Staphylococcus aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy

Kôyama, Akio; Sharmin, Samina; Sakurai, Hideko; Shimizu, Yoshio; Hirayama, Kouichi; Usui, Joichi; Nagata, Michio; Yoh, Keigyou; Yamagata, Kunihiro; Muro, Kaori; Kobayashi, Masaki; Ohtani, Kaori; Shimizu, Takeshi; Shimizu, Tohru

doi:10.1111/j.1523-1755.2004.00714.x

Cited by 108 publications

(62 citation statements)

References 32 publications

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“…Koyoma and coworkers (2,9) indicate the role of Staphylococcus superantigens in the pathogenesis. Staphylococcal enterotoxins may behave as superantigens that can bind directly to major histocompatibility complex (MHC) class II molecules on antigen-presenting cells.…”

Section: Discussionmentioning

confidence: 99%

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Staphylococcus Infection-Associated Glomerulonephritis Mimicking IgA Nephropathy

Satoskar

Nadasdy

Plaza

et al. 2006

Clinical Journal of the American Society of Nephrology

133

152

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The association of methicillin-resistant Staphylococcus aureus (MRSA) infection with glomerulonephritis (GN) has been well documented in Japan but not in North America. Recently, eight renal biopsies with IgA-predominant or -codominant GN from eight patients with underlying staphylococcal infection, but without endocarditis, were observed at a single institution in a 12-mo period. Renal biopsies were worked up by routinely used methodologies. Eight cases of primary IgA nephropathy were used as controls. Five patients had MRSA infection, one had methicillin-resistant S. epidermidis (MRSE) infection, and two had methicillin-sensitive S. aureus infection. Four patients became infected after surgery; two patients were diabetic and had infected leg ulcers. All patients developed acute renal failure, with active urine sediment and severe proteinuria. Most renal biopsies showed only mild glomerular hypercellularity. Two biopsies had prominent mesangial and intracapillary hypercellularity; one of them (the MRSE-associated case) had large glomerular hyalin thrombi. This patient also had a positive cryoglobulin test. Rare glomerular hyalin thrombi were noted in two other cases. Immunofluorescence showed IgA pre-or codominance in all biopsies. Electron microscopy revealed mesangial deposits in all cases. Five biopsies had rare glomerular capillary deposits as well. In the MRSE-associated GN, large subendothelial electron-dense deposits were present. These cases demonstrate that staphylococcal (especially MRSA) infection-associated GN occurs in the US as well, and a rising incidence is possible. It is important to differentiate a Staphylococcus infection-associated GN from primary IgA nephropathy to avoid erroneous treatment with immunosuppressive medications.Clin J Am Soc Nephrol 1: 1179 -1186, 2006. doi: 10.2215/CJN.01030306 S taphylococci are widespread pathogens and their frequent antibiotic resistance makes treatment difficult. Occasional episodes of glomerulonephritis (GN) after Staphylococcus epidermidis bacteremia in patients with ventriculoatrial or ventriculojugular shunts and after S. aureus bacteriemia secondary to endocarditis are well documented and are discussed in most nephrology and renal pathology textbooks. These Staphylococcus infection-related glomerulonephritides are associated with glomerular immune complex deposits, which contain complement (mainly C3) IgG and sometimes IgM. Much less is known about GN associated with methicillinresistant S. aureus (MRSA), and methicillin-resistant S. epidermidis (MRSE), which are now endemic in most hospitals. A growing number of community-acquired infections are also reported (1).The association of MRSA infection with GN has been well documented in Japan (2-9). Based primarily on these publications, it appears evident that S. aureus-associated GN is characterized by glomerular IgA deposits; therefore, the renal biopsy findings strongly resemble primary (idiopathic) IgA nephropathy. The IgA-containing immune complexes are mainly deposited in the mesangium, but they ...

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Section: Discussionmentioning

confidence: 99%

“…The association of MRSA infection with GN has been well documented in Japan (2)(3)(4)(5)(6)(7)(8)(9). Based primarily on these publications, it appears evident that S. aureus-associated GN is characterized by glomerular IgA deposits; therefore, the renal biopsy findings strongly resemble primary (idiopathic) IgA nephropathy.…”

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confidence: 99%

Staphylococcus Infection-Associated Glomerulonephritis Mimicking IgA Nephropathy

Satoskar

Nadasdy

Plaza

et al. 2006

Clinical Journal of the American Society of Nephrology

133

152

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“…These workers further showed that S. aureus cell envelope antigen was colocalized with IgA antibody in the glomeruli and suggested that S. aureus cell envelope antigen was a candidate for the induction of IgA nephropathy. 15 Regarding non-staphylococcal pathogens, Endo et al 16 demonstrated that various strains of gram-negative bacteria cell wall components, including Pseudomonas aeruginosa, E. coli, Haemophilus influenzae, and K. pneumoniae, can induce glomerular deposition of IgA and C3 in animal studies.…”

