T cell immunity and phagocytic activity were studied in the blood of patients with IgA nephropathy in order to clarify their roles in the pathogenesis of IgA nephropathy. The percentages of total T lymphocytes, helper T cell and suppressor T cells were significantly reduced in patients. A significantly elevated helper T cell/suppressor T cell ratio in patients showed a predominant reduction in suppressor T cells. There was a significant relationship between histologic findings and helper T cell/suppressor T cell ratio in patients. Natural Killer (NK) cell activity was significantly reduced but the lymphocyte response after phytohemagglutinin (PHA) stimulation was not in patients. ConA-induced suppressor cell activity was not depressed despite of a decrease in suppressor T cells in patients. Phagocytic activity of polymorphonuclear leucocytes (PMNs) ingesting yeasts was significantly reduced in patients. Also an inverse correlation was found between serum IgA levels and phagocytic activity of PMN. It is concluded that suppressor T cell defects, depressed phagocytic activity and impaired NK cell activity may play a role in the pathogenesis of IgA nephropathy.
B-Lymphocytes/immunology ; Glomerulonephritis, IGA/*immunology/pathology ; Humans ; Killer Cells, Natural/immunology ; Neutrophils/immunology ; *Phagocytosis ; T-Lymphocytes/*immunology ; T-Lymphocytes, Regulatory/immunology

OBJECTIVETo study the clinicopathologic features of membranous nephropathy coexisting with IgA nephropathy.

METHODSThe renal biopsies performed in Peking University First Hospital during the period from January, 1998 to April, 2006 were retrospectively reviewed. The clinicopathologic features of 11 cases of membranous nephropathy coexisting with IgA nephropathy were studied. Electron microscopy with immunogold labeling for IgG and IgA were also performed.

RESULTSThe mean age of patients was 39.9 years. The male-to-female ratio was 1:2.9. The patients mainly presented with proteinuria. Proteinuria of nephrotic level was seen in 7 cases (63.6%). Seven cases also had associated microscopic hematuria. None of them showed evidence of renal insufficiency. Cases with secondary diseases, such as hepatitis virus infection and systemic lupus erythematosus, were excluded from the study. Histologically, vacuolation and thickening of glomerular basement membrane was seen. There was also mild mesangial hypercellularity and increase in mesangial matrix. Occasional glomeruli with crescent formation were identified in 2 cases. Immunofluorescence study showed granular staining for IgG and C3 along glomerular capillary walls, in addition to clumps of IgA deposits in mesangium. Electron microscopy revealed subepithelial and mesangial electron-dense deposits. Immunogold labeling showed IgG and IgA localized in the subepithelial and mesangial deposits respectively.

CONCLUSIONMembranous nephropathy coexisting with IgA nephropathy possesses the clinicopathologic features of both components. It might be caused by independent occurrence of the two entities.

Adult ; Female ; Glomerular Basement Membrane ; immunology ; pathology ; ultrastructure ; Glomerular Mesangium ; immunology ; pathology ; ultrastructure ; Glomerulonephritis, IGA ; complications ; immunology ; pathology ; Glomerulonephritis, Membranous ; complications ; immunology ; pathology ; Humans ; Immunoglobulin A ; metabolism ; Immunoglobulin G ; metabolism ; Kidney Glomerulus ; immunology ; pathology ; ultrastructure ; Male ; Middle Aged ; Retrospective Studies

OBJECTIVETo study the difference in clinico-pathological features between IgA nephropathy (IgAN) and Henoch-Schonlein purpura nephritis (HSPN) in children.

METHODSThe medical data of 103 children with HSPN and 61 children with IgAN were retrospectively studied.

RESULTSThere were no significant differences in age, sex and disease course between the HSPN and IgAN groups (P>0.05). Clinical classification demonstrated that more severe conditions were found in the IgAN group than in the HSPN group and gross hematuria was more common in the IgAN group (P<0.05). Serum creatinine and cholesterol levels were higher in the IgAN group than in the HSPN group (P<0.05). Fibrinogen-related antigen deposition was more common in the HSPN group, while complement 3(C3) deposition was more common in the IgAN group. Interstitial fibrosis, tubular casts and tubular inflammatory infiltration were also more common in the IgAN group (P<0.05).

CONCLUSIONSSignificant clinico-pathological differences can be found between HSPN and IgAN in children, and these differences do not support a one disease entity hypothesis.

