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

## TL;DR

This study identifies four distinct patient subgroups in immune-mediated sensory neuronopathies based on cytokine profiles, suggesting different underlying mechanisms and potential for targeted treatments.

## Contribution

The study introduces a cytokine-based classification of immune-mediated sensory neuronopathy patients, revealing distinct subgroups with potential implications for treatment.

## Key findings

- Four distinct patient subgroups were identified based on cytokine profiles and age at onset.
- A subgroup of younger patients showed elevated levels of TNF-α, IL-6, and IL-1β.
- Another subgroup had elevated INF α-2 levels and higher SNN scores.

## Abstract

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.

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.

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.

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.