scholarly journals The Role of Nephritis-Associated Plasmin Receptor (NAPlr) in Glomerulonephritis Associated with Streptococcal Infection

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Takashi Oda ◽  
Nobuyuki Yoshizawa ◽  
Kazuo Yamakami ◽  
Yutaka Sakurai ◽  
Hanako Takechi ◽  
...  
Keyword(s):  
Renal Biopsy ◽  
Streptococcal Infection ◽  
Group A Streptococcus ◽  
Plasmin Activity ◽  
Subsequent Formation ◽  
Poststreptococcal Glomerulonephritis ◽  
Circulating Antigen ◽  
Group A ◽  
Antigen Antibody

It is well known that glomerulonephritis can occur after streptococcal infection, which is classically referred to as acute poststreptococcal glomerulonephritis (APSGN). The pathogenic mechanism of APSGN has been described by so-called immune complex theory, which involves glomerular deposition of nephritogenic streptococcal antigen and subsequent formation of immune complexesin situand/or the deposition of circulating antigen-antibody complexes. However, the exact entity of the causative antigen has remained a matter of debate. We isolated a nephritogenic antigen for APSGN from the cytoplasmic fractions of group A streptococcus (GAS) depending on the affinity for IgG of APSGN patients. The amino acid and the nucleotide sequences of the isolated protein revealed to be highly identical to those of reported plasmin(ogen) receptor of GAS. Thus, we termed this antigen nephritis-associated plasmin receptor (NAPlr). Immunofluorescence staining of the renal biopsy tissues with anti-NAPlr antibody revealed glomerular NAPlr deposition in essentially all patients with early-phase APSGN. Furthermore, glomerular plasmin activity was detected byin situzymography in the distribution almost identical to NAPlr deposition in renal biopsy tissues of APSGN patients. These data suggest that NAPlr has a direct, nonimmunologic function as a plasmin receptor and may contribute to the pathogenesis of APSGN by maintaining plasmin activity.

scholarly journals Glomerular Deposition of Nephritis-Associated Plasmin Receptor (NAPlr) and Related Plasmin Activity: Key Diagnostic Biomarkers of Bacterial Infection-related Glomerulonephritis

2020 ◽  
Vol 21 (7) ◽  
pp. 2595 ◽  
Author(s):  
Takahiro Uchida ◽  
Takashi Oda
Keyword(s):  
Streptococcal Infection ◽  
Group A Streptococcus ◽  
Acute Glomerulonephritis ◽  
Similar Distribution ◽  
Plasmin Activity ◽  
Glomerular Diseases ◽  
Diagnostic Biomarkers ◽  
Group A ◽  
Poststreptococcal Acute Glomerulonephritis ◽  
Similar Distribution Pattern

It is widely known that glomerulonephritis (GN) often develops after the curing of an infection, a typical example of which is GN in children following streptococcal infections (poststreptococcal acute glomerulonephritis; PSAGN). On the other hand, the term “infection-related glomerulonephritis (IRGN)” has recently been proposed, because infections are usually ongoing at the time of GN onset in adult patients, particularly in older patients with comorbidities. However, there has been no specific diagnostic biomarker for IRGN, and diagnosis is based on the collection of several clinical and pathological findings and the exclusion of differential diagnoses. Nephritis-associated plasmin receptor (NAPlr) was originally isolated from the cytoplasmic fraction of group A streptococcus as a candidate nephritogenic protein for PSAGN and was found to be the same molecule as streptococcal glyceraldehyde-3-phosphate dehydrogenase and plasmin receptor. NAPlr deposition and related plasmin activity were observed with a similar distribution pattern in the glomeruli of patients with PSAGN. However, glomerular NAPlr deposition and plasmin activity could be observed not only in patients with PSAGN but also in patients with other glomerular diseases, in whom a preceding streptococcal infection was suggested. Furthermore, such glomerular staining patterns have been demonstrated in patients with IRGN induced by bacteria other than streptococci. This review discusses the recent advances in our understanding of the pathogenesis of bacterial IRGN, which is characterized by NAPlr and plasmin as key biomarkers.

