Hemolytic Uremic Syndrome Attributable to Streptococcus pneumoniae Infection: A Novel Cause for Secondary Protein N-Glycan Abnormalities

Loos, Femke de; Huijben, Karin; Kar, Nicole C.A.J. van der; Monnens, L.A.H.; Heuvel, L.P.W.J. van den; Groener, J.E.M.; Moor, Ronald A. de; Wevers, Ron A.

doi:10.1093/clinchem/48.5.781

Cited by 20 publications

(10 citation statements)

References 13 publications

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“…De Loos et al reported the desialylation of transferrin N-glycan and suggested that the abnormal transferrin N-glycosylation pattern was helpful in distinguishing P-HUS from other HUS forms. 2 S. pneumoniae expresses up to three sialidases, NanA, NanB and NanC, among which NanA and NanB are validated peumococcal virulence factors and potential drug targets. NanA is invariably present in the S. pneumoniae strains isolated from clinical samples and has no preference for α2,3or α2,6-linkages, and the exposure of T-antigen in vivo is dependent on NanA.…”

Section: Discussionmentioning

confidence: 99%

“…Desialylation of the cell surface O-glycans and serum transferrin N-glycans has been reported in HUS. 2 Herein, we describe a pneumococcal HUS (P-HUS) case in which decreased sialylation of IgA1 was characterized on a molecular basis on mass spectrometry (MS). To the best of our knowledge, this is the first report of desialylation of plasma O-glycosylated proteins associated with P-HUS.…”

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confidence: 99%

“…This mechanism may be implicated in the development of manifestations such as anemia, thrombocytopenia and uremia. Desialylation of the cell surface O ‐glycans and serum transferrin N ‐glycans has been reported in HUS . Herein, we describe a pneumococcal HUS (P‐HUS) case in which decreased sialylation of IgA1 was characterized on a molecular basis on mass spectrometry (MS).…”

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confidence: 99%

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Decreased sialylation of IgA1 O‐glycans associated with pneumococcal hemolytic uremic syndrome

Aoki

Shiomi

Ikeda

et al. 2013

Pediatrics International

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Hemolytic uremic syndrome (HUS) in children is usually caused by Shiga-like toxin-producing Escherichia coli, but approximately 5% of cases are caused by invasive pneumococcal infection (P-HUS). Reported herein is the case of a 9-month-old HUS patient with pneumococcal meningitis who needed hemodialysis for 12 days. Decreased sialylation was characterized in both transferrin N-glycans and IgA1 O-glycans, analyzed in the acute phase on mass spectrometry, consistent with S. pneumonia-produced sialidases hydrolyzing both α2,3- and α2,6-linked sialic acids. The method will complement the T-antigen activation test and help to understand the molecular pathology related to P-HUS.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Decreased sialylation of IgA1 O‐glycans associated with pneumococcal hemolytic uremic syndrome

Aoki

Shiomi

Ikeda

et al. 2013

Pediatrics International

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“…The occurrence, however, is rare as only samples of two patients with such a transferrin pattern were analyzed in a 10-year period during which a total of about 4500 samples from the hepatology outpatient clinic were analyzed. Such hyposialylated Tf glycoforms are also characteristic for sera with neuraminidase activity, including those of patients with hemolytic uremic syndrome associated with a Streptococcus pneumoniae infection [47,48].…”

Section: Transferrin Patterns Of Mixed Type I/ii Patientsmentioning

confidence: 99%

High‐resolution capillary zone electrophoresis for transferrin glycoform analysis associated with congenital disorders of glycosylation

Tobler

Caslavska

Burda

et al. 2018

J of Separation Science

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High-resolution capillary zone electrophoresis is used to assess the transferrin profile in serum of patients with eight different congenital disorders of glycosylation that represent type I, type II, and mixed type I/II disorders. Capillary zone electrophoresis data are compared to patterns obtained by gel isoelectric focusing. The high-resolution capillary zone electrophoresis method is shown to represent an effective tool to assess the diversity of transferrin patterns. Hypoglycosylated disialo-, monosialo-, and asialo-transferrin in type I cases can be distinguished from the corresponding underdesialylated transferrin glycoforms present in type II disorders. The latter can be separated from and detected ahead of their corresponding hypoglycosylated forms of type I patients. Both types of glycoforms are detected in sera of mixed type I/II patients. The assay has the potential to be used as screening method for congenital disorders of glycosylation. It can be run with a few microliters of serum when microvials are used.