Section: Discussionmentioning

confidence: 99%

IgA-Dominant Postinfectious Glomerulonephritis: Not Peculiar to Staphylococcal Infection and Diabetic Patients

Wen

Chen

2011

Renal Failure

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Background: IgA-dominant postinfectious glomerulonephritis (PIGN) is a unique form of PIGN. It has been linked to staphylococcal infection and underlying diabetic glomerulosclerosis. However, the significance of glomerular IgA-dominant deposition in PIGN remains unclear. Methods: We reported 10 patients with IgA-dominant PIGN encountered at a single center, each characterized by subepithelial humps. Their demographic, clinical, and renal biopsy findings were summarized and compared with the data of 32 patients with non-IgA-dominant PIGN. Results: The mean age was 57 years. An immunocompromised background was present in 70% of patients; only one patient had diabetes mellitus. The causative infectious agents included Staphylococcus (30%), Streptococcus (20%), and gram-negative organisms (50%). Decreased serum complement was present in 60%. Increased serum IgA was noted in 75%. The mean peak serum creatinine was 5.1 mg/dL, and 20% required acute dialysis. Diffuse endocapillary-proliferative glomerulonephritis was found in all cases, and three patients also had crescentic glomerulonephritis. Electron microscopy revealed large subepithelial hump-shaped deposits in all cases. At the last follow-up, one patient had died, five had achieved complete recovery, three had persistent renal insufficiency, and one was on chronic dialysis. Compared to patients with non-IgA-dominant PIGN, increased serum IgA was more commonly present in IgA-dominant group ( p = 0.007). There were no significant differences in other clinical parameters and outcome between the two groups. Conclusions: IgA-dominant PIGN resembles poststreptococcal glomerulonephritis in its histological spectrum and ultrastructural appearance. Increasing serum IgA may be involved in the pathogenesis of this form of PIGN. Our data suggested that IgA-dominant PIGN was not peculiar to staphylococcal infection and diabetic patients.

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“…For example, in a Japanese study, 68% of renal biopsy specimens from patients with IgA nephropathy, an envelope antigen of Staphylococcus aureus, was co-localized with an IgA antibody in glomeruli (27). In Wegener's granulomatosis, respiratory tract infections frequently precede or accompany initial symptoms of upper airway involvement (3).…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Upregulates Toll-Like Receptor 4 on Mesangial Cells

Wolf

Bohlender²,

Bondeva³

et al. 2006

Journal of the American Society of Nephrology

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Angiotensin II (AngII) mediates proinflammatory properties by activating NF-B transcription factor nuclear translocation and inducing the expression of chemokines. For examination of whether AngII modulates the expression of Toll-like receptor 4 (TLR4), a key element of the innate immune system that senses LPS, mouse mesangial cells (MMC) were treated with AngII. AngII upregulated TLR4 mRNA and protein in MMC, and this effect was mediated through AngII type 1 receptors. Reporter gene experiments indicate that an activating protein-1 (AP-1) as well as an E-26 specific sequence (Ets) binding site in the TLR4 promoter are responsible for the AngII-stimulated transcriptional activity of the TLR4 gene. Preincubation of MMC with AngII enhanced LPS-induced NF-B activation and chemokine expression. Immunohistochemical analyses revealed that double-transgenic rats that overexpressed human renin and angiotensinogen expressed higher levels of glomerular TLR4 compared with normal Sprague-Dawley rats. In vivo, infusion with AngII but not with norepinephrine into rats for 7 d also enhanced glomerular NF-B activation after systemic application of LPS, suggesting that the effects are independent of concomitantly induced hypertension. Together, these observations suggest that AngII leads to an activation of the innate immune system by a novel mechanism involving the upregulation of TLR4. Our data contribute to a better understanding of how exogenous infections may trigger renal autoimmune processes, particularly in pathophysiologic situations with high renal AngII concentrations. Because TLR4 binds endogenous ligands (e.g., extracellular matrix components) in addition to microbial products, AngII-mediated upregulation of TLR4 also could be relevant for the development of inflammation in many noninfectious renal diseases.

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Staphylococcus aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy

Abstract: S. aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy.

Cited by 108 publications

References 32 publications

Staphylococcus Infection-Associated Glomerulonephritis Mimicking IgA Nephropathy

Staphylococcus Infection-Associated Glomerulonephritis Mimicking IgA Nephropathy

IgA-Dominant Postinfectious Glomerulonephritis: Not Peculiar to Staphylococcal Infection and Diabetic Patients

Angiotensin II Upregulates Toll-Like Receptor 4 on Mesangial Cells

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