RECOVERY FROM RENAL FAILURE DUE TO ACUTE DIFFUSE INTERSTITIAL NEPHRITIS

PEDIATRICS ◽  
1969 ◽  
Vol 43 (4) ◽  
pp. 533-539 ◽  
Author(s):  
James H. Knepshield ◽  
Per Henrik Becher Carstens ◽  
Dominick E. Gentile
Keyword(s):  
Renal Failure ◽  
Renal Biopsy ◽  
Interstitial Nephritis ◽  
Cellular Response ◽  
Streptococcal Infection ◽  
Tubular Basement Membrane ◽  
Tubular Necrosis ◽  
Oliguric Renal Failure ◽  
Group A ◽  
Antigen Antibody

A 3-year-old girl developed acute oliguric renal failure and Coombs' positive hemolytic anemia during the course of a Group A, β-hemolytic streptococcal infection. Renal biopsy established the diagnosis of acute diffuse interstitial nephritis (ADIN) in combination with tubular necrosis. Electron microscopy of the biopsy specimen confirmed the finding of tubular necrosis and revealed focal areas of dilatation of the basal infoldings from the plasma membrane. The tubular basement membrane was fragmented. Peritoneal dialysis and other supportive measures sustained the patient until adequate renal function returned. To our knowledge, this patient represents the first reported case of recovery from ADIN associated with a streptococcal infection. The latent period between the onset of the infection and the renal manifestations, and the nature of the cellular response seen in the renal biopsy suggest an antigen-antibody reaction as the cause of the renal injury. The cause of oliguria in ADIN remains obscure. However, tubular necrosis is a well-known cause of acute oliguric renal failure and this lesion probably plays a role in the functional impairment of ADIN.

Immunopathological mechanisms in bacterial-host interactions

1983 ◽  
Vol 303 (1114) ◽  
pp. 177-187 ◽  
Keyword(s):  
Rheumatic Fever ◽  
Group A Streptococcus ◽  
Biological Properties ◽  
Antigenic Determinants ◽  
Bacterial Host ◽  
Poststreptococcal Glomerulonephritis ◽  
Host Interactions ◽  
Disease States ◽  
Group A ◽  
Specific Tissue

The ability of bacteria to cause immunopathological damage in the host may take a variety of forms. These pathways may be conveniently grouped under three major headings: (1) organisms that can cause damage via shared antigenic determinants between host and bacterium; (2) those organisms that suppress the host’s response; and (3) organisms that release substances with specific biological properties or have receptors for specific tissue sites. The group A streptococcus is among the most versatile of these bacteria because it appears that it may use all three pathways in various streptococcal-related disease states. In rheumatic fever and chorea it appears that cross-reactive antigens play a major role in inducing immunopathological damage in that there is both a heightened humoral and cellular reaction by the host to these cross-reactive determinants. Recent evidence also indicates that rheumatic fever individuals express certain B cell antigens that may be associated with susceptibility to the disease. In the other complications of streptococcal infections, namely poststreptococcal glomerulonephritis, the bacterium uses both suppression of the host’s immune response and the excretion of a particular protein common to all nephritis-associated strains to achieve its immunopathological damage. In this context, other examples of bacterial-host interactions will be discussed as evidence for the common pathways used by microbes to cause immunopathological damage in the host.

scholarly journals Characterization of Biofilm Formation by Clinically Relevant Serotypes of Group A Streptococci

2006 ◽  
Vol 72 (4) ◽  
pp. 2864-2875 ◽  
Author(s):  
Cordula Lembke ◽  
Andreas Podbielski ◽  
Carlos Hidalgo-Grass ◽  
Ludwig Jonas ◽  
Emanuel Hanski ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Laser Scanning ◽  
Group A Streptococcus ◽  
Three Dimensional ◽  
Positive Control ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Subsequent Formation ◽  
Group A

