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IgA Nephropathy (iga + nephropathy)
Selected AbstractsFc, receptor I activation induces leukocyte recruitment and promotes aggravation of glomerulonephritis through the FcR, adaptorEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2007Yutaka Kanamaru Abstract Myeloid cells bear Fc receptors (FcR) that mediate inflammatory signaling through the ITAM-containing FcR, adaptor. They express FcR,-associated Fc,RI, which modulate either activating or inhibitory signaling depending on the type of ligand interaction. The role of Fc,RI, in disease progression remains unknown, notably in IgA nephropathy (IgAN), one of major causes of end-stage renal disease, in which large amounts of circulating IgA-immune complexes (IC) may mediate receptor activation. To analyze the involvement of Fc,RI activation in glomerulonephritis (GN), we generated Tg mice expressing a mutated, signaling-incompetent, human Fc,RIR209L that cannot associate with FcR,. Like Fc,RIwt -Tg mice, they developed mesangial IgA deposits but not macrophage infiltration. Fc,RI activation in Fc,RIwt, but not in Fc,RIR209L, Tg mice resulted in marked inflammation with severe proteinuria and leukocyte infiltration in spontaneous IgAN or anti-glomerular basement membrane Ab-induced GN models. Receptor triggering of syngenically transferred Fc,RIwt Tg macrophages into non-Tg animals induced their recruitment into injured kidneys during GN development. Fc,RIwt cross-linking on macrophages activated MAP kinases and production of TNF-, and MCP-1. Moreover, IgA-IC from IgAN patients activated Fc,RI and induced TNF-, production. Thus, Fc,RI activation mediates GN progression by initiating a cytokine/chemokine cascade that promotes leukocyte recruitment and kidney damage. [source] Effects of human interleukin-18 and interleukin-12 treatment on human lymphocyte engraftment in NOD-scid mouseIMMUNOLOGY, Issue 2 2002Hidenobu Senpuku Summary NOD/LtSz- prkdcscid/prkdcscid (non-obese diabetic-severe combine immunodeficiency; NOD-scid) mice grafted with human peripheral blood lymphoid cells have been used as an in vivo humanized mouse model in various studies. However, cytotoxic human T cells are induced in this model during immune responses, which gives misleading results. To assist in grafting of human lymphocytes without the induction of cytotoxic human T cells, we investigated the effects of T helper type 1 (Th1) and Th2 cytokines on human lymphocyte grafting and migration, as well as the production of immunoglobulin deposited in glomeruli and human immunodeficiency virus-1 (HIV-1) infection using NOD-scid mice. Administration of interleukin-18 (IL-18) and IL-12 enhanced the grafting of human CD4+ and CD8+ T cells in the mice, whereas co-administration prevented grafting due to interferon-,-dependent apoptosis. Immunoglobulin A (IgA) deposits were observed in mice treated with IL-18 alone, but not in those given phosphate-buffered saline, IL-12 alone, or IL-18 + IL-12. A high rate of HIV infection was also observed in the IL-18-treated group. Together, these results indicate that IL-18 may be effective for the grafting and migration of CD4+ and CD8+ T cells, except for the induction of apoptosis and regulation of class-switching IgA. IL-18-administered NOD-scid mice provide a useful small humanized model for the study of HIV infection and IgA nephropathy. [source] Prediction of diagnosis of immunoglobulin a nephropathy prior to renal biopsy and correlation with urinary sediment findings and prognostic gradingJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2008Kazutaka Nakayama Abstract Several clinical markers correlate well with the diagnosis and prognosis of IgA nephropathy (IgAN). In the present study, we re-evaluated the usefulness of these four clinical markers for prediction of the diagnosis of patients with IgAN through a comparison between many more patients with IgAN and those with other types of renal diseases. 364 patients with IgAN and 289 with other types of renal disease were examined. An analysis was performed prior to renal biopsy, using clinical markers including, serum IgA, serum IgA/C3 ratio, number of red blood cells in urinary sediments, and urinary protein. Patients with IgAN were divided into four groups according to histopathological findings. Presence of microscopic hematuria, persistent proteinuria, high serum IgA levels, and the serum IgA/C3 ratios are useful for prediction of diagnosis of IgAN and distinguishing it from other renal diseases. Blood pressure, urinary protein, serum uric acid, renal function, and urinary sediment findings may be useful for prediction of prognostic grading in patients with IgAN. J. Clin. Lab. Anal. 22:114,118, 2008. © 2008 Wiley-Liss, Inc. [source] Relationship between renal anemia and prognostic stages of IgA nephropathyJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2005Seiki Aruga Abstract