Relationship of Serum IL-27，CysC，GAPDH Antibodies with Disease Severity and Prognosis in Children with Neuromyelitis Optica Spectrum Disorder
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摘要:
目的 探讨血清白细胞介素-27（interleukin-27，IL-27）、胱抑素C（cystatin C，CysC）、3-磷酸甘油醛脱氢酶（glyceraldehyde-3-phosphate dehydrogenase，GAPDH）抗体与视神经脊髓炎谱系疾病（neuromyelitis optica spectrum disorder，NMOSD）患儿病情程度的关系及对预后的影响。 方法 选取2019年7月至2023年7月昆明市儿童医院收治的102例NMOSD患儿，另选取同期健康儿童102名，比较NMOSD患儿与健康儿童血清IL-27、CysC、GAPDH抗体水平，对比不同病情NMOSD患儿血清IL-27、CysC、GAPDH抗体水平，分析血清IL-27、CysC、GAPDH抗体与病情、脑脊液标志物的相关性。针对102例NMOSD患儿给予个体化治疗，随访1年，以是否发生疾病复发评估预后，分为复发组与未复发组，比较两组临床资料、血清IL-27、CysC、GAPDH抗体水平，分析血清IL-27、CysC、GAPDH抗体对疾病复发的影响，评价血清IL-27、CysC、GAPDH抗体对疾病复发的预测价值。 结果 NMOSD患儿血清IL-27、CysC水平低于健康儿童，GAPDH抗体水平高于健康儿童（P < 0.05）；血清IL-27、CysC与水通道蛋白4（Aquaporin 4，AQP4）-IgG抗体阳性、脊髓受累节段数、扩展残疾状态量表（Expanded disability status scale，EDSS）评分、脑脊液蛋白含量、白细胞数呈负相关，GAPDH抗体与AQP4-IgG抗体阳性、脊髓受累节段数、EDSS评分、脑脊液蛋白含量、白细胞数呈正相关（P < 0.05）；随访1年，失访2例，疾病复发21例，疾病未复发79例，分别纳入复发组与未复发组。复发组与未复发组脊髓受累节段数、EDSS评分、脑脊液蛋白含量比较，差异有统计学意义（P < 0.05）；复发组血清IL-27、CysC水平低于未复发组，GAPDH抗体水平高于未复发组（P < 0.05）；血清IL-27、CysC、GAPDH抗体与疾病复发显著相关（P < 0.05）；血清IL-27、CysC、GAPDH抗体预测NMOSD患儿疾病复发的曲线下面积（Area under the curve，AUC）为0.748、0.791、0.747，最佳截断值分别为38.77 pg/mL、0.79 mg/L、55.81 pg/mL；三者联合预测NMOSD患儿疾病复发的AUC为0.900，优于单独预测价值（Z = 2.215、2.137、2.220，P = 0.024、0.033、0.023）。 结论 血清IL-27、CysC、GAPDH抗体与NMOSD患儿病情程度和预后显著相关，可有效预测疾病复发风险，且联合检测时能取得更可靠的预测价值。 -
关键词:
- 视神经脊髓炎谱系疾病 /
- 白细胞介素-27 /
- 胱抑素C /
- 3-磷酸甘油醛脱氢酶抗体 /
- 病情程度 /
- 预后 /
- 相关性
Abstract:Objective To explore the relationship between serum Interleukin-27 （IL-27）, Cystatin C （CysC）, and Glyceraldehyde-3-phosphate dehydrogenase （GAPDH） antibodies and the severity of disease in children with Neuromyelitis optica spectrum disorder （NMOSD）, as well as their impact on prognosis. Methods A total of 102 children with NMOSD admitted to Kunming Children's Hospital from July 2019 to July 2023 were selected, along with 102 healthy during the same period. Serum levels of IL-27, CysC, and GAPDH antibodies were compared between children with NMOSD and healthy children. The levels of serum IL-27, CysC, and GAPDH antibodies were compared among children with varying disease severity. The correlations between serum IL-27, CysC, GAPDH antibodies and disease condition, cerebrospinal fluid markers were analyzed. And 102 children with NMOSD received individualized treatment and were followed up for 1 year. The prognosis was evaluated based on disease relapse, and patients were divided into recurrence group and non-recurrence group. The clinical data, serum IL-27, CysC, and GAPDH antibody levels were