubicin injection. IL-6 expression in urine and renal tissues was determined using ELISA 7, 14, 28 and 42 days after doxorubicin injection.

RESULTSThe urinary protein excretion increased significantly in the nephropathy group 7, 14, 28 and 42 days after doxorubicin injection compared with that in the control group (P<0.01). IL-6 expression in urine and renal tissues increased significantly 7, 14, 28 and 42 days after doxorubicin injection compared with that in the control group (P<0.01). IL-6 expression in urine and renal tissues was positively correlated with 24-hour urinary protein excretion in the nephropathy group (r=0.794, P<0.01; r= 0.870, P<0.01). IL-6 expression in urine was positively correlated with that in renal tissues (r=0.739, P<0.01).

CONCLUSIONSIL-6 expression in the urine and renal tissues is increased in MCNS rats. IL-6 might play an important role in the pathogenesis of MCNS.

Animals ; Antibiotics, Antineoplastic ; toxicity ; Disease Models, Animal ; Doxorubicin ; toxicity ; Interleukin-6 ; analysis ; Kidney ; chemistry ; Male ; Nephrosis, Lipoid ; chemically induced ; immunology ; Rats ; Rats, Wistar

OBJECTIVETo study the significance of trace immunoglobulin M (IgM) deposits in glomerular mesangium in children with minimal change primary nephrotic syndrome (PNS).

METHODSOne hundred and six children who were clinically diagnosed with PNS and pathologically diagnosed with minimal change disease (MCD) and trace deposition of IgM in renal tissues were enrolled as subjects. Eighty-one PNS children with MCD but no deposition of immune complexes were used as the control group. The clinical characteristics and efficacies of glucocorticoids and immunosuppressants were retrospectively analyzed in the two groups. All patients were given full-dose prednisone by oral administration, and patients with glucocorticoid resistance or frequent relapses were additionally given immunosuppressants.

RESULTSThe incidence of glucocorticoid resistance in the IgM deposit group was significantly higher than that in the control group (27.2% vs 12.3%; P<0.05). The incidence of frequent relapses in the IgM deposit group was also significantly higher than that in the control group (48.1% vs 10.4%; P<0.05). The complete remission rate for glucocorticoid-resistant patients treated with prednisone combined with mycophenolate mofetil (MMF) was 68% and 62% respectively in the IgM deposit and control groups (P>0.05). The relapse frequency in patients with frequent relapses was significantly reduced in both groups after treatment with prednisone and MMF in combination (P<0.05).

CONCLUSIONSTrace deposition of IgM in renal tissues may be an important factor for glucocorticoid resistance and frequent relapses in PNS children with MCD. Prednisone combined with MMF may be a better choice in the treatment of patients with glucocorticoid resistance or frequent relapses.

Adolescent ; Child ; Child, Preschool ; Drug Resistance ; Female ; Glomerular Mesangium ; immunology ; Glucocorticoids ; therapeutic use ; Humans ; Immunoglobulin M ; analysis ; Immunosuppressive Agents ; therapeutic use ; Infant ; Male ; Nephrosis, Lipoid ; drug therapy ; immunology ; Retrospective Studies

OBJECTIVETo study the expression of neonatal Fc receptor in podocytes in human nephritis and immune-induced rat nephritis models: anti-Thy1.1 nephritis and Heymann nephritis.

METHODSThirty-nine cases of renal biopsies were enrolled from September 2009 to February 2010, including 8 cases of minimal change disease, 4 cases of focal segmental glomerulosclerosis, 9 cases of membranous nephropathy, 12 cases of IgA nephropathy and 6 cases of lupus nephritis. Five normal kidney tissue samples adjacent to renal clear-cell carcinoma were served as normal controls. Laser capture microdissection and real-time RT-PCR were used to assess the expression level of FcRn mRNA in glomeruli of various glomerulonephritides, and immunohistochemistry (IHC) of FcRn by SuperVision method was performed. In addition, rat models of mesangial proliferative nephritis (anti-Thy1.1 nephritis) and passive membranous nephropathy (Heymann nephritis) were established and FcRn was examined in renal tissues by IHC.

RESULTSThe FcRn mRNA level in lupus nephritis was statistically higher than that of normal controls (P < 0.05). FcRn protein expression by IHC was seen in lupus nephritis (6/6), membranous nephropathy (6/9) and IgA nephropathy (7/12), significantly higher than that of normal controls (0/5), P < 0.05. Minimal change disease and focal segmental glomerular sclerosis showed minimal or none expression of FcRn (1/8, 0/4 respectively) and not statistically difference from that of normal controls. Furthermore, FcRn expression in podocytes was detected in rat anti-Thy1.1 (3/5) and Heymann nephritis models (2/7) but was not detected in normal controls.

CONCLUSIONSExpression of FcRn in podocytes was up-regulated in immune-induced human nephritis and rat nephritis models of anti-Thy1.1 nephritis and Heymann nephritis. FcRn may play a role in the development of immune-induced glomerulonephritis.

Animals ; Glomerulonephritis, IGA ; metabolism ; pathology ; Glomerulonephritis, Membranous ; metabolism ; pathology ; Glomerulosclerosis, Focal Segmental ; metabolism ; pathology ; Histocompatibility Antigens Class I ; genetics ; metabolism ; Humans ; Laser Capture Microdissection ; Lupus Nephritis ; metabolism ; pathology ; Male ; Nephritis ; genetics ; immunology ; metabolism ; pathology ; Nephrosis, Lipoid ; metabolism ; pathology ; Podocytes ; metabolism ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Receptors, Fc ; genetics ; metabolism ; Thy-1 Antigens ; immunology ; metabolism ; Up-Regulation