In 2002, the Joint Committee of the Special Study Group on Progressive Glomerular Diseases, Ministry of Health, Labor and Welfare of Japan newly revised the clinical guidelines for IgA nephropathy (Sakai et al.: Jpn J Nephrol 37:417,421, 1995; Tomino and Sakai: Clin Exp Nephrol, 7, 93,97, 2003). The prognostic stages were classified into four groups: the good prognosis group (Group I), relatively good prognosis group (Group II), relatively poor prognosis group (Group III), and poor prognosis group (Group IV). The relationship between the levels of Hb, Ht, and RBC in peripheral blood and the renal prognostic stages was determined in 62 patients with IgA nephropathy in the present study. The mean levels of Hb, Ht, and RBC were significantly lower in Group IV than in Group I (P<0.05). However, there were no significant changes in the levels of serum creatinine (s-Cr) or creatinine clearance (CCr) among these four groups. It appears that the levels of Hb, Ht, and RBC in peripheral blood may be important clinical parameters for the evaluation of prognostic stages in patients with IgA nephropathy. J. Clin. Lab. Anal. 19:80,83, 2005. © 2005 Wiley-Liss, Inc. [source] Relationship between levels of urinary type IV collagen and renal injuries in patients with IgA nephropathyJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 1 2004Hiroaki Io Abstract Because type IV collagen is synthesized by podocytes and mesangial cells, we investigated the relationship between levels of urinary type IV collagen (uIV) and renal injuries in patients with IgA nephropathy. uIV was measured by a highly sensitive one-step sandwich enzyme immunoassay prior to renal biopsy. Patients with IgA nephropathy were classified into four grades (grade 1 = good prognosis, grade 2 = relatively good prognosis, grade 3 = relatively poor prognosis, and grade 4 = poor prognosis) by the prognostic criteria of the Ministry of Health, Labor, and Welfare of Japan. Levels of uIV in grade 4 were significantly higher than those in grades 1,3. These levels tended to increase gradually due to progression of renal injuries. The grades were further divided into two groups: group I (good or relatively good prognoses) and group II (relatively poor or poor prognoses). Patients with proteinuria of <1.0 g/day were defined as groups Ip and IIp. The levels of uIV in group II were significantly higher than those in group I, and those in group IIp were significantly higher than those in group Ip. It appears that the level of uIV can be a useful marker for detection of renal injuries in IgA nephropathy. J. Clin. Lab. Anal. 18:14,18, 2004. © 2004 Wiley-Liss, Inc. [source] Increased sialylation of polymeric ,-IgA1 in patients with IgA nephropathyJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 1 2002Joseph C.K. Leung Abstract The mechanism of mesangial IgA deposition is poorly understood in IgA nephropathy (IgAN). Abnormal glycosylation of carbohydrate moieties in the hinge region of the IgA molecule has recently attracted much attention. In this report, we studied galactosylation and sialylation profiles in ,- and ,-IgA1 from patients with IgAN. Total serum IgA1 was isolated from patients with IgAN or healthy controls by jacalin-affinity chromatography. Six fractions of molecular weight (MW) 50,1,000 kDa were separated by fast protein liquid chromatography (FPLC). Four lectin-binding assays were used to study the sialylation and the presence of terminal galactose or N-acetylgalactosamine (GalNAc) in the O-linked carbohydrate moieties of ,- or ,-IgA1. Maackia amurensis agglutinin (MAA) and Sambucus nigra agglutinin (SNA) lectin recognize ,(2,3)- and ,(2,6)-linked sialic acid, respectively. Peanut agglutinin (PNA) and Helix aspersa (HA) lectin recognize terminal galactose and GalNAc, respectively. Reduced HA was demonstrated in macromolecular , or ,-IgA1 (300,825 kDa) isolated from patients with IgAN (P < 0.05 compared with healthy controls). Lambda- but not ,-IgA1 from patients with IgAN bound less to PNA (P < 0.05). The ,(2,3)-linked sialic acid content in ,- but not ,-IgA1 of MW 150,610 kDa from patients was higher than that of controls (P < 0.005). The ,(2,6)-linked sialic acid content in ,-IgA1 (300,825 kDa) and ,-IgA1 (150,610 kDa) from patients was also higher than that of controls. This unusual glycosylation and sialylation pattern of the ,-IgA1 may have important implications for the pathogenesis of IgAN, as both the masking effect of sialic acid on galactose and the reduced galactosylation will hinder the clearance of macromolecular ,-IgA1 by asialoglycoprotein receptor of hepatocytes. The negative charge from sialic acid may also favor mesangial deposition of macromolecular ,-IgA1 in IgAN. J. Clin. Lab. Anal. 16:11,19, 2002. © 2002 Wiley-Liss, Inc. [source] A family with IgA nephropathy and hereditary lymphoedema praecoxJOURNAL OF INTERNAL MEDICINE, Issue 5 2002M. USTA Abstract.,Usta M, Dilek K, Ersoy