compared between the two groups. the impact of serum IL-27, CysC, and GAPDH antibodies on disease recurrence was analyzed, and the predictive value of serum IL-27, CysC, and GAPDH antibodies for disease recurrence was evaluated. Results Children with NMOSD had lower levels of serum IL-27 and CysC and higher levels of GAPDH antibodies than healthy children （P < 0.05）. Serum IL-27 and CysC levels were negatively correlated with Aquaporin 4 （AQP4）-IgG antibody positivity, the number of spinal cord-involved segments, Expanded disability status scale （EDSS） scores, cerebrospinal fluid protein content, and white blood cell count. In contrast GAPDH antibodies were positively correlated with these parameters （P < 0.05）. After 1-year follow-up, 2 cases were lost to follow-up, 21 cases relapsed, and 79 cases did not, which were included in the relapse group and non-relapse group, respectively. There were significant differences in the number of spinal cord-involved segments, EDSS scores, and cerebrospinal fluid protein content between the relapse group and non-relapse group （P < 0.05）. The levels of serum IL-27 and CysC were lower and the levels of GAPDH antibodies were higher in the relapse group than the non-relapse group （P < 0.05）. Serum IL-27, CysC, and GAPDH antibodies were significantly associated with disease relapse （P < 0.05）. The Area under the curve （AUC） values for predicting disease recurrence in children with NMOSD based on serum IL-27, CysC, and GAPDH antibodies were 0.748, 0.791, and 0.747, respectively, with optimal cutoff values of 38.77 pg/mL, 0.79 mg/L, and 55.81 pg/mL, respectively. The combined prediction of disease relapse using these three markers had an AUC of 0.900, which was superior to individual prediction values （Z = 2.215, 2.137, 2.220, P = 0.024, 0.033, 0.023）. Conclusion The levels of serum IL-27, CysC, and GAPDH antibodies are significantly correlated with the disease severity and prognosis in children with NMOSD, and can effectively predict the risk of disease recurrence. Combined detection provides more reliable predictive value. -
图 1 血清IL-27、CysC、GAPDH抗体对疾病复发的预测价值
Figure 1. Predictive value of serum IL-27，CysC，and GAPDH antibodies for disease recurrence
表 1 NMOSD患儿与健康儿童血清IL-27、CysC、GAPDH抗体水平比较（$ \bar x \pm s $）
Table 1. Comparison of serum IL-27，CysC，and GAPDH antibody levels between NMOSD patients and healthy children （$ \bar x \pm s $）
组别 n IL-27（pg/mL） CysC（mg/L） GAPDH抗体（pg/mL） NMOSD组 102 40.75 ± 8.34 0.82 ± 0.11 52.69 ± 10.06 健康组 102 67.29 ± 10.11 0.96 ± 0.15 45.13 ± 3.58 t 20.452 7.601 7.150 P <0.001* <0.001* <0.001* *P < 0.05。 
