Increased levels of antibodies to synaptopodin and annexin 1 in patients with primary podocytopathies

Natalia V Chebotareva; Evgeniya A Charionovskaya; Evgenia A Biryukova; Anatoliy A Vinogradov; Igor I Alentov; Natalia S Sergeeva; Alexey S Kononikhin; Evgeny N Nikolaev; Sergey V Moiseev

doi:10.3389/fneph.2024.1471078

Increased levels of antibodies to synaptopodin and annexin 1 in patients with primary podocytopathies

Front Nephrol. 2024 Oct 31:4:1471078. doi: 10.3389/fneph.2024.1471078. eCollection 2024.

Authors

Natalia V Chebotareva¹, Evgeniya A Charionovskaya¹, Evgenia A Biryukova¹, Anatoliy A Vinogradov², Igor I Alentov³, Natalia S Sergeeva³, Alexey S Kononikhin⁴, Evgeny N Nikolaev⁴, Sergey V Moiseev¹

Affiliations

¹ Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russia.
² Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russia.
³ Department of Prediction of Conservative Treatment Efficiency, Hertsen Moscow Oncology Research Institute, Moscow, Russia.
⁴ Project Center of Advanced Mass, Spectrometry Technologies, Skolkovo Institute of Science and Technology, Moscow, Russia.

Abstract

Introduction: Circulating anti-podocyte antibodies have been proposed as potential factors contributing to increased permeability in primary podocytopathies, such as Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS). The aim of the study was to to assess the levels of antibodies targeting synaptopodin and annexin 1 in the blood serum of patients diagnosed with nephrotic syndrome, with the aim of evaluating their potential utility in diagnosing primary podocytopathies and predicting therapeutic response.

Methods: The study included a total of 72 patients diagnosed with nephrotic syndrome, alongside 21 healthy subjects for comparison. Among the patients, 38 were diagnosed with FSGS, 12 with MCD, and 22 with MN. The levels of anti-synaptopodin and anti-annexin-1 antibodies were quantified using Enzyme-Linked Immunosorbent Assay.

Results: The levels of antibodies to annexin 1 and anti-synaptopodin in the blood were found to be higher in patients diagnosed with MCD and FSGS compared to those with MN and healthy individuals. The elevated levels of antibodies to annexin 1 and synaptopodin showed area under the curve values of 0.826 (95% CI 0.732-0.923) and 0.827 (95% CI 0.741-0.879), respectively. However, a model incorporating both antibodies demonstrated higher sensitivity (80.9%) and specificity (81.3%) with an AUC of 0.859 (95% CI 0.760-0.957). Notably, serum levels of annexin 1 and anti-synaptopodin antibodies did not predict the response to prednisolone and/or CNI therapy.

Discussion: Levels of antibodies targeting synaptopodin and annexin 1 were notably elevated in patients diagnosed with MCD and FSGS compared to those with MN and healthy controls. A panel comprising both antibodies demonstrated moderate to high sensitivity and specificity for diagnosis MCD or FSGS.

Keywords: annexin 1; focal segmental glomerulosclerosis; minimal change disease; podocytopathy; synaptopodin.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the Russian Science Foundation, grant #21-74-20173.