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Abstract：
UNASSIGNED: Anti-IgLON5 disease is a rare chronic autoimmune disorder characterized by IgLON5 autoantibodies predominantly of the IgG4 subclass. Distinct pathogenic effects were described for anti-IgLON5 IgG1 and IgG4, however, with uncertain clinical relevance.
UNASSIGNED: IgLON5-specific IgG1-4 levels were measured in 46 sera and 20 cerebrospinal fluid (CSF) samples from 13 HLA-subtyped anti-IgLON5 disease patients (six females, seven males) using flow cytometry. Intervals between two consecutive serum or CSF samplings (31 and 10 intervals, respectively) were categorized with regard to the immunomodulatory treatment active at the end of the interval, changes of anti-IgLON5 IgG1 and IgG4 levels, and disease severity. Intrathecal anti-IgLON5 IgG4 synthesis (IS) was assessed using a quantitative method.
UNASSIGNED: The median age at onset was 66 years (range: 54-75), disease duration 10 years (range: 15-156 months), and follow-up 25 months (range: 0-83). IgLON5-specific IgG4 predominance was observed in 38 of 46 (83%) serum and 11 of 20 (55%) CSF samples. Anti-IgLON5 IgG4 levels prior clinical improvement in CSF but not serum were significantly lower than in those prior stable/progressive disease. Compared to IgLON5 IgG4 levels in serum, CSF levels in HLA-DRB1*10:01 carriers were significantly higher than in non-carriers. Indeed, IgLON5-specific IgG4 IS was demonstrated not only in four of five HLA-DRB1*10:01 carriers but also in one non-carrier. Immunotherapy was associated with decreased anti-IgGLON5 IgG serum levels. In CSF, lower anti-IgLON5 IgG was associated with immunosuppressive treatments used in combination, that is, corticosteroids and/or azathioprine plus intravenous immunoglobulins or rituximab.
UNASSIGNED: Our findings might indicate that CSF IgLON5-specific IgG4 is frequently produced intrathecally, especially in HLA-DRB1*10:01 carriers. Intrathecally produced IgG4 may be clinically relevant. While many immunotherapies reduce serum IgLON5 IgG levels, more intense immunotherapies induce clinical improvement and may be able to target intrathecally produced anti-IgLON5 IgG. Further studies need to confirm whether anti-IgLON5 IgG4 IS is a suitable prognostic and predictive biomarker in anti-IgLON5 disease.
UNASSIGNED: IgLON5-specific IgG1-4 levels were measured in 46 sera and 20 cerebrospinal fluid (CSF) samples from 13 HLA-subtyped anti-IgLON5 disease patients (six females, seven males) using flow cytometry. Intervals between two consecutive serum or CSF samplings (31 and 10 intervals, respectively) were categorized with regard to the immunomodulatory treatment active at the end of the interval, changes of anti-IgLON5 IgG1 and IgG4 levels, and disease severity. Intrathecal anti-IgLON5 IgG4 synthesis (IS) was assessed using a quantitative method.
UNASSIGNED: The median age at onset was 66 years (range: 54-75), disease duration 10 years (range: 15-156 months), and follow-up 25 months (range: 0-83). IgLON5-specific IgG4 predominance was observed in 38 of 46 (83%) serum and 11 of 20 (55%) CSF samples. Anti-IgLON5 IgG4 levels prior clinical improvement in CSF but not serum were significantly lower than in those prior stable/progressive disease. Compared to IgLON5 IgG4 levels in serum, CSF levels in HLA-DRB1*10:01 carriers were significantly higher than in non-carriers. Indeed, IgLON5-specific IgG4 IS was demonstrated not only in four of five HLA-DRB1*10:01 carriers but also in one non-carrier. Immunotherapy was associated with decreased anti-IgGLON5 IgG serum levels. In CSF, lower anti-IgLON5 IgG was associated with immunosuppressive treatments used in combination, that is, corticosteroids and/or azathioprine plus intravenous immunoglobulins or rituximab.
UNASSIGNED: Our findings might indicate that CSF IgLON5-specific IgG4 is frequently produced intrathecally, especially in HLA-DRB1*10:01 carriers. Intrathecally produced IgG4 may be clinically relevant. While many immunotherapies reduce serum IgLON5 IgG levels, more intense immunotherapies induce clinical improvement and may be able to target intrathecally produced anti-IgLON5 IgG. Further studies need to confirm whether anti-IgLON5 IgG4 IS is a suitable prognostic and predictive biomarker in anti-IgLON5 disease.
