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.
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.
摘要：
背景：2014年，我们首次在该杂志中描述了自身免疫性小脑共济失调（ACA）患者中针对1,4,5-三磷酸肌醇受体1型（ITPR1-IgG/anti-Sj）的新型自身抗体。这里,我们提供了有关ITPR1-IgG/抗Sj的现有文献的综述，涵盖临床和副临床表现，肿瘤关联，血清学发现,和免疫发病机制。
方法：回顾同行评审和PubMed列出的关于ITPR1-IgG/抗Sj的英文文献。此外,我们提供了一例ITPR1-IgG相关脑炎伴认知功能减退和精神病的新患者的说明性报告.
结果：到目前为止，已鉴定出至少31例血清ITPR1-IgG/抗Sj患者(可获得21例临床信息).最常见的表现是ACA,脑病伴癫痫,脊髓病,和（神经根）神经病，包括自主神经病变.在45%的案例中，一个潜在的肿瘤存在，使这种情况成为兼性副肿瘤性神经系统疾病。除一例外，神经综合征均先于肿瘤诊断。在大多数情况下,免疫治疗仅有中度或无效果.ITPR1-IgG/抗Sj与ACA以外的表现的关联得到了一个48岁女性高滴度ITPR1-IgG/抗Sj抗体和快速认知下降的病例的证实。影响记忆，注意力和执行功能，和精神病表现，包括幻觉,在这里详细调查。FDG-PET显示右颞叶葡萄糖高代谢与边缘叶脑炎相容。有趣的是,ITPR1-IgG/抗Sj主要属于IgG2亚类在血清和脑脊液（CSF）在这个和进一步的患者，而其他患者主要是IgG1，包括那些结果更严重的人，并且在整个疾病过程中都能被检测到。静脉注射甲基强的松龙的免疫治疗，血浆置换,和静脉注射免疫球蛋白，反复进行部分或完全恢复。环磷酰胺的长期治疗与相对稳定平行，尽管患者在每个治疗周期结束时都注意到临床恶化。
结论：与ITPR1自身免疫相关的神经系统表现比最初认为的要广泛。在某些情况下，免疫疗法可能是有效的。评估ITPR1-IgG/抗Sj在认知减退和/或病因不明的精神病患者中的频率的研究是必要的。在患有ITPR1-IgG/抗Sj的患者中，肿瘤筛查是必不可少的。
方法：回顾同行评审和PubMed列出的关于ITPR1-IgG/抗Sj的英文文献。此外,我们提供了一例ITPR1-IgG相关脑炎伴认知功能减退和精神病的新患者的说明性报告.
结果：到目前为止，已鉴定出至少31例血清ITPR1-IgG/抗Sj患者(可获得21例临床信息).最常见的表现是ACA,脑病伴癫痫,脊髓病,和（神经根）神经病，包括自主神经病变.在45%的案例中，一个潜在的肿瘤存在，使这种情况成为兼性副肿瘤性神经系统疾病。除一例外，神经综合征均先于肿瘤诊断。在大多数情况下,免疫治疗仅有中度或无效果.ITPR1-IgG/抗Sj与ACA以外的表现的关联得到了一个48岁女性高滴度ITPR1-IgG/抗Sj抗体和快速认知下降的病例的证实。影响记忆，注意力和执行功能，和精神病表现，包括幻觉,在这里详细调查。FDG-PET显示右颞叶葡萄糖高代谢与边缘叶脑炎相容。有趣的是,ITPR1-IgG/抗Sj主要属于IgG2亚类在血清和脑脊液（CSF）在这个和进一步的患者，而其他患者主要是IgG1，包括那些结果更严重的人，并且在整个疾病过程中都能被检测到。静脉注射甲基强的松龙的免疫治疗，血浆置换,和静脉注射免疫球蛋白，反复进行部分或完全恢复。环磷酰胺的长期治疗与相对稳定平行，尽管患者在每个治疗周期结束时都注意到临床恶化。
结论：与ITPR1自身免疫相关的神经系统表现比最初认为的要广泛。在某些情况下，免疫疗法可能是有效的。评估ITPR1-IgG/抗Sj在认知减退和/或病因不明的精神病患者中的频率的研究是必要的。在患有ITPR1-IgG/抗Sj的患者中，肿瘤筛查是必不可少的。
