Serum autoantibodies against α7-nicotinic receptors in subgroups of patients with bipolar disorder or schizophrenia: clinical features and link with peripheral inflammation
Abstract There is growing evidence that autoantibodies (AAbs) against proteins expressed in the brain are playing an important role in neurological and psychiatric disorders. Here, we explore the presence and the role of peripheral AAbs to the α7-nicotinic acetylcholine receptor (nAChR) in inflammat...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-03-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-024-02853-8 |
| _version_ | 1797259036589031424 |
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| author | Estelle Darrau Elise Jacquemet Stéphanie Pons Laurène Schlick Marios Zouridakis Ching-Lien Wu Jean-Romain Richard Caroline Barau Philippe Le Corvoisier Robert Yolken Ryad Tamouza Marion Leboyer Uwe Maskos |
| author_facet | Estelle Darrau Elise Jacquemet Stéphanie Pons Laurène Schlick Marios Zouridakis Ching-Lien Wu Jean-Romain Richard Caroline Barau Philippe Le Corvoisier Robert Yolken Ryad Tamouza Marion Leboyer Uwe Maskos |
| author_sort | Estelle Darrau |
| collection | DOAJ |
| description | Abstract There is growing evidence that autoantibodies (AAbs) against proteins expressed in the brain are playing an important role in neurological and psychiatric disorders. Here, we explore the presence and the role of peripheral AAbs to the α7-nicotinic acetylcholine receptor (nAChR) in inflammatory subgroups of psychiatric patients with bipolar disorder (BD) or schizophrenia (SCZ) and healthy controls. We have identified a continuum of AAb levels in serum when employing a novel ELISA technique, with a significant elevation in patients compared to controls. Using unsupervised two-step clustering to stratify all the subjects according to their immuno-inflammatory background, we delineate one subgroup consisting solely of psychiatric patients with severe symptoms, high inflammatory profile, and significantly increased levels of anti-nAChR AAbs. In this context, we have used monoclonal mouse anti-human α7-nAChR antibodies (α7-nAChR-mAbs) and shown that TNF-α release was enhanced upon LPS stimulation in macrophages pre-incubated with α7-nAChR-mAbs compared to the use of an isotype control. These findings provide a basis for further study of circulating nicotinic AAbs, and the inflammatory profile observed in patients with major mood and psychotic disorders. |
| first_indexed | 2024-04-24T23:03:03Z |
| format | Article |
| id | doaj.art-d70c930053cb4950802636999a6aa666 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-24T23:03:03Z |
| publishDate | 2024-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-d70c930053cb4950802636999a6aa6662024-03-17T12:39:06ZengNature Publishing GroupTranslational Psychiatry2158-31882024-03-0114111310.1038/s41398-024-02853-8Serum autoantibodies against α7-nicotinic receptors in subgroups of patients with bipolar disorder or schizophrenia: clinical features and link with peripheral inflammationEstelle Darrau0Elise Jacquemet1Stéphanie Pons2Laurène Schlick3Marios Zouridakis4Ching-Lien Wu5Jean-Romain Richard6Caroline Barau7Philippe Le Corvoisier8Robert Yolken9Ryad Tamouza10Marion Leboyer11Uwe Maskos12Université Paris Est Créteil, INSERM U955, IMRB, Translational NeuroPsychiatry LaboratoryInstitut Pasteur, Université de Paris Cité, Bioinformatics and Biostatistics HubInstitut Pasteur, Université de Paris Cité, Integrative Neurobiology of Cholinergic Systems, CNRS UMR 3571Institut Pasteur, Université de Paris Cité, Integrative Neurobiology of Cholinergic Systems, CNRS UMR 3571Laboratory of Molecular Neurobiology and Immunology, Hellenic Pasteur InstituteUniversité Paris Est Créteil, INSERM U955, IMRB, Translational NeuroPsychiatry LaboratoryUniversité Paris Est Créteil, INSERM U955, IMRB, Translational NeuroPsychiatry LaboratoryPlateforme de ressources biologiques, Hôpital Henri Mondor, Université Paris Est CréteilCentre d’Investigation Clinique 1430, AP-HP, Hôpital Henri Mondor, Université Paris Est CréteilStanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins School of MedicineUniversité Paris Est Créteil, INSERM U955, IMRB, Translational NeuroPsychiatry LaboratoryUniversité Paris Est Créteil, INSERM U955, IMRB, Translational NeuroPsychiatry LaboratoryInstitut Pasteur, Université de Paris Cité, Integrative Neurobiology of Cholinergic Systems, CNRS UMR 3571Abstract There is growing evidence that autoantibodies (AAbs) against proteins expressed in the brain are playing an important role in neurological and psychiatric disorders. Here, we explore the presence and the role of peripheral AAbs to the α7-nicotinic acetylcholine receptor (nAChR) in inflammatory subgroups of psychiatric patients with bipolar disorder (BD) or schizophrenia (SCZ) and healthy controls. We have identified a continuum of AAb levels in serum when employing a novel ELISA technique, with a significant elevation in patients compared to controls. Using unsupervised two-step clustering to stratify all the subjects according to their immuno-inflammatory background, we delineate one subgroup consisting solely of psychiatric patients with severe symptoms, high inflammatory profile, and significantly increased levels of anti-nAChR AAbs. In this context, we have used monoclonal mouse anti-human α7-nAChR antibodies (α7-nAChR-mAbs) and shown that TNF-α release was enhanced upon LPS stimulation in macrophages pre-incubated with α7-nAChR-mAbs compared to the use of an isotype control. These findings provide a basis for further study of circulating nicotinic AAbs, and the inflammatory profile observed in patients with major mood and psychotic disorders.https://doi.org/10.1038/s41398-024-02853-8 |
| spellingShingle | Estelle Darrau Elise Jacquemet Stéphanie Pons Laurène Schlick Marios Zouridakis Ching-Lien Wu Jean-Romain Richard Caroline Barau Philippe Le Corvoisier Robert Yolken Ryad Tamouza Marion Leboyer Uwe Maskos Serum autoantibodies against α7-nicotinic receptors in subgroups of patients with bipolar disorder or schizophrenia: clinical features and link with peripheral inflammation Translational Psychiatry |
| title | Serum autoantibodies against α7-nicotinic receptors in subgroups of patients with bipolar disorder or schizophrenia: clinical features and link with peripheral inflammation |
| title_full | Serum autoantibodies against α7-nicotinic receptors in subgroups of patients with bipolar disorder or schizophrenia: clinical features and link with peripheral inflammation |
| title_fullStr | Serum autoantibodies against α7-nicotinic receptors in subgroups of patients with bipolar disorder or schizophrenia: clinical features and link with peripheral inflammation |
| title_full_unstemmed | Serum autoantibodies against α7-nicotinic receptors in subgroups of patients with bipolar disorder or schizophrenia: clinical features and link with peripheral inflammation |
| title_short | Serum autoantibodies against α7-nicotinic receptors in subgroups of patients with bipolar disorder or schizophrenia: clinical features and link with peripheral inflammation |
| title_sort | serum autoantibodies against α7 nicotinic receptors in subgroups of patients with bipolar disorder or schizophrenia clinical features and link with peripheral inflammation |
| url | https://doi.org/10.1038/s41398-024-02853-8 |
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