Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Rare genetic variants in Shiga toxin-associated haemolytic uraemic syndrome: genetic analysis prior to transplantation is essential.

ABSTRACT: We present a case of haemolytic uraemic syndrome (HUS) in a 16-year-old female with serological evidence of acute Escherichia coli O157:H7 infection. She progressed to established renal failure and received a deceased donor kidney transplant. Shiga toxin-associated HUS (STEC-HUS) does not recur following renal transplantation, but unexpectedly this patient did experience rapid and severe HUS recurrence. She responded to treatment with the terminal complement inhibitor eculizumab and subsequent genetic analysis revealed a rare variant in a complement gene. This highlights the importance of genetic analysis in patients with STEC-HUS prior to renal transplantation so that management can be individualized.

SUBMITTER: Dowen F

PROVIDER: S-EPMC5569917 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Rare genetic variants in Shiga toxin-associated haemolytic uraemic syndrome: genetic analysis prior to transplantation is essential.

Dowen Frances F Wood Katrina K Brown Alison L AL Palfrey Jennifer J Kavanagh David D Brocklebank Vicky V

Clinical kidney journal 20170508 4

We present a case of haemolytic uraemic syndrome (HUS) in a 16-year-old female with serological evidence of acute Escherichia coli O157:H7 infection. She progressed to established renal failure and received a deceased donor kidney transplant. Shiga toxin-associated HUS (STEC-HUS) does not recur following renal transplantation, but unexpectedly this patient did experience rapid and severe HUS recurrence. She responded to treatment with the terminal complement inhibitor eculizumab and subse ...[more]

PMID: 28852487

Similar Datasets

Eculizumab in the treatment of Shiga toxin haemolytic uraemic syndrome.

Project description:Haemolytic uraemic syndrome (HUS) remains a leading cause of paediatric acute kidney injury (AKI). Haemolytic uraemic syndrome is characterised by the triad of microangiopathic haemolytic anaemia, thrombocytopenia and AKI. In ~ 90% of cases, HUS is a consequence of infection with Shiga toxin-producing E. coli (STEC), most commonly serotype O157:H7. Acute mortality from STEC-HUS is now less than 5%; however, there is significant long-term renal morbidity in one third of survivors. Currently, no specific treatment exists for STEC-HUS. There is growing interest in the role of complement in the pathogenesis of STEC-HUS due to the discovery of inherited and acquired dysregulation of the alternative complement system in the closely related disorder, atypical HUS (aHUS). The treatment of aHUS has been revolutionised by the introduction of the anti-C5 monoclonal antibody, eculizumab. However, the role of complement and anti-complement therapy in STEC-HUS remains unclear. Herein, we review the current evidence of the role of complement in STEC-HUS focusing on the use of eculizumab in this disease.

| S-EPMC6660499 | biostudies-literature

Shiga toxin-producing Escherichia coli O26:H11 associated with a cluster of haemolytic uraemic syndrome cases in South Africa, 2017.

Project description:Introduction:Shiga toxin-producing Escherichia coli (STEC) are foodborne pathogens that may cause diarrhoeal outbreaks and occasionally are associated with haemolytic-uraemic syndrome (HUS). We report on STEC O26:H11 associated with a cluster of four HUS cases in South Africa in 2017. Methodology:All case-patients were female and aged 5 years and under. Standard microbiological tests were performed for culture and identification of STEC from specimens (human stool and food samples). Further analysis of genomic DNA extracted from bacterial cultures and specimens included PCR for specific virulence genes, whole-genome sequencing and shotgun metagenomic sequencing. Results:For 2/4 cases, stool specimens revealed STEC O26:H11 containing eae, stx2a and stx2b virulence genes. All food samples were found to be negative for STEC. No epidemiological links could be established between the HUS cases. Dried meat products were the leading food item suspected to be the vehicle of transmission for these cases, as 3/4 case-patients reported they had eaten this. However, testing of dried meat products could not confirm this. Conclusion:Since STEC infection does not always lead to severe symptoms, it is possible that many more cases were associated with this cluster and largely went unrecognized.

| S-EPMC7472548 | biostudies-literature

Virulence factors of Shiga toxin-producing Escherichia coli and the risk of developing haemolytic uraemic syndrome in Norway, 1992-2013.

