Complement activation in Typical Hemolytic Uremic Syndrome

FERRARIS, J.R.; FERRARIS, V.; SORROCHE, P.; SAEZ, S.; ACQUIER, A.; GINACA, A.; MENDEZ, C.F.

Shanghai

Congreso; The sixteenth Congress of The International Pediatric Nephrology Association; 2013

International Pediatric Nephrology Association

Typical Hemolytic Uremic Syndrome (HUS) is associated with gastrointestinal infection caused by Shiga toxin- (Stx) producing E.Coli. The role of the different complement pathways has not been extensively studied in Stx-associated HUS. Therefore, the aim of this study was to evaluate the activation of the classical and alternative pathways of complement during the acute phase of Stx-HUS. Prospective and longitudinal study including 18 patients diagnosed with Stx-HUS (m/f: 8/10; 32.4 ± 5.4 months-old) as well as 6 age-matched healthy controls. Blood samples were collected daily between admission and discharge from hospital and the levels of C3 and C4 measured by nephelometry and of C3c by immunofixation in serum, whereas the plasma levels of Bb and Sc5b-9 were determined by ELISA. The levels of C3 and C4 at admission were comparable to those of controls (133.6 ± 10.5 vs 127.8 ± 9.0; 26.9 ± 2.9 vs 22.4 ± 1.7 mg/dl, respectively). At admission, levels of Bb, Sc5b-9 and C3c were significantly increased in all patients as compared to controls (6.9 ± 1.3 vs 1.3 ± 0.2; 651.2 ± 130.9 vs 334.8 ± 40.6 ug/ml and 24.9 ± 4.4 vs 12.3 ± 1.4 % of C3, respectively, p<0.05). Elevated concentrations of Bb normalized by day 10, but levels of Sc5b-9 remained elevated until discharge (18 ± 3 days). Levels of Bb were higher in oliguric patients (n=13) vs non-oliguric patients (n=5) (6.8 ± 1.1 vs 3.3 ± 0.4 ug/ml). Positive and significant correlations were detected between C3 and C4, C3c and Bb, C3c and Sc5b-9, Bb and Sc5b-9, blood urea nitrogen and Bb, lactate dehydrogenase and Bb, and negative correlation between thrombocyte count and Bb (p<0.05). Conclusion. Our data demonstrates the activation of the alternative pathway of complement in acute Stx-HUS and points to a pathogenic role of the complement system in the generation of the thrombocytopenia, hemolytic anemia and renal dysfunction observed during the acute phase of the syndrome.