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BACKGROUND: To investigate Ranvier's autoantibodies prevalence and isotypes in various peripheral neuropathy variants, compare clinical features between seronegative and seropositive patients, and elucidate immune mechanisms underlying antibody generation. METHODS: Antibodies against anti-neurofascin-155 (NF155), NF186, contactin-1 (CNTN1), CNTN2, contactin-associated protein 1 (CASPR1), and CASPR2 were identified through cell-based assays. Plasma cytokines were analyzed in anti-NF155 antibody-positive chronic inflammatory demyelinating polyneuropathy (NF155+ CIDP) and Ranvier's antibodies-negative CIDP (Ab- CIDP) patients using a multiplexed fluorescent immunoassay, validated in vitro in a cell culture model. RESULTS: In 368 plasma samples, 50 Ranvier's autoantibodies were found in 45 individuals, primarily in CIDP cases (25 out of 69 patients) and in 10 out of 122 Guillain-Barré syndrome patients. Anti-NF155 and CNTN1-IgG were exclusive to CIDP. Fourteen samples were NF155-IgG, primarily IgG4 subclass, linked to CIDP features including early onset, tremor, sensory disturbance, elevated CSF protein, prolonged motor latency, conduction block, and poor treatment response. NF155-IgG had low sensitivity (20.28%) but high specificity (100%) for CIDP, rising to 88.88% with tremor and prolonged motor latency. Cytokine profiling in NF155+ CIDP revealed distinct immune responses involving helper T cells, toll-like receptor pathways. Some NF155+ CIDP patients had circulating NF155-specific B cells producing NF155-IgG without antigen presence, suggesting therapeutic potential. CONCLUSION: The study emphasizes the high specificity and sensitivity of NF155-IgG for diagnosing CIDP characterized by distinctive features. Further investigation into circulating NF155-specific B cell phenotypes may pave the way for B cell directed therapy.
RESUMEN
Objective: This study aimed to determine the diagnostic efficiency of a novel immunoblotting detection assay for anti-ganglioside antibodies (AGAs) in the Guillain-Barre syndrome (GBS). Method: Serum immunoglobulin (IgG and IgM) of AGAs were measured in 121 participants from a registered cohort study of immune-mediated neuropathies and 29 healthy controls by immunoblotting panel assay. Sensitivity, specificity, and positive predictive value (PPV) of the assay were compared to calculate the diagnostic accuracy. Result: In our cohort, any of the AGAs were positive in 42.4% of the GBS patients. The sensitivity and specificity of AGAs (both IgG and IgM) in the diagnosis of GSB were 42 and 76% while for IgG-AGAs were 35 and 87%. AGAs positivity had a significant association with the AMAN subtype (P = 0.0004), and the sensitivity, specificity of AGAs in AMAN were 86, 69%, respectively with high (AUC = 0.78, p = 0.002) discriminative powers. GM1-IgG AGA was more common and specific to AMAN patients than other GBS forms (p = 0.008). Conclusion: Our novel immunoblotting detection assay could complement GBS diagnosis. IgG-AGAs were more likely to be detected in GBS, and GM1-IgG AGA could assist AMAN diagnosis.
