Anti-nephrin autoantibodies in steroid-resistant nephrotic syndrome may inform treatment strategy
Felicitas E. Hengel, Silke Dehde, Alev Yılmaz, Aysun Karabay Bayazıt, Fatih Özaltın, Dušan Paripović, Francesco Emma, Pierre Ronco, Marina Vivarelli, Julien Hogan, Franz Schaefer, Nicola M. Tomas, Tobias B. Huber
Abstract
INTRODUCTION: Autoantibodies against the podocyte protein nephrin were recently identified in a pediatric cohort primarily comprising steroid-sensitive (SSNS) and steroid-dependent (SDNS) nephrotic syndrome (NS). However, their prevalence across all NS subtypes, particularly in steroid-resistant nephrotic syndrome (SRNS), and their relation to therapy response need to be determined to advance pathophysiological understanding and refine treatment strategies. METHODS: A multicenter cohort study measuring anti-nephrin autoantibodies in samples from children with SSNS, SDNS, nongenetic and genetic SRNS was conducted. RESULTS: Sixty-nine of 101 (68%) patients with SSNS, 19 of 67 (28%) patients with SDNS, 14 of 103 patients (14%) with non-genetic SRNS, and 1 of 62 patients (2%) with genetic SRNS were positive for anti-nephrin autoantibodies. The prevalence of anti-nephrin autoantibodies increased with presence of active disease in cases of SSNS and SDNS. Within the group of non-genetic SRNS patients with active disease, anti-nephrin positivity was found in 13 of 74 (18%) patients responding to intensified immunosuppression compared to none of 17 patients with multidrug-resistant SRNS. CONCLUSIONS: The prevalence of anti-nephrin antibodies is substantially higher in children with steroid responsive NS than in those with SRNS, suggesting that anti-nephrin antibodies primarily drive SSNS/SDNS. In contrast, NS due to podocyte gene mutations is primarily genotype-caused. Anti-nephrin autoantibodies may serve as a positive prognostic marker in pediatric NS, indicating a favorable response to immunosuppressive therapy.