Differences in verotoxin neutralizing activity of therapeutic immunoglobulins and sera from healthy controls

Bitzan, Martin; Klemt, M.; Steffens, R.; Müller‐Wiefel, D. E.

doi:10.1007/bf01710530

Cited by 32 publications

(15 citation statements)

References 46 publications

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“…It has been suggested that neurological involvement may be due to deficiency or impaired function of an Stx2-neutralizing factor (13) in affected patients, in which case plasma supply and exchange might be beneficial. Various candidates for such a neutralizing factor have been investigated, and serum amyloid P component (SAP) appears to be the most promising (14,15).…”

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confidence: 99%

Protection of Human Podocytes from Shiga Toxin 2-Induced Phosphorylation of Mitogen-Activated Protein Kinases and Apoptosis by Human Serum Amyloid P Component

et al. 2014

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jHemolytic uremic syndrome (HUS) is mainly induced by Shiga toxin 2 (Stx2)-producing Escherichia coli. Proteinuria can occur in the early phase of the disease, and its persistence determines the renal prognosis. Stx2 may injure podocytes and induce proteinuria. Human serum amyloid P component (SAP), a member of the pentraxin family, has been shown to protect against Stx2-induced lethality in mice in vivo, presumably by specific binding to the toxin. We therefore tested the hypothesis that SAP can protect against Stx2-induced injury of human podocytes. To elucidate the mechanisms underlying podocyte injury in HUS-associated proteinuria, we assessed Stx2-induced activation of mitogen-activated protein kinases (MAPKs) and apoptosis in immortalized human podocytes and evaluated the impact of SAP on Stx2-induced damage. Human podocytes express Stx2-binding globotriaosylceramide 3. Stx2 applied to cultured podocytes was internalized and then activated p38␣ MAPK and c-Jun N-terminal kinase (JNK), important signaling steps in cell differentiation and apoptosis. Stx2 also activated caspase 3, resulting in an increased level of apoptosis. Coincubation of podocytes with SAP and Stx2 mitigated the effects of Stx2 and induced upregulation of antiapoptotic Bcl2. These data suggest that podocytes are a target of Stx2 and that SAP protects podocytes against Stx2-induced injury. SAP may therefore be a useful therapeutic option.

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confidence: 99%

Protection of Human Podocytes from Shiga Toxin 2-Induced Phosphorylation of Mitogen-Activated Protein Kinases and Apoptosis by Human Serum Amyloid P Component

et al. 2014

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“…As in many toxin-mediated diseases, such as tetanus and botulism, little endogenous serum antibody against Stx is induced following EHEC infection (2,21,32). Nonetheless, passively administered toxin-specific antibodies have been shown to be highly effective at preventing toxin-mediated diseases (32).…”

mentioning

confidence: 99%

Human Stx2-Specific Monoclonal Antibodies Prevent Systemic Complications of Escherichia coli O157:H7 Infection

Mukherjee

Chios

Fishwild³

et al. 2002

Infect Immun

102

118

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“…Similar to other toxin-induced diseases, such as tetanus and botulism (85), little endogenous serum antibody is induced against Stx1 or Stx2 following STEC infection (5,112). Nonetheless, passively administered toxin-specific antibodies have been shown to be highly effective at preventing toxin-mediated diseases.…”

Section: Use Of Specific Antibodies In Human Therapymentioning

confidence: 99%

Antibody Therapy in the Management of Shiga Toxin-Induced Hemolytic Uremic Syndrome

et al. 2004

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Hemolytic uremic syndrome (HUS) is a disease that can lead to acute renal failure and often to other serious sequelae, including death. The majority of cases are attributed to infections with Escherichia coli, serotype O157:H7 strains in particular, which cause bloody diarrhea and liberate one or two toxins known as Shiga toxins 1 and 2. These toxins are thought to directly be responsible for the manifestations of HUS. Currently, supportive nonspecific treatment is the only available option for the management of individuals presenting with HUS. The benefit of antimicrobial therapy remains uncertain because of several reports which claim that such intervention can in fact exacerbate the syndrome. There have been only a few specific therapies directed against neutralizing the activities of these toxins, but none so far has been shown to be effective. This article reviews the literature on the mechanism of action of these toxins and the clinical manifestations and current management and treatment of HUS. The major focus of the article, however, is the development and rationale for using neutralizing human antibodies to combat this toxin-induced disease. Several groups are currently pursuing this approach with either humanized, chimeric, or human antitoxin antibodies produced in transgenic mice. They are at different phases of development, ranging from preclinical evaluation to human clinical trials. The information available from preclinical studies indicates that neutralizing specific antibodies directed against the A subunit of the toxin can be highly protective. Such antibodies, even when administered well after exposure to bacterial infection and onset of diarrhea, can prevent the occurrence of systemic complications

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Differences in verotoxin neutralizing activity of therapeutic immunoglobulins and sera from healthy controls

Cited by 32 publications

References 46 publications

Protection of Human Podocytes from Shiga Toxin 2-Induced Phosphorylation of Mitogen-Activated Protein Kinases and Apoptosis by Human Serum Amyloid P Component

Protection of Human Podocytes from Shiga Toxin 2-Induced Phosphorylation of Mitogen-Activated Protein Kinases and Apoptosis by Human Serum Amyloid P Component

Human Stx2-Specific Monoclonal Antibodies Prevent Systemic Complications of Escherichia coli O157:H7 Infection

Antibody Therapy in the Management of Shiga Toxin-Induced Hemolytic Uremic Syndrome

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