Neural synaptic vesicle autoimmunity following aerosolized porcine neural tissue exposure: insights into autoimmune inflammatory polyradiculoneuropathy
Por:
Hinson, SR, Gupta, P, Paramasivan, NK, Dyck, PJB, Lennon, VA, Lachance, DH, Knight, AM, Rezk, M, Karsten, C, LaFrance-Corey, RG, Staff, NP, Hrstka, SC, Wu, JC, Klein, CJ, Zekeridou, A, Mckeon, A, Pittock, SJ, Lleixà, C, Querol, L, Dasari, S, Mills, JR, Dubey, D
Publicada:
1 dic 2025
Ahead of Print:
1 dic 2025
Resumen:
Background Between 2006 and 2008, cases of occupational inflammatory polyradiculoneuropathy (OIPN) were identified among U.S. swine abattoir workers exposed to aerosolized porcine neural tissue. While the clinical features of this occupational polyradiculoneuropathy/polyradiculopathy have been described, its immunologic basis remained unclear. Methods The archived sera of 20 previously reported OIPN cases were evaluated for putative autoantigens by phage immunoprecipitation sequencing (PhIP-Seq). Healthy and diseased controls and cases of other inflammatory neuropathies, including chronic inflammatory polyradiculoneuropathy (CIDP), Guillain-Barr & eacute; Syndrome (GBS), and axonal/mixed axonal-demyelinating inflammatory polyradiculoneuropathies (IPN, not meeting CIDP/GBS criteria), were also evaluated using by ELISA and CBA. Findings PhIP-Seq data identified synaptophysin and growth-associated protein 43 (GAP43) as dominant autoantigens. Confirmation by enzyme linked immunosorbent assay (ELISA) and cell-based assay (CBA) showed that 11 patients with OIPN sera were positive for both synaptophysin-IgG and GAP43-IgG, four were positive only for synaptophysin-IgG, and one was positive only for GAP43-IgG. Thirteen of 15 (87%) synaptophysin-IgG positive patients had neuropathic pain. Electrodiagnostic features in 12 of 15 (80%) patients with OIPN were of a demyelinating or mixed axonal and demyelinating polyradiculoneuropathy. 12 out of 223 (5%) IPN patients tested positive for synaptophysin-IgG. 67% had demyelinating/mixed axonal-demyelinating electrophysiology, and all except one patient experienced neuropathic pain. Seven synaptophysin-IgG positive cases of spontaneous IPN among nine (78%) who received immunotherapy or cancer-directed therapy showed improvement. Interpretation Our identification of synaptophysin-IgG and GAP43-IgG as biomarkers of an immunotherapyresponsive idiopathic inflammatory polyradiculoneuropathy has diagnostic and therapeutic implications.
Filiaciones:
Hinson, SR:
Mayo Clin, Coll Med, Dept Neurol, 200 1st St SW, Rochester, MN 55906 USA
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
Gupta, P:
Mayo Clin, Coll Med, Dept Neurol, 200 1st St SW, Rochester, MN 55906 USA
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
Paramasivan, NK:
Mayo Clin, Coll Med, Dept Neurol, 200 1st St SW, Rochester, MN 55906 USA
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
Dyck, PJB:
Mayo Clin, Coll Med, Dept Neurol, 200 1st St SW, Rochester, MN 55906 USA
Lennon, VA:
Mayo Clin, Coll Med, Dept Neurol, 200 1st St SW, Rochester, MN 55906 USA
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
Mayo Clin, Coll Med, Dept Immunol, Rochester, MN USA
Lachance, DH:
Mayo Clin, Coll Med, Dept Neurol, 200 1st St SW, Rochester, MN 55906 USA
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
Knight, AM:
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
Rezk, M:
Mayo Clin, Coll Med, Dept Neurol, 200 1st St SW, Rochester, MN 55906 USA
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
Karsten, C:
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
LaFrance-Corey, RG:
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
Staff, NP:
Mayo Clin, Coll Med, Dept Neurol, 200 1st St SW, Rochester, MN 55906 USA
Hrstka, SC:
Mayo Clin, Coll Med, Dept Neurol, 200 1st St SW, Rochester, MN 55906 USA
Wu, JC:
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
Klein, CJ:
Mayo Clin, Coll Med, Dept Neurol, 200 1st St SW, Rochester, MN 55906 USA
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
Zekeridou, A:
Mayo Clin, Coll Med, Dept Neurol, 200 1st St SW, Rochester, MN 55906 USA
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
Mckeon, A:
Mayo Clin, Coll Med, Dept Neurol, 200 1st St SW, Rochester, MN 55906 USA
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
Pittock, SJ:
Mayo Clin, Coll Med, Dept Neurol, 200 1st St SW, Rochester, MN 55906 USA
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
Lleixà, C:
Hosp Santa Creu i St Pau, Neurol Dept, Neuromuscular Dis Unit, IR St PAU, Barcelona, Spain
Querol, L:
Hosp Santa Creu i St Pau, Neurol Dept, Neuromuscular Dis Unit, IR St PAU, Barcelona, Spain
Ctr Invest Red Enfermedades Raras CIBERER, Madrid, Spain
Dasari, S:
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
Mills, JR:
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
Dubey, D:
Mayo Clin, Coll Med, Dept Neurol, 200 1st St SW, Rochester, MN 55906 USA
Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55906 USA
Green Submitted, gold
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