PURIFIED IGG F C-BINDING PROTEINS FROM M22 GROUP A STREPTOCOCCUS ARE ABLE TO INDUCE EXPERIMENTAL GLOMERULONEPHRITIS

Abstract. Pathogenesis of acute post-streptococcal glomerulonephritis (APSGN), a major complication of group A streptococcal (GAS) throat or skin disease, remains unclear. Over years, various theories were based on distinct streptococcal extracellular factors, as well as immunological mimicry of str...

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Main Authors: L. A. Burova, P. V. Pigarevsky, E. A. Gavrilova, V. G. Seliverstova, K. Schalen, Artem A. Totolyan, T. V. Gupalova
Format: Article
Language:Russian
Published: St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists 2014-07-01
Series:Медицинская иммунология
Subjects:
Online Access:https://www.mimmun.ru/mimmun/article/view/460
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author L. A. Burova
P. V. Pigarevsky
E. A. Gavrilova
V. G. Seliverstova
K. Schalen
Artem A. Totolyan
T. V. Gupalova
author_facet L. A. Burova
P. V. Pigarevsky
E. A. Gavrilova
V. G. Seliverstova
K. Schalen
Artem A. Totolyan
T. V. Gupalova
author_sort L. A. Burova
collection DOAJ
description Abstract. Pathogenesis of acute post-streptococcal glomerulonephritis (APSGN), a major complication of group A streptococcal (GAS) throat or skin disease, remains unclear. Over years, various theories were based on distinct streptococcal extracellular factors, as well as immunological mimicry of streptococci for renal tissue antigens was considered. Previously we reported that a lot of clinical GAS isolates with proven nephritogenic ability show a non-immune binding of monomeric or aggregated IgG. Moreover, using a rabbit model of APSGN, we obtained evidence for important causative role of streptococcal IgG Fc-binding proteins (IgG FcBPs) belonging to the M family surface proteins. I.e., rabbits injected by whole IgG FcBP-positive streptococci showed induction of renal glomerular changes, with deposition of IgG and complement C3, resembling the picture recorded in human APSGN. These typical renal changes were always preceded by development of circulating anti-IgG antibodies. Present study was performed in the same rabbit model. Both purified IgG FcBPs isolated from type M22 GAS were found to elicit glomerular degenerative damage of renal glomeruli comparable to those caused by whole bacteria, as well as induce anti-IgG antibodies, deposition of IgG and C3 complement and production of proinflammatory cytokines (IL-1β, TNFα, IL-6) by glomerular mesangial and endothelial cells. By contrast, rabbits injected with proteins A or G, IgG FcBPs of S. aureus and group G streptococci, respectively, exhibited only low levels of circulating anti-IgG and reversible glomerular changes. In these settings, we have not observed any features of membranousproliferative glomerulonephritis (GN) resembling morphological traits of acute post-streptococcal GN in humans. These data correlated with results obtained after injection of intact Staphylococcus aureus (Cowan 1 strain) or group G streptococci (G148 strain). Both microbial types are known to harbor IgG Fc-binding proteins (А and G, respectively). These results support the idea that GAS IgG FcBPs are unique in their ability to initiate strong post-streptococcal glomerular changes and could be considered as important factors in pathogenesis of APSGN similar to acute post-streptococcal GN in humans.
