The Experts below are selected from a list of 465 Experts worldwide ranked by ideXlab platform
Stephen Batsford - One of the best experts on this subject based on the ideXlab platform.
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Pathogenesis of poststreptococcal glomerulonephritis a century after Clemens von Pirquet
Kidney International, 2007Co-Authors: Bernardo Rodriguez-iturbe, Stephen BatsfordAbstract:Considerable insight has been gained into the etiopathogenesis of poststreptococcal glomerulonephritis since the landmark theoretical construct of Clemens von Pirquet postulated that disease-causing immune complexes were responsible for the nephritis that followed scarlet fever. Over the years, molecular mimicry between streptococcal products and renal components, autoimmune reactivity and several streptococcal Antigens have been extensively studied. Recent investigations assign a critical role to both in situ formation and deposition of circulating immune complexes that would trigger a variety of effector mechanisms. Glomerular plasmin-binding activity of streptococcal glyceraldehyde-3-phosphate-dehydrogenase may play a role in Nephritogenicity and streptococcal pyrogenic exotoxin B and its zymogen precursor may be the long-sought Nephritogenic Antigen.
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Is the Nephritogenic Antigen in post-streptococcal glomerulonephritis pyrogenic exotoxin B (SPE B) or GAPDH?
Kidney International, 2005Co-Authors: Stephen Batsford, Sergio Mezzano, Michael J. Mihatsch, Emile Schiltz, Bernardo Rodriguez-iturbeAbstract:Is the Nephritogenic Antigen in post-streptococcal glomerulonephritis pyrogenic exotoxin B (SPE B) or GAPDH? Background Acute glomerulonephritis can follow infection by group A streptococci. An immune-complex pathogenesis is accepted, but the causative Antigen(s) is still controversial. In recent years, 2 streptococcal Antigens, the cationic cysteine proteinase exotoxin B (SPE B) and the plasmin receptor, a glyceraldehyde phosphate dehydrogenase (Plr, GAPDH) have attracted attention because: ( 1 ) they were localized in glomeruli in patients with acute post-streptococcal glomerulonephritis (APSGN); and ( 2 ) serum antibody to these Antigens was associated with Nephritogenic streptococcal infections. To date, putative nephritogens were always tested independently. Here, the relevance of SPE B and GAPDH was evaluated in the same renal biopsies and serum samples of well-defined APSGN patients. Methods Renal biopsies (17 patients) and serum samples (53 patients) with APSGN and appropriate controls were examined. Immunofluorescent staining of frozen sections was performed using specific antibodies to SPE B and GAPDH. Serum antibodies were investigated by both enzyme-linked immunosorbent assay (ELISA) and Western blot methodology. Results Glomerular deposits of SPE B were demonstrated in 12/17 APSGN biopsies, and 2 cases were borderline; circulating antibodies were found in all instances (53/53 patients). Glomerular deposition of GAPDH was detected in 1/17 biopsies, and 2 cases were borderline; circulating antibodies were found in 5/47 patients. In 31 control biopsies, only weak staining for each Antigen was found in 2 cases. Conclusion In this study, glomerular deposits of and antibody response to zymogen/SPE B are more consistently present in APSGN than deposits and antibody response to GAPDH. Zymogen/SPE B is likely to be the major Antigen involved in the pathogenesis of most cases of APSGN.