A, Alper E, Özbek S, Özdemir B, Filiz G, Yavuz M, Güllülü M, Yurtkuran M (Uluda, University Medical School, Bursa, Turkey). A family with IgA nephropathy and hereditary lymphoedema praecox (Case Report). J Intern Med 2002; 251: 447,451. Immunoglobulin A (IgA) nephropathy is the most common primary glomerulonephritis worldwide. The pathogenesis is still unknown and treatment has not yet been established. Rarely it can be associated with other disorders. Its association with hereditary lymphoedema is not reported before. We report four patients, a 60-year-old father, his two sons and his daughter, with hereditary lymphoedema. The family had nine members and in four of them lymphoedema was evident. The other members had neither lymphoedema nor IgA nephropathy. This is the first report of IgA nephropathy in association with hereditary lymphoedema. [source] Clinical features of acute renal failure associated with hepatitis A virus infectionJOURNAL OF VIRAL HEPATITIS, Issue 9 2010Y. J. Jung Summary., Acute hepatitis A (AHA) is one of the most common infectious diseases; it is usually a self-limiting disease affecting the liver. Although extrahepatic manifestations are not common, some cases have been reported associated with acute renal failure. We reviewed the clinical features of patients with AHA complicated by acute renal failure (ARF group) and compared them with patients with noncomplicated AHA (non-ARF group). The medical records of 208 consecutive patients with AHA who were diagnosed between January 2003 and October 2008 were reviewed. We identified 15 patients (7.2%) with ARF associated with AHA. There were no differences between the ARF and non-ARF group with regard to gender and age. The peak value of alanine aminotransferase (ALT) (median: 6060 IU/L vs 1792 IU/L, P < 0.001), prothrombin time (PT) (International normalized ratio, median 1.72 vs 1.10, P < 0.001), and total bilirubin level (median: 9.6 mg/dL vs 6.3 mg/dL, P = 0.04) were significantly higher in the ARF than in the non-ARF group. Twelve patients (80%) recovered completely with haemodialysis (seven patients, 46.7%) or only conservative management (five patients, 33.3%), while one patient underwent liver transplantation because of fulminant hepatic failure, and two patients died because of fulminant hepatic failure. There were no deaths among patients with noncomplicated AHA in the non-ARF group. Five patients underwent kidney biopsy; two patients were diagnosed with acute tubular necrosis, two patients with acute interstitial nephritis with IgA nephropathy and one patient with acute tubulointerstitial nephritis. All patients in the ARF group had microscopic haematuria and proteinuria (100%vs 31.1%, P < 0.001). Urine sodium levels were more than 10 mEq/L in 10 patients. The findings of high urinary sodium concentrations, microscopic haematuria and proteinuria did not support the diagnosis of hepatorenal syndrome (HRS). Patients with AHA with ARF had higher ALT levels, more prolonged PTs, and higher total bilirubin levels. The prognosis for these patients was poorer than for those without ARF. However, the patients with ARF and nonfulminant AHA had recovered with proper treatment and should not be confused with patients that have HRS. [source] Mesangial cell proliferation inhibitors for the treatment of proliferative glomerular diseaseMEDICINAL RESEARCH REVIEWS, Issue 1 2003Yasuhisa Kurogi Abstract Mesangial cells (MC) serve a number of functions in the renal glomerular capillary including structural support of the capillary tuft, modulation of glomerular hemodynamics, and a phagocytic function allowing removal of macromolecules and immune complexes. The proliferation of MC is a prominent feature of glomerular disease including IgA nephropathy, membranoproliferative glomerulonephritis, lupus nephritis, and diabetic nephropathy. In experimental animal models of nephritis, MC proliferation frequently precedes and is linked to the increase of extracellular matrix in the mesangium and glomerulosclerosis. Reduction of MC proliferation in glomerular disease models by treatment with heparin, low-protein diet, or antibodies to platelet-derived growth factor (PDGF), have been shown to reduce extracellular matrix expansion and glomerulosclerotic changes. Therefore, MC proliferation inhibitors may offer therapeutic opportunities for the treatment of proliferative glomerular disease. It is also known that the MC proliferation is inhibited by many kinds of pharmacological drugs, for example, angiotensin converting enzyme (ACE) inhibitors, leukotriene D4 (LTD4) antagonists, PDGF inhibitors, matrix metalloproteinases (MMP) inhibitors, 3-hydroxy-3 methyl glutaryl-coenzymeA (HMG-CoA) inhibitors, cyclin-dependent kinases (CDK) inhibitors, and others. This review summarizes the recently reported MC proliferation inhibitors with their pharmacological properties on the basis of their chemical structures. © 