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