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is the Nephritogenic Antigen in post streptococcal glomerulonephritis pyrogenic exotoxin b spe b or gapdh
Kidney International, 2005Co-Authors: Stephen Batsford, Sergio Mezzano, Michael J. Mihatsch, Emile Schiltz, Bernardo RodrigueziturbeAbstract:BACKGROUND: Acute glomerulonephritis can follow infection by group A streptococci. An immune-complex pathogenesis is accepted, but the causative Antigen(s) is still controversial. In recent years, 2 streptococcal Antigens, the cationic cysteine proteinase exotoxin B (SPE B) and the plasmin receptor, a glyceraldehyde phosphate dehydrogenase (Plr, GAPDH) have attracted attention because: (1) they were localized in glomeruli in patients with acute post-streptococcal glomerulonephritis (APSGN); and (2) serum antibody to these Antigens was associated with Nephritogenic streptococcal infections. To date, putative nephritogens were always tested independently. Here, the relevance of SPE B and GAPDH was evaluated in the same renal biopsies and serum samples of well-defined APSGN patients. METHODS: Renal biopsies (17 patients) and serum samples (53 patients) with APSGN and appropriate controls were examined. Immunofluorescent staining of frozen sections was performed using specific antibodies to SPE B and GAPDH. Serum antibodies were investigated by both enzyme-linked immunosorbent assay (ELISA) and Western blot methodology. RESULTS: Glomerular deposits of SPE B were demonstrated in 12/17 APSGN biopsies, and 2 cases were borderline; circulating antibodies were found in all instances (53/53 patients). Glomerular deposition of GAPDH was detected in 1/17 biopsies, and 2 cases were borderline; circulating antibodies were found in 5/47 patients. In 31 control biopsies, only weak staining for each Antigen was found in 2 cases. CONCLUSION: In this study, glomerular deposits of and antibody response to zymogen/SPE B are more consistently present in APSGN than deposits and antibody response to GAPDH. Zymogen/SPE B is likely to be the major Antigen involved in the pathogenesis of most cases of APSGN.
Bernardo Rodrigueziturbe - One of the best experts on this subject based on the ideXlab platform.
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is the Nephritogenic Antigen in post streptococcal glomerulonephritis pyrogenic exotoxin b spe b or gapdh
Kidney International, 2005Co-Authors: Stephen Batsford, Sergio Mezzano, Michael J. Mihatsch, Emile Schiltz, Bernardo RodrigueziturbeAbstract:BACKGROUND: Acute glomerulonephritis can follow infection by group A streptococci. An immune-complex pathogenesis is accepted, but the causative Antigen(s) is still controversial. In recent years, 2 streptococcal Antigens, the cationic cysteine proteinase exotoxin B (SPE B) and the plasmin receptor, a glyceraldehyde phosphate dehydrogenase (Plr, GAPDH) have attracted attention because: (1) they were localized in glomeruli in patients with acute post-streptococcal glomerulonephritis (APSGN); and (2) serum antibody to these Antigens was associated with Nephritogenic streptococcal infections. To date, putative nephritogens were always tested independently. Here, the relevance of SPE B and GAPDH was evaluated in the same renal biopsies and serum samples of well-defined APSGN patients. METHODS: Renal biopsies (17 patients) and serum samples (53 patients) with APSGN and appropriate controls were examined. Immunofluorescent staining of frozen sections was performed using specific antibodies to SPE B and GAPDH. Serum antibodies were investigated by both enzyme-linked immunosorbent assay (ELISA) and Western blot methodology. RESULTS: Glomerular deposits of SPE B were demonstrated in 12/17 APSGN biopsies, and 2 cases were borderline; circulating antibodies were found in all instances (53/53 patients). Glomerular deposition of GAPDH was detected in 1/17 biopsies, and 2 cases were borderline; circulating antibodies were found in 5/47 patients. In 31 control biopsies, only weak staining for each Antigen was found in 2 cases. CONCLUSION: In this study, glomerular deposits of and antibody response to zymogen/SPE B are more consistently present in APSGN than deposits and antibody response to GAPDH. Zymogen/SPE B is likely to be the major Antigen involved in the pathogenesis of most cases of APSGN.
Stephen R. Holdsworth - One of the best experts on this subject based on the ideXlab platform.
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FMS-like tyrosine kinase 3 ligand treatment does not ameliorate experimental rapidly progressive glomerulonephritis.