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spelling doaj.art-8101022437ba46e391df35c633d9be652024-04-22T13:07:36ZrusSt. Petersburg branch of the Russian Association of Allergologists and Clinical ImmunologistsМедицинская иммунология1563-06252313-741X2014-07-01144-538339010.15789/1563-0625-2012-4-5-383-390457PURIFIED IGG F C-BINDING PROTEINS FROM M22 GROUP A STREPTOCOCCUS ARE ABLE TO INDUCE EXPERIMENTAL GLOMERULONEPHRITISL. A. Burova0P. V. Pigarevsky1E. A. Gavrilova2V. G. Seliverstova3K. Schalen4Artem A. Totolyan5T. V. Gupalova6ФГБУ Научно-исследовательский институт экспериментальной медицины Северо-Западного отделения РАМН, Санкт-ПетербургФГБУ Научно-исследовательский институт экспериментальной медицины Северо-Западного отделения РАМН, Санкт-ПетербургФГБУ Научно-исследовательский институт экспериментальной медицины Северо-Западного отделения РАМН, Санкт-ПетербургФГБУ Научно-исследовательский институт экспериментальной медицины Северо-Западного отделения РАМН, Санкт-ПетербургФГБУ Научно-исследовательский институт экспериментальной медицины Северо-Западного отделения РАМН, Санкт-ПетербургОтдел лабораторной медицины Лундского Университета, Лунд, ШвецияФГБУ Научно-исследовательский институт экспериментальной медицины Северо-Западного отделения РАМН, Санкт-ПетербургAbstract. Pathogenesis of acute post-streptococcal glomerulonephritis (APSGN), a major complication of group A streptococcal (GAS) throat or skin disease, remains unclear. Over years, various theories were based on distinct streptococcal extracellular factors, as well as immunological mimicry of streptococci for renal tissue antigens was considered. Previously we reported that a lot of clinical GAS isolates with proven nephritogenic ability show a non-immune binding of monomeric or aggregated IgG. Moreover, using a rabbit model of APSGN, we obtained evidence for important causative role of streptococcal IgG Fc-binding proteins (IgG FcBPs) belonging to the M family surface proteins. I.e., rabbits injected by whole IgG FcBP-positive streptococci showed induction of renal glomerular changes, with deposition of IgG and complement C3, resembling the picture recorded in human APSGN. These typical renal changes were always preceded by development of circulating anti-IgG antibodies. Present study was performed in the same rabbit model. Both purified IgG FcBPs isolated from type M22 GAS were found to elicit glomerular degenerative damage of renal glomeruli comparable to those caused by whole bacteria, as well as induce anti-IgG antibodies, deposition of IgG and C3 complement and production of proinflammatory cytokines (IL-1β, TNFα, IL-6) by glomerular mesangial and endothelial cells. By contrast, rabbits injected with proteins A or G, IgG FcBPs of S. aureus and group G streptococci, respectively, exhibited only low levels of circulating anti-IgG and reversible glomerular changes. In these settings, we have not observed any features of membranousproliferative glomerulonephritis (GN) resembling morphological traits of acute post-streptococcal GN in humans. These data correlated with results obtained after injection of intact Staphylococcus aureus (Cowan 1 strain) or group G streptococci (G148 strain). Both microbial types are known to harbor IgG Fc-binding proteins (А and G, respectively). These results support the idea that GAS IgG FcBPs are unique in their ability to initiate strong post-streptococcal glomerular changes and could be considered as important factors in pathogenesis of APSGN similar to acute post-streptococcal GN in humans.https://www.mimmun.ru/mimmun/article/view/460m22 group a streptococcusisogenic mutantspurified igg fc-binding proteinsexperimental glomerulonephritis
spellingShingle L. A. Burova
P. V. Pigarevsky
E. A. Gavrilova
V. G. Seliverstova
K. Schalen
Artem A. Totolyan
T. V. Gupalova
PURIFIED IGG F C-BINDING PROTEINS FROM M22 GROUP A STREPTOCOCCUS ARE ABLE TO INDUCE EXPERIMENTAL GLOMERULONEPHRITIS
Медицинская иммунология
m22 group a streptococcus
isogenic mutants
purified igg fc-binding proteins
experimental glomerulonephritis
title PURIFIED IGG F C-BINDING PROTEINS FROM M22 GROUP A STREPTOCOCCUS ARE ABLE TO INDUCE EXPERIMENTAL GLOMERULONEPHRITIS
title_full PURIFIED IGG F C-BINDING PROTEINS FROM M22 GROUP A STREPTOCOCCUS ARE ABLE TO INDUCE EXPERIMENTAL GLOMERULONEPHRITIS
title_fullStr PURIFIED IGG F C-BINDING PROTEINS FROM M22 GROUP A STREPTOCOCCUS ARE ABLE TO INDUCE EXPERIMENTAL GLOMERULONEPHRITIS
title_full_unstemmed PURIFIED IGG F C-BINDING PROTEINS FROM M22 GROUP A STREPTOCOCCUS ARE ABLE TO INDUCE EXPERIMENTAL GLOMERULONEPHRITIS
title_short PURIFIED IGG F C-BINDING PROTEINS FROM M22 GROUP A STREPTOCOCCUS ARE ABLE TO INDUCE EXPERIMENTAL GLOMERULONEPHRITIS
title_sort purified igg f c binding proteins from m22 group a streptococcus are able to induce experimental glomerulonephritis
topic m22 group a streptococcus
isogenic mutants
purified igg fc-binding proteins
experimental glomerulonephritis
url https://www.mimmun.ru/mimmun/article/view/460
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