Inositol 1,4,5-trisphosphate receptor type 1 autoantibody (ITPR1-IgG/anti-Sj)-associated autoimmune cerebellar ataxia, encephalitis and peripheral neuropathy: review of the literature
Abstract Background In 2014, we first described novel autoantibodies to the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1-IgG/anti-Sj) in patients with autoimmune cerebellar ataxia (ACA) in this journal. Here, we provide a review of the available literature on ITPR1-IgG/anti-Sj, covering clini...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-022-02545-4 |
| _version_ | 1811223022676213760 |
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| author | Sven Jarius Stefan Bräuninger Ha-Yeun Chung Christian Geis Jürgen Haas Lars Komorowski Brigitte Wildemann Christian Roth |
| author_facet | Sven Jarius Stefan Bräuninger Ha-Yeun Chung Christian Geis Jürgen Haas Lars Komorowski Brigitte Wildemann Christian Roth |
| author_sort | Sven Jarius |
| collection | DOAJ |
| description | Abstract Background In 2014, we first described novel autoantibodies to the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1-IgG/anti-Sj) in patients with autoimmune cerebellar ataxia (ACA) in this journal. Here, we provide a review of the available literature on ITPR1-IgG/anti-Sj, covering clinical and paraclinical presentation, tumour association, serological findings, and immunopathogenesis. Methods Review of the peer-reviewed and PubMed-listed English language literature on ITPR1-IgG/anti-Sj. In addition, we provide an illustrative report on a new patient with ITPR1-IgG-associated encephalitis with cognitive decline and psychosis. Results So far, at least 31 patients with serum ITPR1-IgG/anti-Sj have been identified (clinical information available for 21). The most common manifestations were ACA, encephalopathy with seizures, myelopathy, and (radiculo)neuropathy, including autonomic neuropathy. In 45% of cases, an underlying tumour was present, making the condition a facultative paraneoplastic neurological disorder. The neurological syndrome preceded tumour diagnosis in all but one case. In most cases, immunotherapy had only moderate or no effect. The association of ITPR1-IgG/anti-Sj with manifestations other than ACA is corroborated by the case of a 48-year-old woman with high-titre ITPR1-IgG/anti-Sj antibodies and rapid cognitive decline, affecting memory, attention and executive function, and psychotic manifestations, including hallucinations, investigated here in detail. FDG-PET revealed right-temporal glucose hypermetabolism compatible with limbic encephalitis. Interestingly, ITPR1-IgG/anti-Sj mainly belonged to the IgG2 subclass in both serum and cerebrospinal fluid (CSF) in this and further patients, while it was predominantly IgG1 in other patients, including those with more severe outcome, and remained detectable over the entire course of disease. Immunotherapy with intravenous methylprednisolone, plasma exchange, and intravenous immunoglobulins, was repeatedly followed by partial or complete recovery. Long-term treatment with cyclophosphamide was paralleled by relative stabilization, although the patient noted clinical worsening at the end of each treatment cycle. Conclusions The spectrum of neurological manifestations associated with ITPR1 autoimmunity is broader than initially thought. Immunotherapy may be effective in some cases. Studies evaluating the frequency of ITPR1-IgG/anti-Sj in patients with cognitive decline and/or psychosis of unknown aetiology are warranted. Tumour screening is essential in patients presenting with ITPR1-IgG/anti-Sj. |
| first_indexed | 2024-04-12T08:25:47Z |
| format | Article |
| id | doaj.art-cbb82a9ccc5c4e6bb3a035c95dd5eb32 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-12T08:25:47Z |
| publishDate | 2022-07-01 |
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| spelling | doaj.art-cbb82a9ccc5c4e6bb3a035c95dd5eb322022-12-22T03:40:24ZengBMCJournal of Neuroinflammation1742-20942022-07-0119112110.1186/s12974-022-02545-4Inositol 1,4,5-trisphosphate receptor type 1 autoantibody (ITPR1-IgG/anti-Sj)-associated autoimmune cerebellar ataxia, encephalitis and peripheral neuropathy: review of the literatureSven Jarius0Stefan Bräuninger1Ha-Yeun Chung2Christian Geis3Jürgen Haas4Lars Komorowski5Brigitte Wildemann6Christian Roth7Molecular Neuroimmunology Group, Department of Neurology, University of HeidelbergDepartment of Neurology, DRK-Kliniken NordhessenSection Translational Neuroimmunology, Department of Neurology, Jena University HospitalSection Translational Neuroimmunology, Department of Neurology, Jena University HospitalMolecular Neuroimmunology Group, Department of Neurology, University of HeidelbergInstitute for Experimental Immunology, affiliated to EUROIMMUN Medizinische Labordiagnostika AGMolecular Neuroimmunology Group, Department of Neurology, University of HeidelbergDepartment