Argonaute Autoantibodies as Biomarkers in Autoimmune Neurologic Diseases

Do, Le-Duy; Moritz, Christian P.; Muñiz‐Castrillo, Sergio; Pinto, Anne‐Laurie; Tholance, Yannick; Brugière, Sabine; Couté, Yohann; Stoevesandt, Oda; Taussig, Michael J.; Rogemond, Véronique; Vogrig, Alberto; Joubert, Bastien; Férraud, Karine; Camdessanché, Jean‐Philippe; Antoine, Jean‐Christophe; Honnorat, Jérôme

doi:10.1212/nxi.0000000000001032

Cited by 20 publications

(33 citation statements)

References 30 publications

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“…Antibodies with rather non-conformational epitopes do not or not significantly lose their reactivity upon antigen linearization, such as the commercial anti-AGO1 antibody and a subgroup (here: subgroup-3) of AGO1 Abspositive patients. Using this approach, all 14 tested patients from our first study bound a conformational epitope, which confirms our first suspicion, where denatured (Western blot) or truncated (one spot of the protein arrays) AGO proteins were not or less useful to detect these antibodies (8).…”

Section: Of Disease Repartition Antibody Titers and Igg Subclasses Be...supporting

confidence: 74%

“…As patient antibodies appear to predominantly bind the native AGO proteins, immunoprecipitation has initially been considered the only method to reliably detect anti-Su/Ago2 antibodies (9). Nevertheless, while we confirmed that denatured (Western blot) or truncated AGO proteins were not useful to detect these antibodies, our recently established CBA appeared reliable to detect the native antigen (8). Here, we established a sensitive ELISA approach which we applied to estimate the frequency of AGO1 in NP and AID and to determine sensitivity differences between AGO1 and AGO2 Abs.…”

Section: Of Disease Repartition Antibody Titers and Igg Subclasses Be...mentioning

confidence: 81%

“…ELISA for AGO1 vs. AGO2 comparison, screening of the different disease cohorts, and IgG subclass identification For 1) comparing AGO1 vs. AGO2 signals in the fourteen patients recently reported AGO1/AGO2 Abs-positive in CBA (8), 2) screening the larger disease cohorts, and 3) IgG subclass detection, we applied the conformation-stabilizing coating version (with glycerol) and our previously reported ELISA design (13,14) using AGO1 as the antigen and the above described ELISA protocol.…”

Section: Establishment Of a Comparative Denaturing/stabilizing Elisa ...mentioning

confidence: 99%

“…AGO2 Abs have been reported in the serum of patients with systemic lupus erythematosus (SLE), scleroderma, Sjögren syndrome (SjS), and other rheumatologic autoimmune diseases ( 9 ). In our previous study, 67% of AGO Abs-positive patients had an associated systemic autoimmune disease and importantly, 62% improved with immunomodulatory treatments showing the potential importance of detecting AGO antibodies in certain neurological diseases ( 8 ). We concluded that AGO Abs might be potential biomarkers of an autoimmunity context in patients with central and peripheral neurologic disease, which might help predicting the treatment response.…”

Section: Introductionmentioning

confidence: 96%

“…We recently used CBA for the detection of anti-argonaute (AGO) Abs in neurological diseases. Twenty-one patients reacting with AGO1 and 2 were identified who had different neurological syndromes among which limbic encephalitis and sensory neuronopathy were the most frequent ( 8 ). AGO2 Abs have been reported in the serum of patients with systemic lupus erythematosus (SLE), scleroderma, Sjögren syndrome (SjS), and other rheumatologic autoimmune diseases ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

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Conformation-stabilizing ELISA and cell-based assays reveal patient subgroups targeting three different epitopes of AGO1 antibodies

Moritz

Tholance

et al. 2022

Front. Immunol.

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Autoantibodies (Abs) are biomarkers for many disease conditions and are increasingly used to facilitate diagnosis and treatment decisions. To guarantee high sensitivity and specificity, the choice of their detection method is crucial. Via cell-based assays, we recently found 21 patients with neurological diseases positive for antibodies against argonaute (AGO), 10 of which having a neuropathy (NP). Here, we established a simple and conformation-sensitive ELISA with the aim to distinguish between AGO1 Abs against conformational epitopes and non-conformational epitopes and to reveal further characteristics of AGO1 antibodies in NP and autoimmune disease (AID). In a retrospective multicenter case/control and observational study, we tested 434 patients with NP, 274 disease controls with AID, and 116 healthy controls (HC) for AGO1 Abs via conformation-stabilizing ELISA. Seropositive patients were also tested for conformation-specificity via comparative denaturing/stabilizing ELISA (CODES-ELISA), CBA positivity, AGO1 titers and IgG subclasses, and AGO2 reactivity. These parameters were statistically compared among different epitope-specific patient groups. We found Abs in 44 patients, including 28/434 (6.5%) NP, 16/274 (5.8%) AID, and 0/116 (0%) HC. Serum reactivity was consistently higher for AGO1 than AGO2. Globally among the 44 AGO1 Abs-positive patients, 42 were also tested in CBA for AGO1 Abs positivity and 15 (35.7%) were positive. Furthermore, 43 were tested for conformation-specificity and 32 (74.4%) bound a conformational epitope. Among the subgroups of highly positive patients (ELISA z-score >14) with sera binding conformational epitopes (n=23), 14 patient sera were also CBA positive and 9 bound a second conformational but CBA-inaccessible epitope. A third, non-conformational epitope was bound by 11/43 (15.6%). Among the epitope-specific patient subgroups, we found significant differences regarding the Abs titers, IgG subclass, and AGO2 reactivity. When comparing AGO1 Abs-positive NP versus AID patients, we found the conformation-specific and CBA inaccessible epitope significantly more frequently in AID patients. We conclude that 1) conformational ELISA was more sensitive than CBA in detecting AGO1 Abs, 2) serum reactivity is higher for AGO1 than for AGO2 at least for NP patients, 3) AGO1 Abs might be a marker-of-interest in 6.5% of NP patients, 4) distinguishing epitopes might help finding different patient subgroups.