Project description:Shiga toxin-producing Escherichia coli (STEC) may cause haemolytic uraemic syndrome (HUS). Age ≤5 years and presence of stx2a and eae are risk factors for the development of HUS. In this study, we investigated STEC isolates for the presence of adhesins, toxins and molecular risk assessment (MRA) factors to identify virulence genes associated with HUS development. We included non-duplicate isolates from all STEC infections (n = 340, HUS = 32) reported to the Norwegian National Reference Laboratory (NRL) for Enteropathogenic Bacteria from 1992 to 2013. The most common STEC were O157:H7/H- (34%) and O103:H2 (14%). We retrospectively screened the isolates by three multiplex polymerase chain reactions (PCRs) for adhesins (n = 11), toxins (n = 5) and MRA (n = 15). We calculated odds ratios (ORs) and adjusted odds ratios (aORs) for associations with HUS development. On average, isolates were positive for 15 virulence genes (range: 1-24); two toxins (range: 0-4), five adhesins (range: 0-8) and eight MRA genes (range: 0-13). The gene combinations were clustered within serotypes. Isolates from HUS cases were positive for eae and IpfA O26, and negative for saa, eibG, astA, cnf, subA and pic. We identified 11 virulence genes with a significant association to HUS development. Multivariable analyses adjusted for age group and Shiga toxin identified nleH1-2 [aOR 8.4, 95% confidence interval (CI); 2.18-32.3] as an independent risk factor for the development of HUS from an STEC infection. This study demonstrated that the non-LEE effector protein nleH1-2 may be an important predictor for elevated risk of developing HUS from STEC infections. We recommend the NRL for Enteropathogenic Bacteria to consider including nleH1-2 screening as part of routine STEC surveillance.

| S-EPMC5554284 | biostudies-literature

Complement Genetic Variants and FH Desialylation in S. pneumoniae-Haemolytic Uraemic Syndrome.

Project description:Haemolytic Uraemic Syndrome associated with Streptococcus pneumoniae infections (SP-HUS) is a clinically well-known entity that generally affects infants, and could have a worse prognosis than HUS associated to E. coli infections. It has been assumed that complement genetic variants associated with primary atypical HUS cases (aHUS) do not contribute to SP-HUS, which is solely attributed to the action of the pneumococcal neuraminidase on the host cellular surfaces. We previously identified complement pathogenic variants and risk polymorphisms in a few Hungarian SP-HUS patients, and have now extended these studies to a cohort of 13 Spanish SP-HUS patients. Five patients presented rare complement variants of unknown significance, but the frequency of the risk haplotypes in the CFH-CFHR3-CFHR1 region was similar to the observed in aHUS. Moreover, we observed desialylation of Factor H (FH) and the FH-Related proteins in plasma samples from 2 Spanish and 4 Hungarian SP-HUS patients. To analyze the functional relevance of this finding, we compared the ability of native and "in vitro" desialylated FH in: (a) binding to C3b-coated microtiter plates; (b) proteolysis of fluid-phase and surface-bound C3b by Factor I; (c) dissociation of surface bound-C3bBb convertase; (d) haemolytic assays on sheep erythrocytes. We found that desialylated FH had reduced capacity to control complement activation on sheep erythrocytes, suggesting a role for FH sialic acids on binding to cellular surfaces. We conclude that aHUS-risk variants in the CFH-CFHR3-CFHR1 region could also contribute to disease-predisposition to SP-HUS, and that transient desialylation of complement FH by the pneumococcal neuraminidase may have a role in disease pathogenesis.

| S-EPMC7991904 | biostudies-literature

Ongoing haemolytic uraemic syndrome (HUS) outbreak caused by sorbitol-fermenting (SF) Shiga toxin-producing Escherichia coli (STEC) O157, Germany, December 2016 to May 2017.

