This study examined whether neutrophil extracellular traps (NETs) drive neuropathic pain in primary Sjögren's syndrome-associated peripheral neuropathy (pSS-PN), using sural nerve biopsies from 6 pSS-PN patients and 6 controls, plus a NOD.Aire⁻/⁻ mouse model treated with DNase I to inhibit NETosis.
pSS-PN patients showed cit-H3/MPO accumulation in vasa nervorum. NOD.Aire⁻/⁻ mice developed mechanical allodynia and thermal hyperalgesia vs. controls (P < 0.05–0.001), with elevated plasma cit-H3 (44.61 vs. 27.49 ng/mL, P < 0.0001 vs. C57BL/6J). DNase I treatment reduced plasma cit-H3, relieved pain behaviors, and normalized hindlimb perfusion.
- Very small human sample (n=6 biopsies); invasive sural nerve biopsy limits recruitment and generalizability. - Retrospective tissue-based design with no matched blood samples, preventing integrated biomarker analysis. - The NOD.Aire⁻/⁻ model reflects broader autoimmunity (Aire deficiency), not pSS-specific pathology alone.
NETs and plasma cit-H3 may serve as biomarkers and therapeutic targets in pSS-PN; DNase I (dornase alfa) is already clinically approved, making NET-targeting a tractable strategy worth investigating in future pSS-PN trials.
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