Cytokine Signature Unveils Subgroups of Patients With Immune‐Mediated Sensory Neuronopathies

• Published in: Journal of the peripheral nervous system Vol. 30; no. 1; pp. e70008 - n/a
• Main Authors: Moritz, Christian P., Tholance, Yannick, Borowczyk, Coralie, Jospin, Fabienne, Paul, Stéphane, Antoine, Jean‐Christophe, Camdessanché, Jean‐Philippe
• Format: Journal Article
• Language: English
• Published: Malden, USA Wiley Periodicals, Inc 01.03.2025; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Antibodies; anti‐cytokine antibodies; Autoantibodies; Autoantibodies - blood; Autoimmune diseases; Autoimmune Diseases of the Nervous System - blood; Autoimmune Diseases of the Nervous System - immunology; Blood levels; cytokine signature; Cytokines; Cytokines - blood; Enzyme-linked immunosorbent assay; Female; Fibroblast growth factor receptors; Humans; Immunoreactivity; Inflammation; Interleukin 6; interleukins; Male; Middle Aged; Receptor, Fibroblast Growth Factor, Type 3 - immunology; Research Report; sensory neuronopathy; Sjogren's syndrome; Young Adult; cytokine signature; cytokines; anti‐cytokine antibodies; sensory neuronopathy; interleukins
• ISSN: 1085-9489; 1529-8027; 1529-8027
• DOI: 10.1111/jns.70008

ABSTRACT Background and Aims Immune‐mediated sensory neuronopathies (SNN) can occur alongside autoimmune disorders (e.g., Sjögren syndrome), involve autoantibodies (such as anti‐FGFR3 or anti‐AGO antibodies), or present in isolation. The underlying mechanisms remain unclear. This study aimed to investigate the role of proinflammatory cytokines in these conditions. Methods Blood levels of IL‐1β, IL‐6, IL‐17, TNF‐α, INF α‐2, and INF‐γ were measured using a Bioplex T200 platform and the Bio‐Plex Pro Reagent Kit III in 113 patients with SNN between 2.4 and 464.4 months after symptom onset, categorized based on disease course (acute, subacute, chronic). Eighteen patients had anti‐AGO antibodies, 48 had anti‐FGFR3 antibodies, and 14 had an autoimmune disease without detectable anti‐AGO or FGFR3 antibodies. Disease extent was measured by the SNN score, while the disease severity was evaluated using the modified Rankin score. Immunoreactivity against IL‐6 and INF‐γ was measured via ELISA. Results Multicomponent analysis utilizing cytokines levels identified four distinct patient subgroups characterized by differences in age at onset and SNN score. No significant differences were observed among the subgroups regarding disease course and severity, presence of anti‐AGO or anti‐FGFR3 antibodies, or association with an autoimmune disease. A small subgroup of three younger patients exhibited the highest levels of TNF‐α, IL‐6, and IL‐1β. Another subgroup of seven patients displayed elevated INF α‐2 levels and tended towards highest SNN scores. The largest group (95 subjects) comprised older individuals with relatively lower cytokine levels and decreased anti‐IL‐6 immunoreactivity. Interpretation These cytokine profiles suggest diverse underlying mechanisms within immune‐mediated SNN. Further investigation is warranted to determine whether certain profiles, particularly those involving young patients with elevated proinflammatory cytokines, might benefit from targeted treatments. We investigated cytokine levels in 113 patients with immune‐mediated sensory neuronopathies (SNN) with varied disease manifestations. We identified 4 patient subgroups based on cytokine profiles. One small subgroup had high TNF‐α, IL‐6, and IL‐1β and was younger. Findings suggest different SNN mechanisms, which might be a potential for targeted treatments.