Serological and genetic complement alterations in infection-induced and complement-mediated hemolytic uremic syndrome

Westra, Dineke; Volokhina, Elena; Molen, Renate G. van der; Velden, Thea J A M van der; Jeronimus-Klaasen, Annelies; Goertz, J; Gracchi, Valentina; Dorresteijn, Eiske M.; Bouts, Antonia H.; Keijzer-Veen, Mandy G.; Wijk, J. A. E. van; Bakker, J.; Roos, Anja; Heuvel, Lambert P. van den; Kar, Nicole C. A. J. van de

doi:10.1007/s00467-016-3496-0

Cited by 57 publications

(51 citation statements)

References 50 publications

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“…Furthermore, Stx2 induces the expression of P-selectin on the human microvascular endothelial cell surface, which binds and activates C3 via the alternative pathway, leading to thrombi formation in a murine model of STEC-HUS [189]. Recently, serological and genetic complement alterations were reported in 28% of STEC-HUS children [190]. Nevertheless, these intriguing results have been diminished by the inability to replicate the findings in nonhuman primate models [191].…”

Section: Activation Of Complement Pathways: Culprit or Innocent Bystamentioning

confidence: 99%

Shiga Toxin-Associated Hemolytic Uremic Syndrome: A Narrative Review

Joseph

Cointe

Kurkdjian

et al. 2020

Toxins

155

132

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The severity of human infection by one of the many Shiga toxin-producing Escherichia coli (STEC) is determined by a number of factors: the bacterial genome, the capacity of human societies to prevent foodborne epidemics, the medical condition of infected patients (in particular their hydration status, often compromised by severe diarrhea), and by our capacity to devise new therapeutic approaches, most specifically to combat the bacterial virulence factors, as opposed to our current strategies that essentially aim to palliate organ deficiencies. The last major outbreak in 2011 in Germany, which killed more than 50 people in Europe, was evidence that an effective treatment was still lacking. Herein, we review the current knowledge of STEC virulence, how societies organize the prevention of human disease, and how physicians treat (and, hopefully, will treat) its potentially fatal complications. In particular, we focus on STEC-induced hemolytic and uremic syndrome (HUS), where the intrusion of toxins inside endothelial cells results in massive cell death, activation of the coagulation within capillaries, and eventually organ failure.

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Section: Activation Of Complement Pathways: Culprit or Innocent Bystamentioning

confidence: 99%

Shiga Toxin-Associated Hemolytic Uremic Syndrome: A Narrative Review

Joseph

Cointe

Kurkdjian

et al. 2020

Toxins

155

132

View full text Add to dashboard Cite

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“…Shiga toxin secreted by Escherichia coli or other bacteria is the commonest cause of childhood TMA, typically with a diarrhoeal prodrome and renal failure, and sometimes neurologic impairment . Although bloody diarrhoea is common, this does not reliably distinguish STEC‐HUS from other causes of TMA, notably aHUS . Shiga toxin in contaminated foods traverses the gut lumen, entering the circulation and causing direct endothelial injury, primarily within the glomerular and cerebral microvasculature.…”

Section: Causes Of Tmamentioning

confidence: 99%

“…11 Although bloody diarrhoea is common, this does not reliably distinguish STEC-HUS from other causes of TMA, notably aHUS. 12,13 Shiga toxin in contaminated foods traverses the gut lumen, entering the circulation and causing direct endothelial injury, primarily within the glomerular and cerebral microvasculature. In 1995, contaminated meat products led to an outbreak in South Australia, and in 2011 an epidemic in Germany was traced to contaminated sprouts, resulting in 34 deaths (with adverse outcomes especially common in adults 14 ).…”

Section: Stec-husmentioning

confidence: 99%

Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand

et al. 2018

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Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. While TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4–8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 activity (a disintegrin and metalloprotease thrombospondin, number 13). A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin‐associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC‐HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC‐HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. While early confirmation of aHUS is often not possible, except in the minority of patients in whom autoantibodies against factor H are identified, genetic testing ultimately reveals a complement‐related mutation in a significant proportion of aHUS cases. The presence of other TMA‐associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.

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“…Shiga toxin secreted by E. coli or other bacteria is the commonest cause of childhood TMA, typically with a diarrhoeal prodrome and renal failure, and sometimes neurological impairment . Although bloody diarrhoea is common, this does not reliably distinguish STEC‐HUS from other causes of TMA, notably aHUS . Shiga toxin in contaminated foods traverses the gut lumen, entering the circulation and causing direct endothelial injury, primarily within the glomerular and cerebral microvasculature.…”

Section: Causes Of Tmamentioning

confidence: 99%

Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand

Fox

Cohney

Kausman

et al. 2018

Internal Medicine Journal

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Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. Although TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 (a disintegrin and metalloprotease thrombospondin, number 13) activity. A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. Although early confirmation of aHUS is often not possible, except in the minority of patients in whom auto-antibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.

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Serological and genetic complement alterations in infection-induced and complement-mediated hemolytic uremic syndrome

Cited by 57 publications

References 50 publications

Shiga Toxin-Associated Hemolytic Uremic Syndrome: A Narrative Review

Shiga Toxin-Associated Hemolytic Uremic Syndrome: A Narrative Review

Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand

Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand

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