PLOS ONE, 2015Co-Authors: Joanna R. Ghali, Kim M. O’sullivan, Peter J. Eggenhuizen, Stephen R. Holdsworth, A. Richard KitchingAbstract:Fms-like tyrosine kinase 3-ligand (FL) is a growth factor that may expand dendritic cell and regulatory T cell populations. We hypothesised that FL-induced regulatory T cells would protect mice from experimental rapidly progressive glomerulonephritis. To determine if FL was able to enhance regulatory T cell populations, C57BL/6 mice received 10 days of daily intraperitoneal injections of either FL or phosphate buffered saline. To induce accelerated autologous-phase anti-mouse glomerular basement membrane glomerulonephritis, mice were sensitized to sheep globulin 4 days prior to the induction of glomerulonephritis with sheep anti-mouse glomerular basement membrane globulin, and experiments ended 10 days later. FL was administered before, throughout and during the sensitization phase of this glomerulonephritis model. Renal disease and systemic immunity to the Nephritogenic Antigen were assessed. FL increased regulatory T cell and plasmacytoid dendritic cell proportions within spleen and lymph nodes. FL administration prior to glomerulonephritis did not protect mice from renal injury. When FL was given throughout the model, FL treated mice had reduced survival, with more interstitial neutrophils and glomerular CD11c+ cells than controls. Systemic immune responses showed increased IL-17A production from splenocytes, with more CD11c+ cells, but reduced plasmacytoid dendritic cell proportions in spleen and lymph nodes, despite increased regulatory T cell proportions. Under homeostatic conditions, FL expanded regulatory T cell and plasmacytoid dendritic cell populations, but FL enhanced systemic inflammatory responses and conventional dendritic cell populations when given during experimental glomerulonephritis, suggesting selective attempts to suppress pathogenic immunity by dendritic cell manipulation may be harmful.
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Cytokine concentrations in stimulated splenocyte supernatant for mice receiving PBS or FL before and during sensitization to the Nephritogenic Antigen in the anti-GBM disease model.
2015Co-Authors: Joanna R. Ghali, Kim M. O’sullivan, Peter J. Eggenhuizen, Stephen R. Holdsworth, Richard A. KitchingAbstract:Data presented as mean±SEM, except for IL-10, presented as median (range) as data is non-parametric. IL-6, IL-12p70 and TNF were not detected.Cytokine concentrations in stimulated splenocyte supernatant for mice receiving PBS or FL before and during sensitization to the Nephritogenic Antigen in the anti-GBM disease model.
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BASIC RESEARCH www.jasn.org T-bet Deficiency Attenuates Renal Injury in Experimental Crescentic Glomerulonephritis
2013Co-Authors: Richard K S Phoon, Richard A. Kitching, Dragana Odobasic, Lynelle K. Jones, Timothy J. Semple, Stephen R. HoldsworthAbstract:T-bet is a transcription factor that is essential for T helper (Th)1 lineage commitment and optimal IFN-� production by CD4 � T cells. We examined the role of T-bet in the development of experimental crescentic glomerulonephritis, which is induced by Th1-predominant, delayed-type hypersensitivity-like responses directed against a Nephritogenic Antigen. Anti-glomerular basement membrane (GBM) glomerulonephritis was induced in T-bet �/ � and wild-type C57BL/6 mice. Compared with wild-type controls, renal injury was attenuated in T-bet �/ � mice with glomerulonephritis, evidenced by less proteinuria, glomerular crescents, and tubulointerstitial inflammation. Accumulation of glomerular CD4 � T cells and macrophages was decreased, and was associated with reduced intrarenal expression of the potent Th1 chemoattractants CCL5/ RANTES and CXCL9/Mig. Supporting the pro-inflammatory nature of T-bet signaling, assessment of systemic immunity confirmed that T-bet �/ � mice had a reduction in Th1 immunity. The kinetic profile of T-bet mRNA in wild-type mice supported the hypothesis that T-bet deficiency attenuates renal injury in part by shifting the Th1/Th2 balance away from a Th1 phenotype. Expression of renal and splenic IL-17A, characteristically expressed by the Th17 subset of effector T cells, which have been implicated in the pathogenesis of autoimmune disease, was increased in T-bet �/ � mice. We conclude that T-bet directs Th1 responses that induce renal injury in experimental crescentic glomerulonephritis. J Am Soc Nephrol 19: 477–485, 2008. doi: 10.1681/ASN.2007030392 The initial description of functionally distinct T helper (Th) cell subsets, Th1 and Th2, 1,2 has provided a useful framework for understanding various diseases. Th1 cells are characterized by the production of proinflammatory cytokines (IFN-�, IL-2, and lymphotoxin-�), mediate cellular immune responses, and play important roles in autoimmunity and clearance of intracellular organisms. In contrast, Th2 cells produc