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Section: Of Disease Repartition Antibody Titers and Igg Subclasses Be...supporting

confidence: 74%

Section: Of Disease Repartition Antibody Titers and Igg Subclasses Be...mentioning

confidence: 81%

Section: Establishment Of a Comparative Denaturing/stabilizing Elisa ...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Conformation-stabilizing ELISA and cell-based assays reveal patient subgroups targeting three different epitopes of AGO1 antibodies

Moritz

Tholance

et al. 2022

Front. Immunol.

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Autoimmune encephalitis: what the radiologist needs to know

Sanvito,

Pichiecchio,

Paoletti

et al. 2024

Neuroradiology

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Autoimmune encephalitis is a relatively novel nosological entity characterized by an immune-mediated damage of the central nervous system. While originally described as a paraneoplastic inflammatory phenomenon affecting limbic structures, numerous instances of non-paraneoplastic pathogenesis, as well as extra-limbic involvement, have been characterized. Given the wide spectrum of insidious clinical presentations ranging from cognitive impairment to psychiatric symptoms or seizures, it is crucial to raise awareness about this disease category. In fact, an early diagnosis can be dramatically beneficial for the prognosis both to achieve an early therapeutic intervention and to detect a potential underlying malignancy. In this scenario, the radiologist can be the first to pose the hypothesis of autoimmune encephalitis and refer the patient to a comprehensive diagnostic work-up – including clinical, serological, and neurophysiological assessments.In this article, we illustrate the main radiological characteristics of autoimmune encephalitis and its subtypes, including the typical limbic presentation, the features of extra-limbic involvement, and also peculiar imaging findings. In addition, we review the most relevant alternative diagnoses that should be considered, ranging from other encephalitides to neoplasms, vascular conditions, and post-seizure alterations. Finally, we discuss the most appropriate imaging diagnostic work-up, also proposing a suggested MRI protocol.

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Peripheral nervous system involvement accompanies central nervous system involvement in anti-glial fibrillary acidic protein (GFAP) antibody-related disease

Theuriet,

Cluse,

Gravier-Dumonceau

et al. 2023

J Neurol

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Background Glial fibrillary acidic protein (GFAP) is expressed by astrocytes in the central nervous system (CNS), but also by immature and regenerative Schwann cells in the peripheral nervous system (PNS). GFAP antibodies (GFAP-Abs) in cerebrospinal fluid (CSF) have been mainly described in patients with meningoencephalomyelitis. We aimed to study PNS symptoms in patients with CSF GFAP-Abs. Methods We retrospectively included all patients tested positive for GFAP-Abs in the CSF by immunohistochemistry and confirmed by cell-based assay expressing human GFAPα since 2017, from two French reference centers. Results In a cohort of 103 CSF GFAP-Abs patients, 25 (24%) presented with PNS involvement. Among them, the median age at onset was 48 years and 14/25 (56%) were female. Abnormal electroneuromyography was observed in 11/25 patients (44%), including eight isolated radiculopathies, one radiculopathy associated with polyneuropathy, one radiculopathy associated with sensory neuronopathy, and one demyelinating polyradiculoneuropathy. Cranial nerve involvement was observed in 18/25 patients (72%). All patients except one had an associated CNS involvement. The first manifestation of the disease concerned the PNS in three patients. First-line immunotherapy was administered to 18/24 patients (75%). The last follow-up modified Rankin Scale was ≤ 2 in 19/23 patients (83%). Patients with PNS involvement had significantly more bladder dysfunction than patients with isolated CNS involvement (68 vs 40.3%, p = 0.031). Conclusions PNS involvement in GFAP-Abs autoimmunity is heterogeneous but not rare and is mostly represented by acute or subacute cranial nerve injury and/or lower limb radiculopathy. Rarely, PNS involvement can be the first manifestation revealing the disease.

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Argonaute Autoantibodies as Biomarkers in Autoimmune Neurologic Diseases

Cited by 20 publications

References 30 publications

Conformation-stabilizing ELISA and cell-based assays reveal patient subgroups targeting three different epitopes of AGO1 antibodies

Conformation-stabilizing ELISA and cell-based assays reveal patient subgroups targeting three different epitopes of AGO1 antibodies

Autoimmune encephalitis: what the radiologist needs to know

Peripheral nervous system involvement accompanies central nervous system involvement in anti-glial fibrillary acidic protein (GFAP) antibody-related disease

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