2002 Wiley Periodicals, Inc. Med Res Rev, 23, No. 1, 15,31, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10028 [source] Statins and progressive renal diseaseMEDICINAL RESEARCH REVIEWS, Issue 1 2002Michele Buemi Abstract Thanks to the administration of hypocholesterolemic drugs, important advances have been made in the treatment of patients with progressive renal disease. In vitro and in vivo findings demonstrate that statins, the inhibitors of HMG-CoA reductase, can provide protection against kidney diseases characterized by inflammation and/or enhanced proliferation of epithelial cells occurring in rapidly progressive glomerulonephritis, or by increased proliferation of mesangial cells occurring in IgA nephropathy. Many of the beneficial effects obtained occur independent of reduced cholesterol levels because statins can directly inhibit the proliferation of different cell types (e.g., mesangial, renal tubular, and vascular smooth muscle cells), and can also modulate the inflammatory response, thus inhibiting macrophage recruitment and activation, as well as fibrosis. The mechanisms underlying the action of statins are not yet well understood, although recent data in the literature indicate that they can directly affect the proliferation/apoptosis balance, the down-regulation of inflammatory chemokines, and the cytogenic messages mediated by the GTPases Ras superfamily. Therefore, as well as reducing serum lipids, statins and other lipid-lowering agents may directly influence intracellular signaling pathways involved in the prenylation of low molecular weight proteins that play a crucial role in cell signal transduction and cell activation. Statins appear to have important potential in the treatment of progressive renal disease, although further studies are required to confirm this in humans. © 2001 John Wiley & Sons, Inc. Med Res Rev, 22, No. 1, 76,84, 2002 [source] Predictors for progression in immunoglobulin A nephropathy with significant proteinuriaNEPHROLOGY, Issue 2 2010HYEON SEOK HWANG ABSTRACT: Aim: Proteinuria is a primary factor requiring treatment in immunoglobulin (Ig)A nephropathy. The purpose of this study was to assess the relevance of treatment response and relapse of proteinuria with renal function decline. Methods: One hundred and twenty-five biopsy-proven primary IgA nephropathy patients who had more than 1.0 g/day proteinuria at the first assessment were studied. All patients underwent anti-proteinuric treatment, and the association of the rate of renal function decline with treatment responsiveness, clinical and laboratory data was investigated. Results: The treatment response of the patients was: 30.4% complete response (<0.3 g/day proteinuria), 32.8% partial response (0.3,1.0 g/day), 23.2% minimal response (decrement but not reduced to <1 g/day) and 13.6% no response (no decrement of proteinuria). The slope of renal function decline (,1.06 vs,1.24 mL/min per 1.73 m2/year, P = 0.580) was comparable between complete and partial response groups, but they were slower than those of minimal or non-response groups (P < 0.001). In multivariate analysis including other parameters, mean arterial pressure (MAP; , = ,0.240, P = 0.004) during follow up, minimal (, = ,0.393, P < 0.001) and non-response (, = ,0.403, P < 0.001) were significant predictors. In further investigation of complete and partial response groups, MAP (, = ,0.332, P = 0.001) and relapse of proteinuria (, = ,0.329, P = 0.001) were independently associated with slope of renal decline. Conclusion: Achievement of less than 1.0 g/day proteinuria and MAP were important for limiting the loss of renal function, and relapse of proteinuria should be closely monitored in proteinuric IgA nephropathy. [source] Spontaneous animal model, ddY mouse, for studying the pathogenesis and treatment in patients with immunoglobulin A nephropathyNEPHROLOGY, Issue 1 2010YASUHIKO TOMINO ABSTRACT: Immunoglobulin (Ig)A nephropathy has the highest incidence among the various forms glomerulonephritis in the world. The initiating and progressive factors in patients with IgA nephropathy are still obscure. Although there is no specific treatment for patients with IgA nephropathy at present, more clinical trials of new treatments are warranted for such patients. Therefore, it is necessary to clarify those factors and to develop more effective drugs using a spontaneous animal model, the ddY mouse, in the future. [source] School urinalysis screening in KoreaNEPHROLOGY, Issue 2007BYOUNG-SOO CHO SUMMARY: Since 1998, by law, all school children in Korea must have an annual urinalysis. The first early morning urine specimen is examined by a simple dipstick method for the detection of proteinuria, haematuria and glucose. If a urine test is positive, a second test is performed by paediatric nephrologists. We analysed urinalysis data of school urinalysis screening. We also analysed the results of clinical data