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T-bet Deficiency Attenuates Renal Injury in
2013Co-Authors: Experimental Crescentic Glomerulonephritis, Richard A. Kitching, Richard K S Phoon, Dragana Odobasic, Lynelle K. Jones, Timothy J. Semple, Stephen R. HoldsworthAbstract:T-bet is a transcription factor that is essential for T helper (Th)1 lineage commitment and optimal IFN-� production by CD4 � T cells. We examined the role of T-bet in the development of experimental crescentic glomerulonephritis, which is induced by Th1-predominant, delayed-type hypersensitivity-like responses directed against a Nephritogenic Antigen. Anti-glomerular basement membrane (GBM) glomerulonephritis was induced in T-bet �/ � and wild-type C57BL/6 mice. Compared with wild-type controls, renal injury was attenuated in T-bet �/ � mice with glomerulonephritis, evidenced by less proteinuria, glomerular crescents, and tubulointerstitial inflammation. Accumulation of glomerular CD4 � T cells and macrophages was decreased, and was associated with reduced intrarenal expression of the potent Th1 chemoattractants CCL5/ RANTES and CXCL9/Mig. Supporting the pro-inflammatory nature of T-bet signaling, assessment of systemic immunity confirmed that T-bet �/ � mice had a reduction in Th1 immunity. The kinetic profile of T-bet mRNA in wild-type mice supported the hypothesis that T-bet deficiency attenuates renal injury in part by shifting the Th1/Th2 balance away from a Th1 phenotype. Expression of renal and splenic IL-17A, characteristically expressed by the Th17 subset of effector T cells, which have been implicated in the pathogenesis of autoimmune disease, was increased in T-bet �/ � mice. We conclude that T-bet directs Th1 responses that induce renal injury in experimental crescentic glomerulonephritis. J Am Soc Nephrol ●●: –, 2008. doi: 10.1681/ASN.2007030392 The initial description of functionally distinct T helper (Th) cell subsets, Th1 and Th2, 1,2 has provided a useful framework for understanding various diseases. Th1 cells are characterized by the production of pro-inflammatory cytokines (IFN-�, IL-2, and lymphotoxin-�), mediate cellular immune responses, and play important roles in autoimmunity and clearance of intracellular organisms
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Brief Definitive Report Major Histocompatibility Complex Class II Expression by Intrinsic Renal Cells Is Required for Crescentic
2013Co-Authors: Christian Kurts, Frank Köntgen, Stephen R. HoldsworthAbstract:The requirement for major histocompatibility complex class II (MHC II) to initiate immune renal injury was studied in a murine model of CD4 � T cell–dependent crescentic glomerulonephritis (GN). C57BL/6 (MHC II �/ � ) mice developed crescentic GN with glomerular CD4 � T cell infiltration and renal injury, in response to a Nephritogenic Antigen (sheep globulin) planted on their glomerular basement membrane. MHC II–deficient C57BL/6 mice (MHC II �/ � ) did not develop crescentic GN, CD4 � T cell infiltration, or injury, indicating that this form of immune glomerular injury is MHC II dependent. The requirement for MHC II expression by intrinsic renal cells was studied in chimeric mice, which expressed MHC II on bone marrow–derived cells and in the thymus, but not in the kidneys. These chimeric mice had normal T and B cell populations and MHC II expression in their spleens and lymph nodes and developed an immune response to systemically and cutaneously administered sheep globulin. However, they did not develop crescentic GN, CD4 � T cell infiltration, or renal injury in response to the sheep globulin planted in their glomeruli. These studies demonstrate that interaction of CD4 � T cells with intrinsic renal cells expressing MHC II is required for development of cell-mediated immune renal injury
Emile Schiltz - One of the best experts on this subject based on the ideXlab platform.
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Is the Nephritogenic Antigen in post-streptococcal glomerulonephritis pyrogenic exotoxin B (SPE B) or GAPDH?