of Neurology, DRK-Kliniken NordhessenAbstract Background In 2014, we first described novel autoantibodies to the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1-IgG/anti-Sj) in patients with autoimmune cerebellar ataxia (ACA) in this journal. Here, we provide a review of the available literature on ITPR1-IgG/anti-Sj, covering clinical and paraclinical presentation, tumour association, serological findings, and immunopathogenesis. Methods Review of the peer-reviewed and PubMed-listed English language literature on ITPR1-IgG/anti-Sj. In addition, we provide an illustrative report on a new patient with ITPR1-IgG-associated encephalitis with cognitive decline and psychosis. Results So far, at least 31 patients with serum ITPR1-IgG/anti-Sj have been identified (clinical information available for 21). The most common manifestations were ACA, encephalopathy with seizures, myelopathy, and (radiculo)neuropathy, including autonomic neuropathy. In 45% of cases, an underlying tumour was present, making the condition a facultative paraneoplastic neurological disorder. The neurological syndrome preceded tumour diagnosis in all but one case. In most cases, immunotherapy had only moderate or no effect. The association of ITPR1-IgG/anti-Sj with manifestations other than ACA is corroborated by the case of a 48-year-old woman with high-titre ITPR1-IgG/anti-Sj antibodies and rapid cognitive decline, affecting memory, attention and executive function, and psychotic manifestations, including hallucinations, investigated here in detail. FDG-PET revealed right-temporal glucose hypermetabolism compatible with limbic encephalitis. Interestingly, ITPR1-IgG/anti-Sj mainly belonged to the IgG2 subclass in both serum and cerebrospinal fluid (CSF) in this and further patients, while it was predominantly IgG1 in other patients, including those with more severe outcome, and remained detectable over the entire course of disease. Immunotherapy with intravenous methylprednisolone, plasma exchange, and intravenous immunoglobulins, was repeatedly followed by partial or complete recovery. Long-term treatment with cyclophosphamide was paralleled by relative stabilization, although the patient noted clinical worsening at the end of each treatment cycle. Conclusions The spectrum of neurological manifestations associated with ITPR1 autoimmunity is broader than initially thought. Immunotherapy may be effective in some cases. Studies evaluating the frequency of ITPR1-IgG/anti-Sj in patients with cognitive decline and/or psychosis of unknown aetiology are warranted. Tumour screening is essential in patients presenting with ITPR1-IgG/anti-Sj.https://doi.org/10.1186/s12974-022-02545-4Anti-neuronal autoantibodiesInositol 1,4,5-trisphosphate receptor type 1 antibodies (ITPR1-IgG)Anti-SjAutoimmune encephalitisParaneoplastic neurological syndromesDementia |
| spellingShingle | Sven Jarius Stefan Bräuninger Ha-Yeun Chung Christian Geis Jürgen Haas Lars Komorowski Brigitte Wildemann Christian Roth Inositol 1,4,5-trisphosphate receptor type 1 autoantibody (ITPR1-IgG/anti-Sj)-associated autoimmune cerebellar ataxia, encephalitis and peripheral neuropathy: review of the literature Journal of Neuroinflammation Anti-neuronal autoantibodies Inositol 1,4,5-trisphosphate receptor type 1 antibodies (ITPR1-IgG) Anti-Sj Autoimmune encephalitis Paraneoplastic neurological syndromes Dementia |
| title | Inositol 1,4,5-trisphosphate receptor type 1 autoantibody (ITPR1-IgG/anti-Sj)-associated autoimmune cerebellar ataxia, encephalitis and peripheral neuropathy: review of the literature |
| title_full | Inositol 1,4,5-trisphosphate receptor type 1 autoantibody (ITPR1-IgG/anti-Sj)-associated autoimmune cerebellar ataxia, encephalitis and peripheral neuropathy: review of the literature |
| title_fullStr | Inositol 1,4,5-trisphosphate receptor type 1 autoantibody (ITPR1-IgG/anti-Sj)-associated autoimmune cerebellar ataxia, encephalitis and peripheral neuropathy: review of the literature |
| title_full_unstemmed | Inositol 1,4,5-trisphosphate receptor type 1 autoantibody (ITPR1-IgG/anti-Sj)-associated autoimmune cerebellar ataxia, encephalitis and peripheral neuropathy: review of the literature |
| title_short | Inositol 1,4,5-trisphosphate receptor type 1 autoantibody (ITPR1-IgG/anti-Sj)-associated autoimmune cerebellar ataxia, encephalitis and peripheral neuropathy: review of the literature |
| title_sort | inositol 1 4 5 trisphosphate receptor type 1 autoantibody itpr1 igg anti sj associated autoimmune cerebellar ataxia encephalitis and peripheral neuropathy review of the literature |
| topic | Anti-neuronal autoantibodies Inositol 1,4,5-trisphosphate receptor type 1 antibodies (ITPR1-IgG) Anti-Sj Autoimmune encephalitis Paraneoplastic neurological syndromes Dementia |
| url | https://doi.org/10.1186/s12974-022-02545-4 |
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