and the renal biopsy findings of patients referred to our medical centre due to abnormal urinalysis result. To date, about five million students have been screened since annual school urinalysis started in January 1998. Among them, isolated proteinuria was about 0.2%, occult blood was about 0.8%, and glucosuria was about 0.07% from January 1998 to December 2004. Among referred patients, renal biopsy was taken in 63.1% of isolated haematuria, 10.5% of isolated proteinuria and 69.9% of haematuria combined with proteinuria. Histopathological findings are IgA nephropathy in 43.8%, mesangial proliferative glomerulonephritis in 38.4%, Henoch,Schönlein nephritis in 2.7%, membranoproliferative glomerulonephritis in 1.6% and lupus nephritis in 0.5%. Alport disease showed 0.6% as a hereditary disease. In conclusion, the school urinalysis screening could detect chronic renal disease in its early stage. Early detection using school urinalysis screening and confirmatory diagnosis by renal biopsy seems to be helpful for assessment of prognosis and intervention of chronic renal disease progression. [source] Lack of association between NPHS2 gene polymorphisms and sporadic IgA nephropathyNEPHROLOGY, Issue 4 2007JIANHUA MAO SUMMARY: Aim: IgA nephropathy (IgAN) is the most common primary form of glomerulonephritis worldwide. In the present study, the genetic structure of the NPHS2 gene was studied to verify if podocin plays a role in the pathogenesis of IgAN. Methods: Clinical characteristics and DNA samples were collected from 26 Chinese children with sporadic IgAN. A direct sequencing was performed after polymerase chain reaction amplification to all the eight exons of the NPHS2 gene. Results: Three synonymous variants as known polymorphisms (954T,C homozygous, 1038A,G heterozygous and homozygous) were found in 3, 4 and 1 patients, respectively. There was no significant difference in the genotypic and allelic frequencies of 954T > C and 1038A > G polymorphisms between the patients and normal controls. Conclusion: No significant difference in the genotypic and allelic frequencies of the identified 954T > C and 1038A > G polymorphisms between the patients and normal controls was found. [source] Experimental model of IgA nephropathy using KM mouse (second report): Possible protective effect of anti-IgA1 synthetic hinge peptide antibody on glomerular deposition of underglycosylated IgA1NEPHROLOGY, Issue 2006YOSHIYUKI HIKI [source] Role of obesity-related factors in development of IgA nephropathyNEPHROLOGY, Issue 2006KENTARO KOIKE [source] A rapid and convenient method for detecting underglycosylated IgA in sera of patients with IgA nephropathyNEPHROLOGY, Issue 2005DAISUKE KONDO [source] Identification of genes associated with the development of IgA nephropathy: genome-wide screening by SNP markersNEPHROLOGY, Issue 2004Fumihiro AKIYAMA [source] Significant effect of tonsillectomy and oral steroid therapy on clinical remission in patients with IgA nephropathyNEPHROLOGY, Issue 2004Makoto TOMITA [source] Mid-term effects of steroid therapy on childhood-onset IgA nephropathyNEPHROLOGY, Issue 2004Hyogo NAKAKURA [source] Polymorphism of renin-angiotensin system genes in IgA nephropathyNEPHROLOGY, Issue 5 2004KENG-THYE WOO SUMMARY: Background and Aims: Individuals are prone to disease because of certain disease-susceptible genes. The angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D), the angiotensinogen (AGT) gene, M235T, and the angiotensin II type 1 receptor (ATR) gene, A1166C, polymorphisms have been associated with IgA nephropathy (IgAN) and its progression. Several studies on Caucasians and Japanese patients have reported contradictory results. We determined these polymorphisms in 118 Chinese patients with IgAN and 94 healthy Chinese subjects to assess their clinical impact. Methods: Genotyping was performed with DNA isolated from peripheral leucocytes, polymerase chain reaction amplification of the polymorphic sequence, restriction enzymes digestion, and separation and identification of DNA fragments. Clinical data at renal biopsy and final status on renal function were determined from patients' records. Results: Comparing all IgAN patients with controls, AGT and ATR genotype distributions were similar, whereas there was a significant increase in the ACE DD genotype (P < 0.05). When comparing patients with end-stage renal failure (IgAN-ESRF) and those without (IgAN-nonESRF), there was no difference among the three gene polymorphisms. In contrast, there were significant differences in higher male prevalence (P < 0.05), increased serum creatinine at presentation (P < 0.05), more sclerosis (P < 0.01) and higher tubulointerstitial lesion score (P < 0.001) in the IgAN-ESRF group. Conclusion: Among the ACE, AGT and ATR gene polymorphisms, only the DD genotype may predispose the individual to IgAN in the Chinese population. None are significant for prognosticating