scholarly journals Impact of IgG Fc-fragments on experimental glomerulonephritis induced by Streptococcus pyogenes strain binding various immunoglobulin classes

2020 ◽  
Vol 10 (1) ◽  
pp. 55-63
Author(s):  
L. A. Burova ◽  
P. V. Pigarevsky ◽  
V. A. Snegova ◽  
A. A. Totolian
Keyword(s):  
Immune Complexes ◽  
Binding Proteins ◽  
Rabbit Model ◽  
Renal Tissue ◽  
Proliferative Glomerulonephritis ◽  
Pathological Changes ◽  
Experimental Glomerulonephritis ◽  
Rabbit Igg ◽  
Group A

The pathogenesis of poststreptococcal glomerulonephritis (PSGN), a major complication of acute infections caused by group A streptococci (GAS) remains unclear. Several theories, based on the role of certain streptococcal virulence factors, as well as immunological mimicry between GAS and renal tissue, have been proposed. Earlier, we reported that many virulent clinical GAS isolates showing confirmed nephritogenic activity were capable of nonimmune Fc binding of monomeric or aggregated IgG. Moreover, a rabbit model of PSGN allowed to obtain findings regarding a crucial role of streptococcal IgG Fc binding proteins belonging to the M family surface proteins, in the onset of PSGN. Rabbits injected with inactivated IgGFcBP-positive streptococci, acquired changes in the renal tissue with deposited IgG and complement C3, as well as signs of immune inflammation characteristic for human PSGN. Also, it was shown that the induction of experimental glomerulonephritis could be inhibited after normal IgG or its purified Fc fragments were inoculated at early stages of the process. The data obtained in rabbits injected with group A streptococcal type M60 also showed pathogenic functions of the IgA Fc-binding proteins of GAS. The aim of the study was to examine inhibiting activity of the purified rabbit IgG Fc fragments on the manifestations of glomerulonephritis induced by S. pyogenes strains capable of binding diverse forms of immunoglobulins such native IgG, immune complexes, and IgA.Materials and methods. GAS strains of emml, emml2 and emm60 genotypes were used to induce PSGN or IgA-nephropa-thy in rabbits. Fc fragments derived from rabbit IgG were obtained by enzymatic digestion and purified by affinity chromatography on a protein G-sepharose FF column. Immunomorphological changes of renal tissue were estimated by morphometric analysis.Results. In the present study, using the rabbit model, we revealed pathological changes of different intensity and localization in the renal tissue. For streptococci of the emm1 and emm12 genotypes, PSGN was characterized by deposition of IgG or IgG-anti-IgG immune complexes within the basal glomerular membrane. Morphological changes were evaluated as a membranous-proliferative glomerulonephritis. Meanwhile, IgA-glomerulonephritis is characterized by deposition of IgA in mesangial cells of glomeruli, leading to the mesangial-proliferative glomerulonephritis or IgA-nephropathy. Intravenously administered purified Fc fragments derived from normal rabbit IgG varied in effects on pathological processes: (i) IgG Fc fragments of fully inhibited development of the PSGN induced by IgG Fc binding strain of emml genotype, (ii) IgG Fc fragments of partially reverted changes caused by the emm12 genotype strain, which was binding only to immune complexes, and (iii) had no effects on pathological changes caused by the emm60 genotype GAS strain, which was binding only IgA.Conclusion. The data obtained point and emergence of differences in mechanisms of renal lesions development at glomerulonephritis, depending on the emm genotype of GAS strain. In addition, it also confirmed GAS-derived involvement for various IgFc-receptor proteins in the pathology. Further studies on potential prophylactic or curative effects of IgG Fc fragments in PSGN should therefore be of interest. The findings might suggest a new therapeutic approach for non-suppurative poststreptococcal diseases.

Immune complex binding Streptococcus pyogenes type M12/emm12 in experimental glomerulonephritis

2013 ◽  
Vol 62 (9) ◽  
pp. 1272-1280 ◽  
Author(s):  
Larissa Burova ◽  
Peter Pigarevsky ◽  
Nadezhda Duplik ◽  
Vlada Snegova ◽  
Alexander Suvorov ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Complement C3 ◽  
Poststreptococcal Glomerulonephritis ◽  
Tnf Α ◽  
Rabbit Igg ◽  
Renal Changes ◽  
Group A ◽  
Study Type ◽  
Binding Component

In a rabbit model, we have previously reported evidence for a pathogenic role of streptococcal IgG Fc-binding proteins (IgGFcBP) in poststreptococcal glomerulonephritis (PSGN). These proteins, of the M protein family, were shown to trigger anti-IgG production and enhance renal deposition of IgG and/or immune complexes (ICs), with resulting activation of complement and cytokine cascades. In the present study, type M12/emm12, group A streptococci (GAS) were found often to bind artificial ICs, viz. peroxidase–anti-peroxidase rabbit IgG (PAP) or tetanus toxoid–anti-tetanus human IgG (TAT), rather than monomeric IgG. Animals injected with each of four IC binding clinical isolates (from patients with scarlet fever or PSGN) showed pronounced inflammatory and degenerative glomerular changes, morphologically similar to human PSGN, with membrane thickening and IgG and complement C3 deposition, as well as secretion of IL-6 and TNF-α by mesangial and endothelial cells. In contrast, non-binding strains (two from asymptomatic carriers and one from a PSGN case) failed to trigger any renal changes. Only the IC binding strains induced elevated titres of anti-IgG. Though the streptococcal binding component(s) has not been demonstrated, the selective binding of ICs by type M12/emm12 strains appears important for the well-known, marked nephritogenic potential of this GAS type.