Child ; Child, Preschool ; Female ; Glomerulonephritis, IGA ; immunology ; pathology ; Humans ; Kidney ; pathology ; Male ; Nephritis ; immunology ; pathology ; Purpura, Schoenlein-Henoch ; immunology ; pathology ; Retrospective Studies

We report a case of glomerular disease with both mesangial IgA and subepithelial IgG deposits in the allograft kidney. The patient was a 36 year-old man who had received a renal allograft 1 year previously. Fifteen days before admission, he discovered a microscopic hematuria without clinical evidences of allograft rejection. Light microscopy showed diffuse increase of mesangial matrix without mesangial cell proliferation. Capillary walls were diffusely and mildly thickened. Immunofluorescence microscopy demonstrated both granular deposits of IgA in the mesangium and IgG along the capillary walls. On electron microscopy, electron-dense deposits were identified not only in the mesangium but also on the epithelial side of the glomerular basement membrane.
Adult ; Case Report ; Glomerulonephritis, IGA/*immunology/pathology ; Human ; Immunoglobulin A/*analysis ; Immunoglobulin G/analysis ; Kidney/*immunology/pathology ; Kidney Transplantation/*immunology ; Male ; Transplantation, Homologous

OBJECTIVETo investigate the relationship between codon 54 gene polymorphism of the host defense molecule, mannose-binding protein (MBP), and the patterns of glomerular immune deposition in IgA nephropathy (IgAN).

METHODSIgAN patients with different patterns of glomerular immune deposition were selected and divided into two groups. Group A consisted of 77 patients with glomerular IgA and C3 deposits, and Group AGM consisted of 70 patients with glomerular IgA, IgG, IgM, C3 and Clq deposits. Clinical features and laboratory relevant data of all patients were collected. One-hundred and forty healthy adults were recruited as normal controls. The MBP gene codon 54 GGC/GAC polymorphism was investigated by using polymerase chain reaction and restriction fragment length polymorphism.

RESULTSThe genotype frequency of GGC/GAC heterozygotes was significantly higher in Group AGM as compared with that of Group A (41.4% vs 19.5%, P < 0.01) or normal subjects (41.4% vs. 26.4%, P < 0.05), while no difference was found in the distribution of MBP genotypes between Group A and normal subjects. GAC allele frequency was also higher in Group AGM than that in Group A (0.24 vs. 0.14, P < 0.05) or normal subjects (0.24 vs. 0.15, P < 0.05). The variant allele (GAC) was markedly associated with Group AGM (OR = 1.95, 95% CI: 1.06 - 3.58). In both Group A and Group AGM, more patients carrying the variant allele had episodes of upper respiratory or gastrointestinal infections prior to the onset of IgAN than those with wild homozygotes (GGC/GGC).

CONCLUSIONSGenetic variation of the host defense molecule, MBP, may be involved in the formation of the diverse patterns of glomerular immune deposition in IgAN. The variant allele of the MBP gene may partially account for abundant immune deposits in some IgAN patients.

Adult ; Alleles ; Carrier Proteins ; genetics ; Collectins ; DNA ; genetics ; Female ; Gene Frequency ; Genetic Variation ; Genotype ; Glomerulonephritis, IGA ; genetics ; immunology ; Humans ; Kidney Glomerulus ; immunology ; pathology ; Male ; Polymorphism, Restriction Fragment Length

Mesangial IgA nephropathy was experimentally induced in ddY mice by oral and parenteral administration of the poliomyelitis vaccine (POLIO), and we then tried to investigate if IgA deposition could be prevented by the concurrent use of sodium cromoglycate (SCG), which is known to inhibit the local mucosal immune reaction. Mucosal and systemic immunity could be induced by the administration of POLIO; proteinuria, increased serum IgA levels, mesangial cell proliferation, mesangial matrix widening, mesangial deposits of IgA, and large electron dense deposits in the mesangium were observed. Concurrent administration of SCG and POLIO resulted in a significant decrease in the serum IgA level and mesangial IgA deposits. The later addition or abstinence of SCG after the 70th day did not influence the glomerular mesangial IgA deposition. But the serum IgA level was still decreased by the continuous treatment of SCG even after the 70th day. Thus, mesangial IgA nephropathy simulating IgA nephropathy in humans could be induced in ddY mice using POLIO and its induction could largely be prevented by the concurrent use of SCG. However mesangial IgA deposits already present could not be cleared by the late administration of SCG.
Animal ; Cromolyn Sodium/*pharmacology ; Female ; Fluorescent Antibody Technique ; Glomerulonephritis, IGA/*immunology/metabolism/pathology ; Immunoglobulin A/metabolism ; Mice ; Microscopy, Electron ; Poliovirus Vaccine, Inactivated/*immunology

OBJECTIVETo investigate the potential of renal pathological index as a differential diagnosis factor for Chinese medicine (CM) syndromes typing in IgA nephropathy (IgAN).

