High serum prevalence of autoreactive IgG antibodies against peripheral nerve structures in patients with neurological post-COVID-19 vaccination syndrome

Front Immunol. 2024 Aug 2:15:1404800. doi: 10.3389/fimmu.2024.1404800. eCollection 2024.

Abstract

Background: Patients suffering from neurological symptoms after COVID-19 vaccination (post-COVID-19 vaccination syndrome (PCVS)) have imposed an increasing challenge on medical practice, as diagnostic precision and therapeutic options are lacking. Underlying autoimmune dysfunctions, including autoantibodies, have been discussed in neurological disorders after SARS-CoV-2 infection and vaccination. Here, we describe the frequency and targets of autoantibodies against peripheral nervous system tissues in PCVS.

Methods: Sera from 50 PCVS patients with peripheral neurological symptoms after COVID-19 vaccination and 35 vaccinated healthy controls were used in this study. IgG autoreactivity was measured via indirect immunofluorescence assays on mouse sciatic nerve teased fibers. The frequencies of autoantibodies were compared between groups using Fisher's exact test. Serum anti-ganglioside antibodies were measured in ganglioside blots. Autoantibody target identification was performed using immunoprecipitation coupled to mass spectrometry. Subsequent target confirmation was conducted via cell-based assays and ELISA.

Results: Compared with controls, PCVS patients had a significantly greater frequency of autoantibodies against peripheral nervous system structures (9/50(18%) vs 1/35(3%); p=0.04). Autoantibodies bound to paranodes (n=5), axons (n=4), Schmidt-Lanterman incisures (n=2) and Schwann cell nuclei (n=1). Conversely, antibodies against gangliosides were absent in PCVS patients. Target identification and subsequent confirmation revealed various subunits of neurofilaments as well as DFS-70 as autoantibody epitopes.

Conclusion: Our data suggest that autoantibodies against nervous system tissue could be relevant in PCVS patients. Autoantibodies against neurofilaments and cell nuclei with so far non-established links to this disease spectrum should be further elucidated to determine their biomarker potential.

Keywords: COVID-19 vaccination; DFS-70; SARS-CoV-2 vaccination; autoantibody; neurofilament autoantibodies; peripheral nerve; post-COVID-19 vaccination syndrome (PCVS).

MeSH terms

  • Adult
  • Aged
  • Animals
  • Autoantibodies* / blood
  • Autoantibodies* / immunology
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • Female
  • Gangliosides / immunology
  • Humans
  • Immunoglobulin G* / blood
  • Immunoglobulin G* / immunology
  • Male
  • Mice
  • Middle Aged
  • Peripheral Nerves / immunology
  • SARS-CoV-2* / immunology
  • Vaccination

Substances

  • Autoantibodies
  • Immunoglobulin G
  • COVID-19 Vaccines
  • Gangliosides

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the German Research Foundation (DFG; Clinical Research Unit KFO 5023 BeCAUSE-Y; project number 504745852; grants FOR3004, PR1274/3–1, PR1274/5–1, and PR1274/9–1; the Helmholtz Association (HIL-A03 BaoBab); and the German Federal Ministry of Education and Research (Connect-Generate 01GM1908D) to HP. ME received funding from DFG under the Germanys Excellence Strategy – EXC-2049 – 390,688,087; Collaborative Research Center ReTune TRR 295–424778381; Clinical Research Group KFO 5023 BeCAUSE-Y; project 2 EN343/16–1; BMBF; DZNE; DZHK; the EU; the Corona Foundation; and Fondation Leducq.