ABSTRACT Streptococcus pyogenes (group A streptococcus [GAS]) is a frequent cause of purulent infections in humans. As potentially important aspects of its pathogenicity, GAS was recently shown to aggregate, form intratissue microcolonies, and potentially participate in multispecies biofilms. In this study, we show that GAS in fact forms monospecies biofilms in vitro, and we analyze the basic parameters of S. pyogenes in vitro biofilm formation, using Streptococcus epidermidis as a biofilm-positive control. Of nine clinically important serotype strains, M2, M6, M14, and M18 were found to significantly adhere to coated and uncoated polystyrene surfaces. Fibronectin and collagen types I and IV best supported primary adherence of serotype M2 and M18 strains, respectively, whereas serotype M6 and M14 strains strongly bound to uncoated polystyrene surfaces. Absorption measurements of safranin staining, as well as electron scanning and confocal laser scanning microscopy, documented that primary adherence led to subsequent formation of three-dimensional biofilm structures consisting of up to 46 bacterial layers. Of note, GAS isolates belonging to the same serotype were found to be very heterogeneous in their biofilm-forming behavior. Biofilm formation was equally efficient under static and continuous flow conditions and consisted of the classical three steps, including partial disintegration after long-term incubation. Activity of the SilC signaling peptide as a component of a putative quorum-sensing system was found to influence the biofilm structure and density of serotype M14 and M18 strains. Based on the presented methods and results, standardized analyses of GAS biofilms and their impact on GAS pathogenicity are now feasible.

Poststreptococcal Movement Disorders

2017 ◽  
Author(s):  
Davide Martino ◽  
Gavin Giovannoni
Keyword(s):  
Movement Disorders ◽  
Streptococcal Infection ◽  
Group A Streptococcus ◽  
Neuropsychiatric Symptoms ◽  
Causal Link ◽  
Obsessive Compulsive ◽  
Behavioral Abnormalities ◽  
Group A ◽  
Obsessive Compulsive Disorders ◽  
Compulsive Disorders

The spectrum of “poststreptococcal” movement disorders and other behavioral abnormalities has expaanded and the array of neuropsychiatric features associated with rheumatic fever (RF) has been broadened. However, it is difficult to establish a causal link between Group A Streptococcus (GAS) and neuropsychiatric symptoms beyond RF, which has fuelled a long-lasting, and still unsolved, debate as to whether putative “poststreptococcal” disorders such as the PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection) phenotype are distinct entities or not. This chapter provides an up-to-date overview of the conditions that are well established (Sydenham’s chorea) or proposed (poststreptococcal tic and obsessive-compulsive disorders) as secondary to an immune response toward GAS.

Streptococcal Submandibular Cellulitis in Young Infants

PEDIATRICS ◽  
1981 ◽  
Vol 67 (3) ◽  
pp. 378-380 ◽  
Author(s):  
Pisespong Patamasucon ◽  
Jane D. Siegel ◽  
George H. McCracken
Keyword(s):  
Clinical Presentation ◽  
Streptococcal Infection ◽  
Group A Streptococcus ◽  
Hemolytic Streptococcus ◽  
Young Infants ◽  
Group A ◽  
Ludwig’S Angina ◽  
Group B ◽  
Ludwig's Angina

Six infants with streptococcal submandibular cellulitis and bacteremia were managed in our institution during a seven-month period. Five uncomplicated cases were caused by group B β-hemolytic Streptococcus, and one rapidly progressive case of Ludwig's angina was caused by group A Streptococcus. Recognition of this characteristic clinical presentation of group B streptococcal infection may be beneficial in the management of such patients.

scholarly journals Paediatric Autoimmune Neuropsychiatric Disorder Associated with Group A Beta-Haemolytic Streptococcal Infection: An Indication for Tonsillectomy? A Review of the Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Amarkumar Dhirajlal Rajgor ◽  
Navid Akhtar Hakim ◽  
Sanah Ali ◽  
Adnan Darr
Keyword(s):  
Streptococcal Infection ◽  
Group A Streptococcus ◽  
Case Reports ◽  
Neuropsychiatric Symptoms ◽  
Case Series ◽  
Acute Onset ◽  
Neuropsychiatric Disorder ◽  
Inclusion Criteria ◽  
Definitive Evidence ◽  
Group A

Background. Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection (PANDAS) is the acute onset of neuropsychiatric symptoms following group A beta-haemolytic streptococcal infection. The aetiology remains elusive. However, with group A streptococcus being the most common bacterial cause of tonsillitis, surgical intervention in the form of tonsillectomy has often been considered as a potential therapy. Methods. A MEDLINE® search was undertaken using keywords “PANDAS” or “paediatric autoimmune neuropsychiatric disorders associated with streptococcus” combined with “tonsillectomy”. Results. Six case reports and 3 case series met the inclusion criteria. Demesh et al. (case series) reported a dramatic reduction in neuropsychiatric symptom severity in the patient cohort undergoing tonsillectomy. Two case series suggest that there is no association between tonsillectomy and resolution of PANDAS. Conclusion. Due to the lack of uniform data and sporadic reports, tonsillectomy should be carefully adopted for the treatment of this disorder. In particular, tonsillectomies/adenoidectomies to alleviate neuropsychiatric symptoms should be avoided until more definitive evidence is at our disposal. This review highlights the importance of a potential collaborative prospective study.

