RT Journal Article
SR Electronic
T1 Argonaute Autoantibodies as Biomarkers in Autoimmune Neurologic Diseases
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e1032
DO 10.1212/NXI.0000000000001032
VO 8
IS 5
A1 Le-Duy Do
A1 Christian P. Moritz
A1 Sergio Muñiz-Castrillo
A1 Anne-Laurie Pinto
A1 Yannick Tholance
A1 Sabine Brugiere
A1 Yohann Couté
A1 Oda Stoevesandt
A1 Michael J. Taussig
A1 Véronique Rogemond
A1 Alberto Vogrig
A1 Bastien Joubert
A1 Karine Ferraud
A1 Jean-Philippe Camdessanché
A1 Jean-Christophe Antoine
A1 Jérôme Honnorat
YR 2021
UL http://nn.neurology.org/content/8/5/e1032.abstract
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