BRIEF RESEARCH REPORT article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1604456
This article is part of the Research TopicNovel Biomarkers for Early Diagnosis, involved in Autoimmune and Autoinflammatory DiseasesView all 17 articles
Inter-laboratory comparison of a serum Fibroblast Growth Factor Receptor 3 (FGFR3) antibody test in sensory neuropathies
Provisionally accepted
Luise Appeltshauser1*
Christian Moritz2
Lena Reinhardt1
Luisa Kreß1
Nurcan Üçeyler1
François Lassablière2Anastasia Barcic1
Sabine Seefried1
Claudia Sommer1
Yannick Tholance3
Jean-Christophe Antoine4
Jean-Philippe Camdessanche4
Kathrin Doppler1- 1University Hospital Würzburg, Würzburg, Germany
- 2Synaptopathies et autoanticorps (SynatAc), Institut MELIS-NeuroMyoGène, INSERM U1314/CNRS UMR 5284, Université Jean Monnet, Saint-Étienne, France
- 3Department of Biochemistry, CHU Saint-Etienne, Saint-Etienne, France
- 4Department of Neurology, CHU Saint-Etienne, Saint-Etienne, France
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Introduction: Autoantibodies against fibroblast growth factor receptor 3 (FGFR3) have been suggested as a diagnostic marker in both sensory large and small fiber neuropathy. Yet, their clinical relevance remains unclear and no standardized protocols for antibody testing exist. Here, we evaluate an anti-FGFR3 ELISA protocol in an inter-laboratory comparison. Methods: We performed anti-FGFR3 ELISA on 42 serum samples of patients with sensory neuronopathy (n = 18), small fiber neuropathy (n = 18), and healthy controls (n = 6) in two independent centers in France (center 1) and Germany (center 2) using identical protocols, with double immunofluorescence staining on rat dorsal root ganglion (DRG) sections as a confirmational test. Results: Overall ELISA concordance was 34/42 (81.0%, Cohen's kappa = 0.61, substantial agreement). Discordance occurred for sera with optical densities (OD) near the cut-off. ODs correlated (r = 0.68, p < 0.0001), but were lower at center 2 (median = 0.076 vs 0.293, p < 0.0001), indicating that cut-off values are laboratory-specific. 11/16 (68.8%) ELISA-double-positive sera stained small DRG neurons, colocalizing with commercial anti-FGFR3 antibody, while positive binding was only found in 1/20 (5%) of ELISA-negative sera (p < 0.0001). DRG-positive samples showed higher ODs than negative ones (p < 0.0001). Discussion: We provide and evaluate a detailed ELISA protocol for anti-FGFR3 diagnostic assessment. Positive results near the threshold should be interpreted cautiously. Anti-FGFR3 DRG staining may be a useful confirmatory method and could increase diagnostic specificity. This study facilitates future studies on the diagnostic relevance of anti-FGFR3 autoantibodies in sensory neuropathies.
Keywords: Fibroblast growth factor receptor 3, ELISA, Autoantibodies, sensory neuropathy, Sensory neuronopathy, Small fiber neuropathy, dorsal root ganglia
Received: 01 Apr 2025; Accepted: 23 Sep 2025.
Copyright: © 2025 Appeltshauser, Moritz, Reinhardt, Kreß, Üçeyler, Lassablière, Barcic, Seefried, Sommer, Tholance, Antoine, Camdessanche and Doppler. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Luise Appeltshauser, appeltshau_l@ukw.de
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