ESRF. [source] Immunosuppressive treatments for immunoglobulin A nephropathy: A meta-analysis of randomized controlled trialsNEPHROLOGY, Issue 4 2004Review Article SUMMARY: Immunoglobulin A (IgA) nephropathy is a worldwide disease that causes end-stage kidney disease (ESRD) in up to 15,20% of affected patients within 10 years from the apparent onset of disease and in up to 30,40% of individuals within 20 years from diagnosis. No specific treatment has been established and there is wide variation in current practice. This systematic review evaluates the use of immunosuppressive agents to treat patients with IgA nephropathy. The Cochrane Renal Group Specialized Register, Cochrane Controlled Trial Registry, MEDLINE, EMBASE and article reference lists were searched for randomized or quasi randomized trials. Two independent reviewers assessed studies for inclusion criteria (biopsy proven IgA nephropathy, randomized trial, use of immunosuppressive agents) and extracted data regarding the effects of immunosuppressive agents on ESRD, doubling of serum creatinine, glomerular filtration rate, urinary protein excretion and side-effects. Data were analysed with a random effects model. The published trials were few (13 trials, 623 patients) and were generally of poor quality. Compared with placebo, steroids were associated with a lower risk of progression to ESRD (six trials, 341 patients, RR 0.44, 95% CI 0.25,0.80) and lower end-of-trial proteinuria (six trials, 263 patients, weighted mean difference (WMD) ,0.49 g/day, 95% CI ,0.25 to ,0.72). Treatment with alkylating agents significantly reduced end of treatment proteinuria (two trials, 122 patients, WMD ,0.94, 95% CI ,0.46 to ,1.43). Although the optimal management of patients with IgA nephropathy remains uncertain because of limitations with the existing published data, immunosuppressive agents are a promising strategy and should be investigated further. [source] Investigation of serum IgA level and serum IgA/C3 ratio in IgA nephropathyNEPHROLOGY, Issue 2002N IMAI [source] T-cell receptor repertoire in IgA nephropathy renal biopsiesNEPHROLOGY, Issue 2002John F Knight SUMMARY: Renal biopsies from patients with IgA nephropathy (IgAN) were studied to determine whether the presence of ,, and ,, T cells is correlated with disease progression in IgAN. The ,, and ,, T-cell receptor (TCR) repertoire was further analysed in these renal biopsies. Immunohistochemical staining using mAb (TCR, and TCR,) and molecular studies using reverse transcription,polymerase chain reaction (RT-PCR) with primers specific for TCR families were undertaken. CDR3 length spectratyping and sequencing of TCR chains were used to analyse the diversity of the CDR3 region of these receptors. It was demonstrated that the presence of ,, T cells is associated with progressive IgAN while ,, T cells are found in both stable and progressive disease. Analysis of the TCR variable (V), repertoire showed the preferential use of V,8 with marked similarities in the CDR3 region by some renal infiltrating T cells in the kidney of some IgAN patients, although T cells infiltrating the renal interstitium of patients with IgAN express heterogeneous T cell receptors. The data from analysis of ,, T-cell repertoire showed that ,, T cells infiltrating the kidneys of IgAN patients use a restricted subset of ,, T cells with a feature of recurrent junctional amino acid motifs in V,1 T cells. The results suggest that both ,, and ,, T cells are involved in the progression of IgAN to renal failure and also that there is clonal expansion of individual ,, or ,, T cells in the kidneys of some IgAN patients. The conserved amino acid in the TCR CDR3 region of V,8 and the feature of recurrent junctional amino acid motifs in V,1 T cells may indicate antigen-driven selection. [source] Abnormalities of IgA1 production in IgA nephropathyNEPHROLOGY, Issue 2002John FEEHALLY SUMMARY: IgA nephropathy (IgAN) is characterized by the mesangial deposition of polymeric IgA1 (plgA1). the original view that this plgA1 is derived from the mucosal immune system can no longer be sustained. Studies of duodenal mucosa and marrow indicate increased production of plgA1 in the marrow and decreased production in the mucosa. These changes are consistent with immunization studies showing exaggerated and prolonged plgA responses to systemic immunization, and reduced mucosal responses to mucosal neoantigens. However, the IgA1 and IgG systemic responses to mucosal antigen are increased in IgAN, a finding consistent with impairment in oral tolerance, the process by which systemic immune responses, to mucosal antigen challenge are normally suppressed. Both IgA1 production and the induction of oral tolerance are under T-cell control. T-cell populations involved in these processes include ,, T cells, Tr cells and T-helper (Th)3 cells; cytokines with a key role in the control of IgA production include interleukin (IL)-10 