Kidney International, 2005Co-Authors: Stephen Batsford, Sergio Mezzano, Michael J. Mihatsch, Emile Schiltz, Bernardo Rodriguez-iturbeAbstract:Is the Nephritogenic Antigen in post-streptococcal glomerulonephritis pyrogenic exotoxin B (SPE B) or GAPDH? Background Acute glomerulonephritis can follow infection by group A streptococci. An immune-complex pathogenesis is accepted, but the causative Antigen(s) is still controversial. In recent years, 2 streptococcal Antigens, the cationic cysteine proteinase exotoxin B (SPE B) and the plasmin receptor, a glyceraldehyde phosphate dehydrogenase (Plr, GAPDH) have attracted attention because: ( 1 ) they were localized in glomeruli in patients with acute post-streptococcal glomerulonephritis (APSGN); and ( 2 ) serum antibody to these Antigens was associated with Nephritogenic streptococcal infections. To date, putative nephritogens were always tested independently. Here, the relevance of SPE B and GAPDH was evaluated in the same renal biopsies and serum samples of well-defined APSGN patients. Methods Renal biopsies (17 patients) and serum samples (53 patients) with APSGN and appropriate controls were examined. Immunofluorescent staining of frozen sections was performed using specific antibodies to SPE B and GAPDH. Serum antibodies were investigated by both enzyme-linked immunosorbent assay (ELISA) and Western blot methodology. Results Glomerular deposits of SPE B were demonstrated in 12/17 APSGN biopsies, and 2 cases were borderline; circulating antibodies were found in all instances (53/53 patients). Glomerular deposition of GAPDH was detected in 1/17 biopsies, and 2 cases were borderline; circulating antibodies were found in 5/47 patients. In 31 control biopsies, only weak staining for each Antigen was found in 2 cases. Conclusion In this study, glomerular deposits of and antibody response to zymogen/SPE B are more consistently present in APSGN than deposits and antibody response to GAPDH. Zymogen/SPE B is likely to be the major Antigen involved in the pathogenesis of most cases of APSGN.
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is the Nephritogenic Antigen in post streptococcal glomerulonephritis pyrogenic exotoxin b spe b or gapdh
Kidney International, 2005Co-Authors: Stephen Batsford, Sergio Mezzano, Michael J. Mihatsch, Emile Schiltz, Bernardo RodrigueziturbeAbstract:BACKGROUND: Acute glomerulonephritis can follow infection by group A streptococci. An immune-complex pathogenesis is accepted, but the causative Antigen(s) is still controversial. In recent years, 2 streptococcal Antigens, the cationic cysteine proteinase exotoxin B (SPE B) and the plasmin receptor, a glyceraldehyde phosphate dehydrogenase (Plr, GAPDH) have attracted attention because: (1) they were localized in glomeruli in patients with acute post-streptococcal glomerulonephritis (APSGN); and (2) serum antibody to these Antigens was associated with Nephritogenic streptococcal infections. To date, putative nephritogens were always tested independently. Here, the relevance of SPE B and GAPDH was evaluated in the same renal biopsies and serum samples of well-defined APSGN patients. METHODS: Renal biopsies (17 patients) and serum samples (53 patients) with APSGN and appropriate controls were examined. Immunofluorescent staining of frozen sections was performed using specific antibodies to SPE B and GAPDH. Serum antibodies were investigated by both enzyme-linked immunosorbent assay (ELISA) and Western blot methodology. RESULTS: Glomerular deposits of SPE B were demonstrated in 12/17 APSGN biopsies, and 2 cases were borderline; circulating antibodies were found in all instances (53/53 patients). Glomerular deposition of GAPDH was detected in 1/17 biopsies, and 2 cases were borderline; circulating antibodies were found in 5/47 patients. In 31 control biopsies, only weak staining for each Antigen was found in 2 cases. CONCLUSION: In this study, glomerular deposits of and antibody response to zymogen/SPE B are more consistently present in APSGN than deposits and antibody response to GAPDH. Zymogen/SPE B is likely to be the major Antigen involved in the pathogenesis of most cases of APSGN.
Michael J. Mihatsch - One of the best experts on this subject based on the ideXlab platform.
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Is the Nephritogenic Antigen in post-streptococcal glomerulonephritis pyrogenic exotoxin B (SPE B) or GAPDH?
