Anti-Argonaute antibodies as a potential biomarker in NMOSD

Abstract

Background and objectivesNeuromyelitis optica spectrum disorders (NMOSDs) are a group of diseases mainly characterised by recurrent optic neuritis and/or myelitis. Most cases are associated with a pathogenic antibody against aquaporin-4 (AQP4-Ab), while some patients display autoantibodies targeting the myelin oligodendrocyte glycoprotein (myelin oligodendrocyte glycoprotein antibodies (MOG-Abs)). Anti-Argonaute antibodies (Ago-Abs) were first described in patients with rheumatological conditions and were recently reported as a potential biomarker in patients with neurological disorders. The aims of the study were to investigate if Ago-Abs can be detected in NMOSD and to evaluate its clinical usefulness.MethodsSera from patients prospectively referred to our centre with suspected NMOSD were tested for AQP4-Abs, MOG-Abs and Ago-Abs with cell-based assays.ResultsThe cohort included 104 prospective patients: 43 AQP4-Abs-positive cases, 34 MOG-Abs positive cases and 27 double-negative patients. Ago-Abs were detected in 7 of 104 patients (6.7%). Clinical data were available for six of seven patients. The median age at onset of patients with Ago-Abs was 37.5 [IQR 28.8–50.8]; five of six patients tested positive also for AQP4-Abs. Clinical presentation at onset was transverse myelitis in five patients, while one presented with diencephalic syndrome and experienced a transverse myelitis during follow-up. One case presented a concomitant polyradiculopathy. Median EDSS score at onset was 7.5 [IQR 4.8–8.4]; median follow-up was 40.3 months [IQR 8.3–64.7], and median EDSS score at last evaluation was 4.25 [IQR 1.9–5.5].ConclusionAgo-Abs are present in a subset of patients with NMOSD and, in some cases, represent the only biomarker of an autoimmune process. Their presence is associated with a myelitis phenotype and a severe disease course.

Case report: Overlap syndrome of neuromyelitis optica spectrum disorder with anti-Argonaute antibodies

“…AGO-Abs in patients with NMOSD could aid in the diagnosis, monitoring, and prediction of disease activity (12). A prospective study found that AGO-Abs were detected in 6.7% of patients with NMOSD, concluding that AGO-Abs could serve as a biomarker with high specificity and sensitivity for NMOSD (12). Notably, Moritz et al demonstrated that the ELISA method using an antigenstabilizing protocol is more sensitive compared with CBA, but with the same specificity (25).…”

“…This study demonstrated the coalesce of AGO-Abs in NMOSD. AGO-Abs in patients with NMOSD could aid in the diagnosis, monitoring, and prediction of disease activity ( 12 ). A prospective study found that AGO-Abs were detected in 6.7% of patients with NMOSD, concluding that AGO-Abs could serve as a biomarker with high specificity and sensitivity for NMOSD ( 12 ).…”

“…The pathophysiological role of AGO-Abs in patients with NMOSD presenting with myelitis remains unclear. AGO-Abs indicate a more severe clinical manifestation onset with a distinct phenotype of exclusively extensive transverse myelitis and prominent neurological impairment sequelae in NMOSD, sensory neuronopathies, several limbic encephalitis, and cerebellar syndrome ( 8 , 11 , 12 ). AGO proteins are cytoplasmic antigens, and the production of AGO-Abs immediately leads to a severe autoimmune inflammatory reaction ( 26 , 27 ).…”

“…These proteins are involved in the binding and degradation of specific RNA molecules, thereby influencing gene expression (7). AGO-Abs have the potential to identify novel biomarkers for diseases and have been identified in patients with systemic lupus erythematosus, scleroderma, dermatomyositis, and primary Sjögren's syndrome (pSS), revealing a link with system autoimmunity, sensory neuronopathies, limbic encephalitis, cerebellar syndrome, opsoclonus-myoclonus, length-dependent polyneuropathies (8)(9)(10)(11), and NMOSD (12).…”

Emerging trends and research foci of neuromyelitis optica spectrum disorder: a 20-year bibliometric analysis

“…After the discovery of anti-AQP4 as a serum marker, NMOSD was separated from MS as an independent disease (6). Since then, the number of publications on NMOSD has increased over the past year, and many articles (37)(38)(39)(40) have been published on its epidemiology, diagnosis, clinical characteristics, treatment regimens, treatment response, and outcomes. "Pathogenesis" was the keyword that burst for the longest time.…”