Evaluate and characterize clinical features and phenotypes of trisulfated-heparin-disaccharide (TS-HDS) and fibroblast-growth-factor-receptor-3 (FGFR3) antibody-associated neuropathy.

Autoantibodies, as a diagnostic biomarker, are increasingly being used, particularly in chronic inflammatory neuropathies (CINs); however, their role and associated clinical syndrome are not well defined.

Retrospective chart review. Ninety-two (92) patients were analyzed based on positive serologic testing (ELISA) for TS-HDS and FGFR3 antibodies.

Clinical characteristics were reported based on onset, symptomatology, sensory exam, history of cancer, antibody titers, serologic evaluation, electrodiagnostic study and nerve biopsy results.

Clinical characteristics: Sensory findings: Decreased distal sensation to pinprick (55.4%) and vibration (23.9%) was common, distal lower extremity paresthesia (41%), pain (30%) was the most common presenting symptom, (p-value 0.02). Pure sensory neuropathy was noted only in 3 TS-HDS and 4 FGFR3 patients; Motor findings: Unsteady gait (20.6%), distal lower extremity weakness was the most frequent motor finding. 

 Laboratory findings: Comprehensive neuropathy workup was essentially unrevealing. Fifteen patients were positive for both antibodies. Mean titer of TS-HDS was 72670 ± 127833 (normal <10,000) and for FGFR3 it was 9441.66 ± 6463 (normal <3,000). TS-HDS positive patients were comparatively younger (p-value <0.01). Nerve biopsies revealed demyelination in 2/2 TS-HDS and 4/5 FGFR3 patients. Nineteen patients had history of cancer (14 TS-HDS and 5 FGFR3). TS-HDS: basal cell carcinoma, carcinoid tumor, B-cell lymphoma with plasmocytoma and NHL. FGFR3L basal.

FGFR3 and TS-HDS antibodies appear not to be restricted to sensory neuropathy phenotype only, as previously described.

The pathogenic role of these biomarkers in chronic inflammatory neuropathies is not well established, and effectiveness of immunotherapy is still unclear. Further studies are warranted.