Background. Atypical forms of haemolytic uraemic syndrome
(aHUS) include HUS caused by defects in the regulation of
alternative complement pathway and HUS linked to neuraminidase-
producing pathogens, such as Streptococcus pneumoniae.
Increasing data support a pathogenic role of neuraminidase in
the development of S. pneumoniae-associated haemolytic
uraemic syndrome (SP-HUS), but the role of complement has
never been clarified in detail. Therefore, we aimed to investigate
whether the pathologic complement profile and genetic risk
factors of aHUS are present in patients with SP-HUS.
Methods. Enrolling five patients with SP-HUS classical and
alternative pathway activity, besides C3, C4, factors H, B, I and
anti-factor H autoantibody levels were determined. The
coding regions of CFH, CFI, CD46 (MCP), THBD, C3 and
CFB genes were sequenced and the copy number of CFI,
CD46, CFH and related genes were also analyzed.
Results. We found that in the acute phase samples of SP-HUS
patients, complement components C4, C3 and activity of the
classical and alternative pathways were decreased, indicating
severe activation and complement consumption, but most of
these alterations normalized later in remission. Three of the
patients carried mutations and risk haplotypes in complement-
mediated aHUS associated genes. The identifiedmutations include a previously published CFI variant (P50A)
and two novel ones in CFH (R1149X) and THBD (T44I)
genes.
Conclusions. Our results suggest that severe complement dysregulation
and consumption accompany the progress of invasive
pneumococcal disease (IPD)-associated SP-HUS and
genetic variations of complement genes may contribute to the
development of this complication in a proportion of the affected
patients
