title: Does dysregulated complement activation contribute to haemolytic uraemic syndrome secondary to Streptococcus pneumoniae?
abstract: We describe two patients with haemolytic uraemic syndrome (HUS) associated with invasive Streptococcus pneumoniae infection. Both patients had transiently reduced serum concentrations of complement C3. One had reduced expression of CD46 and never recovered renal function. No constitutive defect in regulation of the alternative pathway of complement activation was demonstrated in the second patient but there was an apparent improvement in her condition after administration of eculizumab. The most widely accepted mechanism for pneumococcal HUS is endothelial cell damage by pre-formed antibodies against the Thomsen-Friedenreich antigen. This explanation does not bear rigorous scrutiny. We postulate that transiently dysregulated complement activation may play a role in the pathogenesis of pneumococcal disease. We further postulate that the mechanism could be enhanced binding of factor H to the neuraminidase-altered surface of endothelial cells or reduced binding of factor H to the endothelial cell surface mediated by competitive binding of factor H by pneumococcal surface protein C (pspC).
authors.affiliation: Regional Paediatric Nephro-Urology Unit, University Hospital Southampton, Tremona Road, Southampton SO16 6YD, United Kingdom. Rodney.Gilbert@uhs.nhs.uk
authors.forename: Rodney D
authors.initials: RD
authors.lastname: Gilbert
authors.forename: Arvind
authors.initials: A
authors.lastname: Nagra
authors.forename: Mushfequr R
authors.initials: MR
authors.lastname: Haq
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000494:pharmacology; D003167:Complement Activation / Q000276:immunology*; D003176:Complement C3 / Q000276:immunology*; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology*; D006801:Humans; D007223:Infant; D008297:Male; D051916:Membrane Cofactor Protein / Q000097:blood; D011008:Pneumococcal Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003176:Complement C3; D051916:Membrane Cofactor Protein; C481642:eculizumab