PT - JOURNAL ARTICLE AU - Le-Duy Do AU - Christian P. Moritz AU - Sergio Muñiz-Castrillo AU - Anne-Laurie Pinto AU - Yannick Tholance AU - Sabine Brugiere AU - Yohann Couté AU - Oda Stoevesandt AU - Michael J. Taussig AU - Véronique Rogemond AU - Alberto Vogrig AU - Bastien Joubert AU - Karine Ferraud AU - Jean-Philippe Camdessanché AU - Jean-Christophe Antoine AU - Jérôme Honnorat TI - Argonaute Autoantibodies as Biomarkers in Autoimmune Neurologic Diseases AID - 10.1212/NXI.0000000000001032 DP - 2021 Sep 01 TA - Neurology - Neuroimmunology Neuroinflammation PG - e1032 VI - 8 IP - 5 4099 - http://nn.neurology.org/content/8/5/e1032.short 4100 - http://nn.neurology.org/content/8/5/e1032.full SO - Neurol Neuroimmunol Neuroinflamm2021 Sep 01; 8 AB - Objective To identify and characterize autoantibodies (Abs) as novel biomarkers for an autoimmune context in patients with central and peripheral neurologic diseases.Methods Two distinct approaches (immunoprecipitation/mass spectrometry–based proteomics and protein microarrays) and patients' sera and CSF were used. The specificity of the identified target was confirmed by cell-based assay (CBA) in 856 control samples.Results Using the 2 methods as well as sera and CSF of patients with central and peripheral neurologic involvement, we identified Abs against the family of Argonaute proteins (mainly AGO1 and AGO2), which were already reported in systemic autoimmunity. AGO-Abs were mostly of immunoglobulin G 1 subclass and conformation dependent. Using CBA, AGO-Abs were detected in 21 patients with a high suspicion of autoimmune neurologic diseases (71.4% were women; median age 57 years) and only in 4/856 (0.5%) controls analyzed by CBA (1 diagnosed with small-cell lung cancer and the other 3 with Sjögren syndrome). Among the 21 neurologic patients identified, the main clinical presentations were sensory neuronopathy (8/21, 38.1%) and limbic encephalitis (6/21, 28.6%). Fourteen patients (66.7%) had autoimmune comorbidities and/or co-occurring Abs, whereas AGO-Abs were the only autoimmune biomarker for the remaining 7/21 (33.3%). Thirteen (61.9%) patients were treated with immunotherapy; 8/13 (61.5%) improved, and 3/13 (23.1%) remained stable, suggesting an efficacy of these treatments.Conclusions AGO-Abs might be potential biomarkers of autoimmunity in patients with central and peripheral nonparaneoplastic neurologic diseases. In 7 patients, AGO-Abs were the only biomarkers; thus, their identification may be useful to suspect the autoimmune character of the neurologic disorder.Classification of Evidence This study provides Class III evidence that AGO-Abs are more frequent in patients with autoimmune neurologic diseases than controls.Ab=autoantibody; AE=autoimmune encephalitis; CBA=cell-based assay; IgG=immunoglobulin G; LE=limbic encephalitis; mRS=modified Rankin Scale; MS=mass spectrometry; PNS=paraneoplastic neurologic syndrome; SCLC=small-cell lung cancer; SNN=sensory neuronopathy