ArticleFrontiers in immunology2025
Inter-laboratory comparison of a serum fibroblast growth factor receptor 3 (FGFR3) antibody test in sensory neuropathies.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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.
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