Project description:We report an ongoing, protracted and geographically dispersed outbreak of haemolytic uraemic syndrome (HUS) and gastroenteritis in Germany, involving 30 cases since December 2016. The outbreak was caused by the sorbitol-fermenting immotile variant of Shiga toxin-producing (STEC) Escherichia coli O157. Molecular typing revealed close relatedness between isolates from 14 cases. One HUS patient died. Results of a case-control study suggest packaged minced meat as the most likely food vehicle. Food safety investigations are ongoing.

| S-EPMC5479985 | biostudies-literature

Estimating true incidence of O157 and non-O157 Shiga toxin-producing Escherichia coli illness in Germany based on notification data of haemolytic uraemic syndrome.

Project description:Shiga toxin-producing Escherichia coli (STEC) is an important cause of gastroenteritis (GE) and haemolytic uraemic syndrome (HUS). Incidence of STEC illness is largely underestimated in notification data, particularly of serogroups other than O157 ('non-O157'). Using HUS national notification data (2008-2012, excluding 2011), we modelled true annual incidence of STEC illness in Germany separately for O157 and non-O157 STEC, taking into account the groups' different probabilities of causing bloody diarrhoea and HUS, and the resulting difference in their under-ascertainment. Uncertainty of input parameters was evaluated by stochastic Monte Carlo simulations. Median annual incidence (per 100 000 population) of STEC-associated HUS and STEC-GE was estimated at 0·11 [95% credible interval (CrI) 0·08-0·20], and 35 (95% CrI 12-145), respectively. German notification data underestimated STEC-associated HUS and STEC-GE incidences by factors of 1·8 and 32·3, respectively. Non-O157 STEC accounted for 81% of all STEC-GE, 51% of all bloody STEC-GE and 32% of all STEC-associated HUS cases. Non-O157 serogroups dominate incidence of STEC-GE and contribute significantly to STEC-associated HUS in Germany. This might apply to many other countries considering European surveillance data on HUS. Non-O157 STEC should be considered in parallel with STEC O157 when searching aetiology in patients with GE or HUS, and accounted for in modern surveillance systems.

| S-EPMC9150202 | biostudies-literature

Epidemiological investigation of recurrent outbreaks of haemolytic uraemic syndrome caused by Shiga toxin-producing Escherichia coli serotype O55:H7 in England, 2014-2018.

Project description:Recurrent outbreaks of haemolytic uraemic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) serotype O55:H7 occurred in England between 2014 and 2018. We reviewed the epidemiological evidence to identify potential source(s) and transmission routes of the pathogen, and to assess the on-going risk to public health. Over the 5-year period, there were 43 confirmed and three probable cases of STEC O55:H7. The median age of cases was 4 years old (range 6 months to 69 years old) and over half of all cases were female (28/46, 61%). There were 36/46 (78.3%) symptomatic cases, and over half of all cases developed HUS (25/46, 54%), including two fatal cases. No common food or environmental exposures were identified, although the majority of cases lived in rural or semi-rural environments and reported contact with both wild and domestic animals. This investigation informed policy on the clinical and public health management of HUS caused by STEC other than serotype O157:H7 (non-O157 STEC) in England, including comprehensive testing of all household contacts and household pets and more widespread use of polymerase chain reaction assays for the rapid diagnosis of STEC-HUS.

| S-EPMC8161408 | biostudies-literature

Atypical haemolytic uraemic syndrome: a case report of a rare cause of reversible cardiomyopathy.