Role of group A streptococcal IgG-binding proteins in triggering experimental glomerulonephritis in the rabbit

Apmis ◽  
2003 ◽  
Vol 111 (10) ◽  
pp. 955-962 ◽  
Author(s):  
LARISSA BUROVA ◽  
ANETTE THERN ◽  
PITER PIGAREVSKY ◽  
MARIA GLADILINA ◽  
VALENTINA SELIVERSTOVA ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Experimental Glomerulonephritis ◽  
Igg Binding ◽  
Group A

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

2014 ◽  
Vol 14 (4-5) ◽  
pp. 383
Author(s):  
L. A. Burova ◽  
P. V. Pigarevsky ◽  
E. A. Gavrilova ◽  
V. G. Seliverstova ◽  
K. Schalen ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Group A Streptococcus ◽  
Experimental Glomerulonephritis ◽  
Group A

Proliferative glomerulonephritis

2020 ◽  
pp. 4933-4937
Author(s):  
Alan D. Salama ◽  
Mark A. Little
Keyword(s):  
Renal Function ◽  
Immune Complexes ◽  
Skin Infection ◽  
Mesangial Cells ◽  
Symptomatic Relief ◽  
Proliferative Glomerulonephritis ◽  
Complement Components ◽  
Poststreptococcal Glomerulonephritis ◽  
Histological Features ◽  
Group A

Proliferative glomerulonephritis describes the finding of increased cellularity of the glomerulus, which may be due to proliferation of intrinsic glomerular cells, infiltration of leucocytes, or both. This principally occurs in the context of glomerular deposition of immunoglobulins, immune complexes, or complement components. Different subtypes are described based on histological features: proliferation of mesangial cells, endocapillary proliferation, diffuse proliferation, or extracapillary proliferation (also termed crescentic glomerulonephritis). Patients will typically have haematuria, and this may be associated with proteinuria and/or impairment of excretory renal function and/or hypertension. The best characterized proliferative glomerulonephritis is poststreptococcal glomerulonephritis. This most commonly affects children, who present with nephritis about 2 weeks after pharyngitis or skin infection caused by streptococci of Lancefield group A. Treatment is directed at eradicating the infection with an appropriate antimicrobial and providing symptomatic relief. Recovery is the rule, although haematuria and proteinuria may persist.

Rabbit model of disseminated syphilis: immunoblot and immunohistologic evidence for a role of specific immune complexes in lesion pathogenesis

1988 ◽  
Vol 15 (3) ◽  
pp. 150-160 ◽  
Author(s):  
J. L. Jorizzo ◽  
M. C. McNeely ◽  
R. E. Baughn ◽  
T. Cavallo ◽  
A. R. Solomon ◽  
...  
Keyword(s):  
Immune Complexes ◽  
Rabbit Model

Etiology, clinical presentation, laboratory diagnostics, pathogenesis of impetigo and treatment methods

2020 ◽  
pp. 64-70
Author(s):  
Anastasiya Laknitskaya
Keyword(s):  
Streptococcus Pyogenes ◽  
Skin Diseases ◽  
Group A Streptococcus ◽  
Antibiotic Sensitivity ◽  
Antioxidant Defense System ◽  
Laboratory Diagnostics ◽  
Treatment Methods ◽  
Group A ◽  
The Individual

Currently, one of the priority medical and social problems is the optimization of treatment methods for pyoderma associated with Streptococcus pyogenes — group A streptococcus (GAS). To date, the proportion of pyoderma, the etiological factor of which is Streptococcus pyogenes, is about 6 % of all skin diseases and is in the range from 17.9 to 43.9 % of all dermatoses. Role of the bacterial factor in the development of streptococcal pyoderma is obvious. Traditional treatment complex includes antibacterial drugs selected individually, taking into account the antibiotic sensitivity of pathognomonic bacteria, and it is not always effective. Currently implemented immunocorrection methods often do not take into account specific immunological features of the disease, the individual, and the fact that the skin performs the function of not only a mechanical barrier, but it is also an immunocompetent organ. Such an approach makes it necessary to conduct additional studies clarifying the role of factors of innate and adaptive immunity, intercellular mediators and antioxidant defense system, that allow to optimize the treatment of this pathology.

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