scholarly journals A brief review on Group A Streptococcus pathogenesis and vaccine development

2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Sowmya Ajay Castro ◽  
Helge C. Dorfmueller
Keyword(s):  
Rheumatic Fever ◽  
Prolonged Exposure ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Streptococcal Toxic Shock Syndrome ◽  
Host Immune System ◽  
Industrialized Countries ◽  
Poststreptococcal Glomerulonephritis ◽  
Group A ◽  
The Impact

Streptococcus pyogenes , also known as Group A Streptococcus (GAS), is a Gram-positive human-exclusive pathogen, responsible for more than 500 000 deaths annually worldwide. Upon infection, GAS commonly triggers mild symptoms such as pharyngitis, pyoderma and fever. However, recurrent infections or prolonged exposure to GAS might lead to life-threatening conditions. Necrotizing fasciitis, streptococcal toxic shock syndrome and post-immune mediated diseases, such as poststreptococcal glomerulonephritis, acute rheumatic fever and rheumatic heart disease, contribute to very high mortality rates in non-industrialized countries. Though an initial reduction in GAS infections was observed in high-income countries, global outbreaks of GAS, causing rheumatic fever and acute poststreptococcal glomerulonephritis, have been reported over the last decade. At the same time, our understanding of GAS pathogenesis and transmission has vastly increased, with detailed insight into the various stages of infection, beginning with adhesion, colonization and evasion of the host immune system. Despite deeper knowledge of the impact of GAS on the human body, the development of a successful vaccine for prophylaxis of GAS remains outstanding. In this review, we discuss the challenges involved in identifying a universal GAS vaccine and describe several potential vaccine candidates that we believe warrant pursuit.

scholarly journals Group A Streptococcus-Induced Activation of Human Plasminogen Is Required for Keratinocyte Wound Retraction and Rapid Clot Dissolution

2021 ◽  
Vol 8 ◽  
Author(s):  
Henry M. Vu ◽  
Daniel E. Hammers ◽  
Zhong Liang ◽  
Gabrielle L. Nguyen ◽  
Mary E. Benz ◽  
...  
Keyword(s):  
Time Course ◽  
Group A Streptococcus ◽  
Critical Role ◽  
Leading Edge ◽  
Fibrin Clot ◽  
Wound Site ◽  
Rapid Dissolution ◽  
Group A ◽  
Human Plasminogen

Invasive outcomes of Group A Streptococcus (GAS) infections that involve damage to skin and other tissues are initiated when these bacteria colonize and disseminate via an open wound to gain access to blood and deeper tissues. Two critical GAS virulence factors, Plasminogen-Associated M-Protein (PAM) and streptokinase (SK), work in concert to bind and activate host human plasminogen (hPg) in order to create a localized proteolytic environment that alters wound-site architecture. Using a wound scratch assay with immortalized epithelial cells, real-time live imaging (RTLI) was used to examine dynamic effects of hPg activation by a PAM-containing skin-trophic GAS isolate (AP53R+S−) during the course of infection. RTLI of these wound models revealed that retraction of the epithelial wound required both GAS and hPg. Isogenic AP53R+S− mutants lacking SK or PAM highly attenuated the time course of retraction of the keratinocyte wound. We also found that relocalization of integrin β1 from the membrane to the cytoplasm occurred during the wound retraction event. We devised a combined in situ-based cellular model of fibrin clot-in epithelial wound to visualize the progress of GAS pathogenesis by RTLI. Our findings showed GAS AP53R+S− hierarchically dissolved the fibrin clot prior to the retraction of keratinocyte monolayers at the leading edge of the wound. Overall, our studies reveal that localized activation of hPg by AP53R+S−via SK and PAM during infection plays a critical role in dissemination of bacteria at the wound site through both rapid dissolution of the fibrin clot and retraction of the keratinocyte wound layer.

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