Project description:Background:Atypical haemolytic uraemic syndrome (aHUS) is a life-threatening, genetic disease of complement-mediated thrombotic microangiopathy that typically presents as anaemia, thrombocytopenia, and renal failure. Cardiomyopathy is seen in up to 10% of aHUS cases, but the aetiology is not well-understood. Case summary:A 63-year-old man recently was diagnosed with a thrombotic microangiopathy most consistent with aHUS by renal biopsy after presentation with acute renal failure requiring haemodialysis. He was started on therapy with complement inhibitor, eculizumab. Six weeks after diagnosis, he presented with progressive dyspnoea on exertion and chest pain. An echocardiogram demonstrated an acute drop in left ventricular ejection fraction to 20-25% with global hypokinesis. Left heart catheterization showed moderate, non-obstructive coronary artery disease. Cardiac magnetic resonance imaging demonstrated diffuse myocardial oedema. Endomyocardial biopsy revealed an arteriole with obliterative changes and a few possible fragmented red blood cells suggestive of thrombotic microangiopathy. There was no biopsy evidence of immune complex deposition or myocarditis. He was treated for heart failure and was maintained on eculizumab. On repeat echocardiogram 3 months later, the patient had complete recovery of his ejection fraction (60-65%). Discussion:In this report, we describe complete recovery of aHUS-associated heart failure with eculizumab therapy and demonstrate for the first time that the aetiology of aHUS-associated heart failure is likely an acute thrombotic microangiopathy involving small intramyocardial arterioles, as demonstrated by cardiac biopsy.

| S-EPMC7180527 | biostudies-literature

Eculizumab in secondary atypical haemolytic uraemic syndrome.

Project description:BackgroundComplement dysregulation occurs in thrombotic microangiopathies (TMAs) other than primary atypical haemolytic uraemic syndrome (aHUS). A few of these patients have been reported previously to be successfully treated with eculizumab.MethodsWe identified 29 patients with so-called secondary aHUS who had received eculizumab at 11 Spanish nephrology centres. Primary outcome was TMA resolution, defined by a normalization of platelet count (>150 × 10 9 /L) and haemoglobin, disappearance of all the markers of microangiopathic haemolytic anaemia (MAHA), and improvement of renal function, with a ≥25% reduction of serum creatinine from the onset of eculizumab administration.ResultsTwenty-nine patients with secondary aHUS (15 drug-induced, 8 associated with systemic diseases, 2 with postpartum, 2 with cancer-related, 1 associated with acute humoral rejection and 1 with intestinal lymphangiectasia) were included in this study. The reason to initiate eculizumab treatment was worsening of renal function and persistence of TMA despite treatment of the TMA cause and plasmapheresis. All patients showed severe MAHA and renal function impairment (14 requiring dialysis) prior to eculizumab treatment and 11 presented severe extrarenal manifestations. A rapid resolution of the TMA was observed in 20 patients (68%), 15 of them showing a ≥50% serum creatinine reduction at the last follow-up. Comprehensive genetic and molecular studies in 22 patients identified complement pathogenic variants in only 2 patients. With these two exceptions, eculizumab was discontinued, after a median of 8 weeks of treatment, without the occurrence of aHUS relapses.ConclusionShort treatment with eculizumab can result in a rapid improvement of patients with secondary aHUS in whom TMA has persisted and renal function worsened despite treatment of the TMA-inducing condition.

| S-EPMC5410989 | biostudies-literature

Ravulizumab: A Review in Atypical Haemolytic Uraemic Syndrome.

Project description:Ravulizumab (Ultomiris®), a humanized monoclonal antibody that inhibits complement protein C5, is indicated for the treatment of atypical haemolytic uraemic syndrome (aHUS) in several countries, including the USA and those of the EU. Ravulizumab has been re-engineered from eculizumab to extend its terminal elimination half-life, resulting in a more convenient maintenance dosage regimen of once every 4-8 weeks compared with once every 2-3 weeks for eculizumab. In single-arm phase 3 trials, ravulizumab resolved thrombotic microangiopathy in 54% and 78% of treatment-naïve adult and paediatric patients with aHUS, respectively, within 26 weeks. Ravulizumab was also effective in patients with postpartum aHUS and paediatric patients who responded to eculizumab and later switched to ravulizumab. Ravulizumab was generally well tolerated, with no unexpected safety events. The most common treatment-related adverse events with ravulizumab in treatment-naïve patients include headache, diarrhoea and vomiting. With its convenient once every 4-8 weeks maintenance regimen, ravulizumab is an important treatment option for aHUS in adult and paediatric patients.

| S-EPMC8052220 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data