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Updated: Mar 17, 2026
Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
Published on: January 29, 2014
Typical Hus: Evidence of Acute Phase Complement Activation from a Daycare Outbreak
Tammy M Brady1, Cozumel Pruette1, Lauren F Loeffler1
1Division of Pediatric Nephrology, Johns Hopkins University School of Medicine, USA.
Insights
Shiga toxin-positive E. coli (STEC)-hemolytic uremic syndrome (HUS) involves complement activation. Early complement blockade with eculizumab may be a promising treatment for STEC-HUS, warranting further investigation.
Area of Science:
- Nephrology
- Pediatrics
- Immunology
Background:
- Hemolytic uremic syndrome (HUS) has severe potential sequelae, yet treatment remains supportive.
- Shiga toxin-positive E. coli (STEC) infections can cause HUS, particularly during outbreaks.
- The role of complement activation in STEC-HUS requires further elucidation.
Purpose of the Study:
- To investigate the role of complement activation in a pediatric case of STEC-HUS.
- To explore the potential therapeutic effect of complement inhibition in STEC-HUS.
Main Methods:
- A modified Ham test was used to assess complement activation in patient serum.
- In vitro experiments utilized Shiga toxin to stimulate complement activation in normal serum.
- The effect of eculizumab on complement activation was evaluated in vitro.
Main Results:
- Patient sera showed increased complement activation during the acute phase of STEC-HUS, which resolved post-illness.
- Shiga toxin stimulated complement activation in normal serum in vitro.
- Eculizumab attenuated complement activation in patient serum and in vitro stimulated serum.
Conclusions:
- Complement activation is implicated in the pathogenesis of STEC-HUS.
- Early complement blockade, potentially with eculizumab, may be an effective treatment strategy for STEC-HUS.
- Further research, including clinical trials, is needed to confirm the efficacy of early eculizumab treatment for STEC-HUS.
Abstract:
The clinical manifestations of typical hemolytic uremic syndrome (HUS) encompass a wide spectrum. Despite the potentially severe sequelae from this syndrome, treatment approaches remain supportive. We present the clinical course of a child who contracted Shiga toxin-positive E. coli (STEC) from a daycare center during an outbreak. Utilizing the modified Ham test which is a rapid, serum-based functional assay used to detect activation of the alternative pathway of complement as observed in atypical HUS, patient sera revealed evidence of increased complement activation in the acute phase of the syndrome but not after resolution. Further, this complement activation was attenuated by eculizumab in vitro, an effect that was replicated in vitro utilizing Shiga toxin as a stimulus of complement activation in normal serum. Our report suggests that complement blockade may be effective in the treatment of STEC-HUS when initiated early in the disease. Given the epidemic nature of the disease that limits the feasibility of randomized clinical trials, further studies are needed to determine the value of early eculizumab treatment in STEC-HUS.
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