摘要：
抗IgLON5疾病是一种罕见的慢性自身免疫性疾病，其特征是IgLON5自身抗体主要为IgG4亚类。然而，抗IgLON5IgG1和IgG4描述了不同的致病作用，具有不确定的临床相关性。
■在13名HLA亚型抗IgLON5病患者的46份血清和20份脑脊液（CSF）样本中测量了IgLON5特异性IgG1-4水平（六名女性，七个雄性)使用流式细胞术。两次连续血清或CSF采样之间的间隔（31和10间隔，分别)根据间隔结束时的免疫调节治疗活性进行分类，抗IgLON5IgG1和IgG4水平的变化，和疾病的严重程度。使用定量方法评估鞘内注射抗IgLON5IgG4合成(IS)。
■发病年龄中位数为66岁（范围：54-75），病程10年（范围：15-156个月），随访25个月（范围：0-83）。在46份(83%)血清中的38份和20份(55%)CSF样品中的11份中观察到IgLON5特异性IgG4占优势。在CSF而非血清中的临床改善之前的抗IgLON5IgG4水平显著低于在先前的稳定/进行性疾病中的那些。与血清中IgLON5IgG4水平相比，HLA-DRB1*10:01携带者的CSF水平明显高于非携带者。的确,IgLON5特异性IgG4IS不仅在五个HLA-DRB1*10:01携带者中的四个中得到证实，而且在一个非携带者中也得到证实。免疫治疗与抗IgGLON5IgG血清水平降低相关。在CSF中，较低的抗IgLON5IgG与联合使用的免疫抑制治疗相关，也就是说,皮质类固醇和/或硫唑嘌呤加静脉注射免疫球蛋白或利妥昔单抗。
■我们的发现可能表明脑脊液IgLON5特异性IgG4经常在鞘内产生，尤其是HLA-DRB1*10:01携带者。鞘内产生的IgG4可能是临床相关的。虽然许多免疫疗法降低血清IgLON5IgG水平，更强烈的免疫疗法诱导临床改善,并且可能能够靶向鞘内产生的抗IgLON5IgG.进一步的研究需要确认抗IgLON5IgG4IS是否是抗IgLON5疾病中合适的预后和预测性生物标志物。
■在13名HLA亚型抗IgLON5病患者的46份血清和20份脑脊液（CSF）样本中测量了IgLON5特异性IgG1-4水平（六名女性，七个雄性)使用流式细胞术。两次连续血清或CSF采样之间的间隔（31和10间隔，分别)根据间隔结束时的免疫调节治疗活性进行分类，抗IgLON5IgG1和IgG4水平的变化，和疾病的严重程度。使用定量方法评估鞘内注射抗IgLON5IgG4合成(IS)。
■发病年龄中位数为66岁（范围：54-75），病程10年（范围：15-156个月），随访25个月（范围：0-83）。在46份(83%)血清中的38份和20份(55%)CSF样品中的11份中观察到IgLON5特异性IgG4占优势。在CSF而非血清中的临床改善之前的抗IgLON5IgG4水平显著低于在先前的稳定/进行性疾病中的那些。与血清中IgLON5IgG4水平相比，HLA-DRB1*10:01携带者的CSF水平明显高于非携带者。的确,IgLON5特异性IgG4IS不仅在五个HLA-DRB1*10:01携带者中的四个中得到证实，而且在一个非携带者中也得到证实。免疫治疗与抗IgGLON5IgG血清水平降低相关。在CSF中，较低的抗IgLON5IgG与联合使用的免疫抑制治疗相关，也就是说,皮质类固醇和/或硫唑嘌呤加静脉注射免疫球蛋白或利妥昔单抗。
■我们的发现可能表明脑脊液IgLON5特异性IgG4经常在鞘内产生，尤其是HLA-DRB1*10:01携带者。鞘内产生的IgG4可能是临床相关的。虽然许多免疫疗法降低血清IgLON5IgG水平，更强烈的免疫疗法诱导临床改善,并且可能能够靶向鞘内产生的抗IgLON5IgG.进一步的研究需要确认抗IgLON5IgG4IS是否是抗IgLON5疾病中合适的预后和预测性生物标志物。
