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FGFR3 autoantibodies in sensory neuronopathy
  1. Norman Latov
  1. Department of Neurology, Weill Medical College of Cornell University, New York, New York, USA
  1. Correspondence to Dr Norman Latov, Weill Medical College of Cornell University, New York, NY 10022, USA; nol2002{at}


FGFR3 antibodies have been associated with sensory neuropathy, but many questions remain regarding their use in clinical practice.

  • neuropathy
  • immunology
  • neuroimmunology
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In the paper by Tholance and colleagues,1 the authors expand on their studies of anti-FGFR3 antibodies. They report that subjects in both European and Brazilian centres exhibit a predominately non-length dependent phenotype, consistent with sensory neuronopathy.

Sensory neuronopathy present a challenging clinical problem.2 Immune mechanisms are suspected given its association with Sjogren syndrome, celiac disease, paraneoplastic anti-HU and CRMP5 antibodies, or rare pathological studies showing inflammatory dorsal root ganglia (DRG) infiltrates. However, it can also occur in non-inflammatory conditions such as Fabry disease or B6 and cisplatin toxicities, and DRGs can harbour viruses such as Varicella zoster or HIV-1. In approximately 50% of patients, no cause can be identified, and the physician has to decide on whether to recommend a trial of immune therapy, especially if the neuropathy is progressive, even if the cause is uncertain. In such cases, anti-FGFR3 antibodies may be a marker for autoimmunity.

The authors are to be commended on their research, and congratulated on their discovery of anti-FGFR3 antibodies. Many questions remain however. The association with purely sensory neuropathy, as example, is based on only a single study from their group,3 and needs to be confirmed by others, to eliminate the possibility of bias. An opportunity was missed by not also testing patients with sensorimotor or motor neuropathies for anti-FGFR3 antibodies in the current study. The absence of motor involvement needs to be explained, as FGFR3 is also present at motor nerve terminals, where it functions as a receptor for botulinum toxins.4

The disease mechanism also presents a challenge. The antibodies bind to intracellular regions in FGFR3, so if they are not pathogenic or taken up by DRGs, then other mechanism, such as T-cell reactivity to FGFR3, or an associated or cross-reactive antigen, would have to be considered. Such T-cell reactivity could also explain the observed multifocal distribution, IgG class switching, or absence of reactivity to the extracellular region FGRF3. Answers to these questions would have to await further pathological and immunological investigations, and the development of experimental animal models for the disease.

A more clinically relevant concern, is whether the anti-GFR3 antibodies can identify patients that would respond to immune intervention. The mechanisms themselves are of less immediate concern, other than to possibly inform regarding the likelihood of response to particular therapies. These issues would have to be addressed in prospective clinical trials.


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  • Funding The author has not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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