and transforming growth factor (TGF)-,. There is evidence of abnormal ,, T-cell V region usage in both mucosa and marrow in IgAN. Increased expression of relevant cytokines has also been reported in circulating T cells in IgAN. the increased O-glycosylation of circulating IgA1 in IgAN may also be further evidence of a shift in the production of mucosal-type plgA1 from the mucosa to marrow. These findings suggest that the specific lymphocyte homing mechanisms that normally maintain oral tolerance and control the site of IgA production require further study in IgAN. [source] IgA nephropathy and mesangial cell proliferation: shared global gene expression profilesNEPHROLOGY, Issue 2002Hideto SAKAI SUMMARY: It is well established that mesangial cell proliferation plays a major role in glomerular injury and progressive renal injury. the expression of a number of different genes has been reported in proliferative mesangial cells in culture. However, the relevance of these genes to renal injury in general and IgA nephropathy (IgAN) remains to be established. Assessment of gene activity on a global genome-wide scale is a fundamental and newly developed molecular strategy to expand the scope of clinical investigation from a single gene to studying all genes at once in a systematic pattern. Capitalizing on the recently developed methodology of high cDNA array hybridization, the simultaneous expression of thousands of genes in primary human proliferating mesangial cells was monitored and compared with renal tissue of IgAN. Complex [,- 33P]-labelled cDNA targets were prepared from cultured mesangial cells, remnant tissue from five IgAN renal biopsies and four nephrectomies (controls). Each target was hybridized to a high-density array of 18 326 paired target genes. the radioactive hybridization signals were analysed by phosphorimager. Approximately 8212±530 different gene transcripts were detected per target. Close to 5% (386±90 genes) were full-length mRNA human transcripts (HT) and the remainder were expressed sequence tags (EST). Using a relational database, electronic subtraction was performed and matching was carried out to allow identification of 203 HT with shared expression in proliferative mesangial cells and IgAN renal biopsies. In addition hierarchical clustering analysis was performed on the HT of IgAN and controls to establish differential expression profiles of mesangial HT in IgAN and controls. Collectively the presented data constitutes a preliminary renal bioinformatics database of the transcriptional profiles in IgAN. More importantly, the information may help to speed up the discovery of genes underlying human IgAN. [source] T-cell receptor repertoire in IgA nephropathy renal biopsiesNEPHROLOGY, Issue 2002John F KNIGHT SUMMARY: Renal biopsies from patients with IgA nephropathy (IgAN) were studied to determine whether the presence of ,, and ,, T cells is correlated with disease progression in IgAN. the ,, and ,, T-cell receptor (TCR) repertoire was further analysed in these renal biopsies. Immunohistochemical staining using mAb (TCR, and TCR,) and molecular studies using reverse transcription-polymerase chain reaction (RT-PCR) with primers specific for TCR families were undertaken. CDR3 length spectratyping and sequencing of TCR chains were used to analyse the diversity of the CDR3 region of these receptors. It was demonstrated that the presence of ,, T cells is associated with progressive IgAN while ,, T cells are found in both stable and progressive disease. Analysis of the TCR variable (V), repertoire showed the preferential use of V,8 with marked similarities in the CDR3 region by some renal infiltrating T cells in the kidney of some IgAN patients, although T cells infiltrating the renal interstitium of patients with IgAN express heterogeneous T cell receptors. the data from analysis of ,, T-cell repertoire showed that ,, T cells infiltrating the kidneys of IgAN patients use a restricted subset of ,, T cells with a feature of recurrent junctional amino acid motifs in V,1 T cells. the results suggest that both ,, and ,, T cells are involved in the progression of IgAN to renal failure and also that there is clonal expansion of individual ,, or ,, T cells in the kidneys of some IgAN patients. the conserved amino acid in the TCR CDR3 region of V,8 and the feature of recurrent junctional amino acid motifs in V,1 T cells may indicate antigen-driven selection. [source] Treatment of IgA nephropathy in childrenNEPHROLOGY, Issue 2002Norishige YOSHIKAWA SUMMARY: IgA nephropathy is the most common primary glomerulonephritis in the world, and about 20,50% of patients develop progressive renal failure. the pathogenesis is still unknown and treatment has not yet been established. Knowledge concerning childhood IgA nephropathy has expanded greatly in the last 10 years, and its importance as the major form of glomerulonephritis and major contributor to end-stage