ESPN 53rd Annual Meeting

ESPN 2021

Marloes A.H.M. Michels 1 Elena B. Volokhina 1 Janne de Klein 1 Roel A.J. Kurvers 1 Kioa L. Wijnsma 1 Joanna A.E. van Wijk 2 Antonia H. Bouts 2 Valentina Gracchi 3 Flore Horuz 4 Mandy G. Keijzer-Veen 5 Eiske M. Dorresteijn 6 Lambertus P.W.J. van den Heuvel 1 Nicole C.A.J. van de Kar 1

1- Department of Pediatric Nephrology, Amalia Children’s Hospital, Radboud university medical center, Nijmegen, The Netherlands
2- Department of Pediatric Nephrology, Emma Children’s Hospital, Amsterdam University Medical Center, Amsterdam, The Netherlands
3- Department of Pediatric Nephrology, Beatrix Children’s Hospital, University of Groningen, Groningen, The Netherlands
4- Department of Pediatric Nephrology, Academic Medical Center Maastricht, Maastricht, The Netherlands
5- Department of Pediatric Nephrology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
6- Department of Pediatric Nephrology, Sophia Children’s Hospital, Erasmus Medical Center, Rotterdam, The Netherlands

C3 glomerulopathy (C3G) is a rare kidney disorder characterized by predominant glomerular depositions of complement C3, resulting from alternative pathway (AP) dysregulation. C3G can be subdivided into dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). In this study we retrospectively analyzed the presence of complement-directed autoantibodies and the complement biomarker profiles of 29 pediatric C3G patients.


Material and methods:

C3 levels were retrieved from the patient files. The complement activation markers C3bBbP (properdin-stabilized C3 convertase), C3bc (C3 activation products), soluble C5b-9 (sC5b-9; terminal complement complex), complement component C5, positive regulator properdin, and negative complement regulators Factor H (FH) and Factor I were measured using sandwich ELISA. Convertase activity assays were used to detect the presence of C3 nephritic factors (C3NeFs) and C4 nephritic factors (C4NeFs). ELISA was used to screen for FH autoantibodies.



C3NeFs were found in 20/28 patients (12/18 DDD, 8/10 C3GN). One patient (DDD) additionally carried C4NeFs and two patients (1 DDD, 1 C3GN) additionally carried FH autoantibodies. C3NeFs remained detectable over time despite immunosuppressive treatment. At presentation, C3 levels were decreased in 21/25 patients, indicating complement consumption. During follow-up, in about 50% of patients, all of them C3NeF-positive, C3 levels remained low. Linear mixed model analysis showed that C3GN patients had higher sC5b-9 and lower properdin levels compared to DDD patients.



The majority of pediatric patients with C3G show signs of complement activation in their blood. C3NeFs were associated with lower C3 levels at last measurement. C3GN patients showed higher sC5b-9 and lower properdin levels compared to DDD patients. These findings may aid in further understanding the AP dysregulation in C3G and in the development and monitoring of novel complement-directed treatment strategies in the near future. Given the rarity and heterogeneity of C3G, prospective longitudinal studies are needed to further investigate the complement profiles over time in C3G.