METHODSA total of 1,016 patients with IgAN was recruited from November 2001 to November 2004. All the signs and symptoms including picture of the tongue and pulse tracings were collected. All patients were typed according to the CM syndrome typing scheme for chronic primary glomerulopathy. The severity of glomerulus and tubulointerstitial lesions (mild, moderate-severe) were evaluated using lee's grading system and the Katafuchi score system.

RESULTSThe syndrome types transform in turn by deficiency of both the Spleen (Pi) and Lung (Fei) qi, deficiency of both qi and yin, deficiency of Liver (Gan) and Kidney (Shen) yin and deficiency of Spleen-Kidney (Shen) yang, with the aggravation of pathogenetic condition and that the manifestation of deficiency of qi clinically showed proliferative lesion of glomerular mesangium, while the glomerular sclerosis pathologically showed the manifestation of yin deficiency.

CONCLUSIONRenal pathological findings may be a candidate of objective factors to refine CM syndrome typing process.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Glomerulonephritis, IGA ; classification ; immunology ; pathology ; therapy ; Humans ; Kidney ; blood supply ; pathology ; Kidney Glomerulus ; pathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Renal Artery ; pathology ; Syndrome ; Young Adult

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

OBJECTIVETo study the expression and significance of nestin (a type of cytoskeletal protein) in normal and diseased human kidneys.

METHODSDiseased kidney tissues were obtained from needle biopsies in 32 patients with glomerulonephritis (including 8 cases of membranous glomerulopathy, 3 cases of focal segmental glomerulosclerosis, 17 cases of IgA nephropathy with proteinuria and 4 cases of IgA nephropathy without proteinuria). Control kidney tissues were obtained from nephrectomy specimens for renal tumors. The expression of nestin in the control kidney tissues was studied using immunoelectronic microscopy and immunohistochemistry. The expression of nestin in the diseased kidney tissues was detected by immunohistochemistry and real-time reverse transcription-polymerase chain reaction.

RESULTSIn normal kidney tissues, nestin was detected at the periphery of glomerular capillary loops. Semi-quantitative morphometric analysis showed that the glomerular nestin expression level in cases of IgA nephropathy without proteinuria did not differ from that in the normal controls. However, the glomerular nestin expression levels in cases of IgA nephropathy with proteinuria, membranous glomerulopathy and focal segmental glomerulosclerosis were significantly lower than those in the normal kidneys and IgA nephropathy without proteinuria. The glomerular nestin expression levels inversely correlated with the 24-hour urine protein results.

CONCLUSIONNestin may play an important role in maintaining the normal function of podocytes in human kidney.

Adult ; Gene Expression Regulation ; Glomerulonephritis, IGA ; immunology ; Humans ; Immunohistochemistry ; Intermediate Filament Proteins ; genetics ; metabolism ; Kidney ; Kidney Diseases ; metabolism ; pathology ; Kidney Glomerulus ; metabolism ; pathology ; Middle Aged ; Nephrectomy ; adverse effects ; Nerve Tissue Proteins ; genetics ; metabolism ; Nestin ; Proteinuria ; metabolism

Anti-erythropoietin antibodies usually cross-react with all kinds of recombinant erythropoietins; therefore, erythropoiesis-stimulating agent (ESA)-induced pure red-cell aplasia (PRCA) is not rescued by different ESAs. Here, we present a case of ESA-induced PRCA in a 36-yr-old woman with chronic kidney disease, whose anemic condition improved following reintroduction of darbepoetin-alpha. The patient developed progressive, severe anemia after the use of erythropoietin-alpha. As the anemia did not improve after the administration of either other erythropoietin-alpha products or erythropoietin-beta, all ESAs were discontinued. Oxymetholone therapy failed to improve the transfusion-dependent anemia and a rechallenge with ESAs continuously failed to obtain a sustained response. However, her anemia improved following reintroduction of darbepoetin-alpha at 3 yr after the initial diagnosis. Interestingly, anti-erythropoietin antibodies were still detectable, although their concentration was too low for titration. In conclusion, darbepoetin-alpha can improve ESA-induced PRCA when the anti-erythropoietin antibody titer declines and its neutralizing capacity is lost.
Adult ; Anemia/drug therapy/etiology ; Antibodies/*blood/immunology ; Bone Marrow Cells/pathology ; Drug Hypersensitivity/immunology ; Erythropoietin/*analogs & derivatives/therapeutic use ; Erythropoietin, Recombinant/adverse effects/*immunology/therapeutic use ; Female ; Glomerulonephritis, IGA/complications ; Hematinics/adverse effects/immunology/*therapeutic use ; Humans ; Kidney Failure, Chronic/complications ; Oxymetholone/therapeutic use ; Red-Cell Aplasia, Pure/chemically induced/*drug therapy/immunology