Kidney International, 2005Co-Authors: Stephen Batsford, Sergio Mezzano, Michael J. Mihatsch, Emile Schiltz, Bernardo Rodriguez-iturbeAbstract:Is the Nephritogenic Antigen in post-streptococcal glomerulonephritis pyrogenic exotoxin B (SPE B) or GAPDH? Background Acute glomerulonephritis can follow infection by group A streptococci. An immune-complex pathogenesis is accepted, but the causative Antigen(s) is still controversial. In recent years, 2 streptococcal Antigens, the cationic cysteine proteinase exotoxin B (SPE B) and the plasmin receptor, a glyceraldehyde phosphate dehydrogenase (Plr, GAPDH) have attracted attention because: ( 1 ) they were localized in glomeruli in patients with acute post-streptococcal glomerulonephritis (APSGN); and ( 2 ) serum antibody to these Antigens was associated with Nephritogenic streptococcal infections. To date, putative nephritogens were always tested independently. Here, the relevance of SPE B and GAPDH was evaluated in the same renal biopsies and serum samples of well-defined APSGN patients. Methods Renal biopsies (17 patients) and serum samples (53 patients) with APSGN and appropriate controls were examined. Immunofluorescent staining of frozen sections was performed using specific antibodies to SPE B and GAPDH. Serum antibodies were investigated by both enzyme-linked immunosorbent assay (ELISA) and Western blot methodology. Results Glomerular deposits of SPE B were demonstrated in 12/17 APSGN biopsies, and 2 cases were borderline; circulating antibodies were found in all instances (53/53 patients). Glomerular deposition of GAPDH was detected in 1/17 biopsies, and 2 cases were borderline; circulating antibodies were found in 5/47 patients. In 31 control biopsies, only weak staining for each Antigen was found in 2 cases. Conclusion In this study, glomerular deposits of and antibody response to zymogen/SPE B are more consistently present in APSGN than deposits and antibody response to GAPDH. Zymogen/SPE B is likely to be the major Antigen involved in the pathogenesis of most cases of APSGN.
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is the Nephritogenic Antigen in post streptococcal glomerulonephritis pyrogenic exotoxin b spe b or gapdh
Kidney International, 2005Co-Authors: Stephen Batsford, Sergio Mezzano, Michael J. Mihatsch, Emile Schiltz, Bernardo RodrigueziturbeAbstract:BACKGROUND: Acute glomerulonephritis can follow infection by group A streptococci. An immune-complex pathogenesis is accepted, but the causative Antigen(s) is still controversial. In recent years, 2 streptococcal Antigens, the cationic cysteine proteinase exotoxin B (SPE B) and the plasmin receptor, a glyceraldehyde phosphate dehydrogenase (Plr, GAPDH) have attracted attention because: (1) they were localized in glomeruli in patients with acute post-streptococcal glomerulonephritis (APSGN); and (2) serum antibody to these Antigens was associated with Nephritogenic streptococcal infections. To date, putative nephritogens were always tested independently. Here, the relevance of SPE B and GAPDH was evaluated in the same renal biopsies and serum samples of well-defined APSGN patients. METHODS: Renal biopsies (17 patients) and serum samples (53 patients) with APSGN and appropriate controls were examined. Immunofluorescent staining of frozen sections was performed using specific antibodies to SPE B and GAPDH. Serum antibodies were investigated by both enzyme-linked immunosorbent assay (ELISA) and Western blot methodology. RESULTS: Glomerular deposits of SPE B were demonstrated in 12/17 APSGN biopsies, and 2 cases were borderline; circulating antibodies were found in all instances (53/53 patients). Glomerular deposition of GAPDH was detected in 1/17 biopsies, and 2 cases were borderline; circulating antibodies were found in 5/47 patients. In 31 control biopsies, only weak staining for each Antigen was found in 2 cases. CONCLUSION: In this study, glomerular deposits of and antibody response to zymogen/SPE B are more consistently present in APSGN than deposits and antibody response to GAPDH. Zymogen/SPE B is likely to be the major Antigen involved in the pathogenesis of most cases of APSGN.