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“…Auch methodenbedingt können falsch positive Werte bestimmt werden, wenn beispielsweise EDTA-Plasma anstelle von Serum verwendet wird [10]. Auch soll eine zu lange Zeitspanne zwischen Gewinnung und Zentrifugation der Probe ein falsch positives CDT-Testergebnis bedingen [31] [23,24] -Hämolytisch urämisches Syndrom (HUS) [25] -Eisenmangelanämie, Ferritinmangel [26,27] -Eisenreduktionsbehandlung bei Hämochromatose [26,28] -Prämenopause [29] -Achondroplasie [30] Methodisch bedingt -Transferrin-(Tf-)D-Varianten [4, 9 -12] -Zu lange Probenlagerung [31] -Insuffiziente Eisensättigung von Tf bei Verwendung von EDTA-Plasma statt Serum [10] CDT falsch erniedrigt -Transferrin-(Tf)-B-Varianten [9] -Hereditäre Hämochromatose [26] -Erhöhte Eisenspeicher [26]…”

Section: Introductionunclassified

Identifizierung eines mittels Immunturbidimetrie nach Anionenaustausch-Chromatographie erhöhten Carbohydrate-Deficient-Transferrin-(CDT-)Serumspiegels als Transferrin (Tf)-D-Variante

et al. 2004

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Many studies have shown carbohydrate-deficient transferrin (CDT) to be a sensitive and specific marker of chronic alcohol abuse. We present the case of a 23-year-old, healthy professional soccer player who caused a car accident due to alcohol consumption. Several CDT test results were elevated above the laboratory reference range and were considered to be caused by alcohol intake at a level commensurate with misuse and thus license reapplication was refused. In addition, assuming chronic alcohol abuse, the young man suffered from increasing social isolation. He was finally referred to our out-patient clinic for further evaluation on the assumption of a liver disease. Since chronic alcohol consumption was denied, and there was no evidence of liver disease, a qualitative characterization of the transferrin isoforms was performed. Isoelectric focusing of serum transferrin revealed a pattern atypical for chronic alcohol intake but detected a genetically determined transferrin (Tf)-D-variant. The changed amino acid sequence caused an overlapping of transferrin isoforms with different degrees of sialylation, thus revealing false-positive serum CDT values. Determination of this Tf-D-variant heterozygosity resulted in his social rehabilitation and license reinstatement. Thus, where the evidence for alcohol dependency is either uncertain or uncorroborated, qualitative isoelectric focusing of transferrin is a useful method for analyzing unexplained CDT elevations, thus increasing the value of CDT as a marker for chronic alcoholic abuse.

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Hemolytic Uremic Syndrome Attributable to Streptococcus pneumoniae Infection: A Novel Cause for Secondary Protein N-Glycan Abnormalities

Cited by 20 publications

References 13 publications

Decreased sialylation of IgA1 O‐glycans associated with pneumococcal hemolytic uremic syndrome

Decreased sialylation of IgA1 O‐glycans associated with pneumococcal hemolytic uremic syndrome

High‐resolution capillary zone electrophoresis for transferrin glycoform analysis associated with congenital disorders of glycosylation

Identifizierung eines mittels Immunturbidimetrie nach Anionenaustausch-Chromatographie erhöhten Carbohydrate-Deficient-Transferrin-(CDT-)Serumspiegels als Transferrin (Tf)-D-Variante

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