renal disease is also becoming apparent in children. This communication focuses on the treatment of IgA nephropathy in children. [source] Effect of soluble form CTLA-4 on spontaneous IgA nephropathy in ddY miceNEPHROLOGY, Issue 2001K Okano The aim of the present study was to examine the role of CD28-B7 signalling in the development of glomerulonephritis in ddY mice, an animal model for IgA nephropathy. To achieve this aim, we investigated whether the CTLA-4 (CD152) fusion protein, which binds to B7.1 (CD80) and B7.2 (CD86), affects glomerular pathological changes (including IgA deposition), or functional parameters (such as serum creatinine and proteinuria). Each group (n = 4) was given either human CTLA-4 fused with human IgG (CTLA4Ig) or control human IgG1. All treated groups of mice were injected intraperitoneally at a dose of 0.1 mg twice a week for the duration of the study. Mice given control human IgG1 progressively developed typical mesangioproliferative glomerulonephritis, with remarkable glomerular IgA deposits. In contrast, mice treated with CTLA4Ig showed a significant reduction in proteinuria and mesangioproliferative change, with an expansion of the mesangial matrix at 40 weeks of age. The serum IgA levels of these mice were considerably lower than those in mice given the control human IgG1. A direct immunofluorescence study showed the reduction of glomerular IgA deposits in CTLA4Ig-treated mice. We have demonstrated for the first time that the development of spontaneously occurring IgA nephropathy can be prevented in ddY mice by blocking the CD28-B7 interaction using a soluble form of CTLA4Ig. These results suggest that a costimulatory signal via CD28-B7 may play a crucial role in the development and progression of IgA nephropathy. [source] Evaluation by scanning acoustic microscopy (SAM) on glomerular lesion of IgA nephropathyNEPHROLOGY, Issue 2001H Kiyomoto IgA nephropathy (IgAN) is known to commonly cause of end-stage renal failure in Japan. The glomerular lesions of IgAN have histological variations. The determination of prognosis and therapeutic strategy should be carefully done by experts because morphological information from renal biopsies using ordinary optical microscopy is usually qualitative and subjective. Moreover, the histological items for the evaluation of glomerular lesions seems to be unsatisfactory for expression of the disease condition of IgAN. The beneficial properties of scanning acoustic microscopy (SAM) include not only observation of microstructure but also quantitative measurement of acoustic propagation speed (APS), indicating the tissue elasticity. In the present study we compared the APS of glomeruli with the pathological scores that were determined by ordinary light microscopy. We used stocked human renal biopsy specimens diagnosed as IgAN (n = 12) and normal/minimal changes (n = 5). All samples were taken by renal biopsy in Kagawa Medical University Hospital during 1997,2000 under informed consent of the patients. The obtained renal tissue were immersed in 10% formalin and embedded in paraffin. A fixed specimen was consecutively cut into 4 ,m slices. One of the deparaffinized 4 ,m-specimens was directly utilized for SAM without any staining, and the others were stained with haematoxylin-eosin and Masson Trichrome for counting cell number and evaluation of collagen accumulation. For the measurement of glomerular APS, the sample line was set on the equator of the glomerulus and then scanning of the X,Z axis was carried out to obtain the interference fringes that were analysed with a computer imaging software in order to calculate the APS. In light microscopic study, pathological scores were evaluated semiquantitatively by two independent investigators who were unaware of the sample number. Glomerular lesions were scored into five grades and glomerular cell number was also counted in individual glomerulus. The computer-assisted imaging analyser Win ROOF (Mitani, Fukui, Japan) was also used for the determination of glomerular collagen content in specimens stained by Masson Trichrome. A two-dimensional image (C-mode scanning) of SAM enabled imaging of glomerulus in renal biopsy specimen compatible with findings of ordinary light microscopy without staining dye. The glomerular APS in IgAN was significantly higher than in normal/minimal changes. This alteration of glomerular APS in IgAN was positively correlated to both semiquantitative pathological scores and glomerular collagen content determined by light microscopy. However, the cell number of glomelurus did not change between IgAN and normal/minimal change. As a result, we conclude that the glomerular lesion, especially matrix expansion in IgAN, was comparable with the absolute value among specimens. Therefore, it is suggested that SAM method is a novel and useful technique for quantitative evaluation of glomerular lesion in IgAN. [source] | |||||||||||||