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表 2 不同病情NMOSD患儿血清IL-27、CysC、GAPDH抗体水平比较（$ \bar x \pm s$）
Table 2. Comparison of serum IL-27，CysC，and GAPDH antibody levels among children with different conditions of NMOSD（$ \bar x \pm s $）
组别 n IL-27（pg/mL） CysC（mg/L） GAPDH抗体（pg/mL） 疾病类型 AQP4-IgG抗体（+） 83 41.73 ± 6.18 0.82 ± 0.08 53.58 ± 5.39 MOG-IgG抗体（+） 19 36.47 ± 5.07 0.91 ± 0.11 48.80 ± 4.17 t 3.450 4.107 3.620 P <0.001* <0.001* <0.001* 脊髓受累节段数（节） ≥6 52 38.13 ± 6.37 0.75 ± 0.07 56.74 ± 6.18 <6 50 43.47 ± 5.22 0.89 ± 0.09 48.48 ± 4.02 t 4.621 8.789 7.967 P <0.001* <0.001* <0.001* EDSS评分（分） ≥4 47 37.67 ± 6.49 0.78 ± 0.08 56.31 ± 6.65 <4 55 43.38 ± 5.53 0.85 ± 0.10 49.60 ± 4.33 t 4.798 3.858 6.120 P <0.001* <0.001* <0.001* *P < 0.05。
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表 3 复发组与未复发组患儿临床资料、血清IL-27、CysC、GAPDH抗体水平比较[n（%）/（$ \bar x \pm s $）]
Table 3. Comparison of clinical data，serum IL-27，CysC，and GAPDH antibody levels between recurrence and non-recurrence groups of children[n（%）/（$ \bar x \pm s $）]
项目 复发组（n=21） 未复发组（n=79） t/χ2 P 年龄（岁） 9.16 ± 1.58 9.09 ± 1.44 0.194 0.847 性别 0.009 0.925 男 3（14.29） 13（16.46） 女 18（85.71） 66（83.54） 近期感染史 0.022 0.882 有 3（14.29） 8（10.13） 无 18（14.29） 71（89.87） 疫苗接种史 0.107 0.743 有 2（9.52） 8（10.13） 无 19（90.48） 71（89.87） 疾病类型 0.002 0.964 AQP4-IgG抗体阳性 17（80.95） 66（83.54） MOG-IgG抗体阳性 4（19.05） 13（16.46） 脊髓受累节段数（节） 6.232 0.013* ≥6 16（76.19） 36（45.57） <6 5（23.81） 43（54.43） EDSS评分（分） 6.920 0.009* ≥4 15（71.43） 31（39.24） <4 6（28.57） 48（60.76） 脑脊液蛋白含量 5.734 0.017* 增高 10（47.62） 17（21.52） 正常 11（52.38） 62（78.48） 脑脊液白细胞数 4.584 0.032* 增高 9（42.86） 14（17.72） 正常 12（57.14） 65（82.28） 血清指标 IL-27（pg/mL） 35.21 ± 8.02 42.21 ± 6.11 4.356 <0.001* CysC（mg/L） 0.72 ± 0.07 0.84 ± 0.10 5.164 <0.001* GAPDH抗体（pg/mL） 60.12 ± 10.58 50.65 ± 8.24 4.399 <0.001* *P < 0.05。
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表 4 血清IL-27、CysC、GAPDH抗体与病情、脑脊液标志物的相关性
Table 4. Correlation between serum IL-27，CysC，GAPDH antibodies and disease condition，cerebrospinal fluid markers
指标 IL-27 CysC GAPDH抗体 r P r P r P AQP4-IgG抗体阳性 −0.670 <0.001* −0.684 <0.001* 0.703 <0.001* 脊髓受累节段数 −0.619 <0.001* −0.625 <0.001* 0.664 <0.001* EDSS评分 −0.631 <0.001* −0.657 <0.001* 0.603 <0.001* 脑脊液蛋白含量 −0.617 <0.001* −0.641 <0.001* 0.655 <0.001* 脑脊液白细胞数 −0.611 <0.001* −0.634 <0.001* 0.640 <0.001* *P < 0.05。
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表 5 疾病复发的影响因素
Table 5. Factors influencing disease recurrence
变量 β SE Waldχ2 P OR 95%CI 模型1 脊髓受累节段数（以<6节为参照） 1.545 0.410 14.199 <0.001* 4.688 1.825～12.041 EDSS评分（以<4分为参照） 1.673 0.442 14.333 <0.001* 5.330 2.007～14.155 脑脊液蛋白含量（以正常为参照） 1.500 0.375 16.002 <0.001* 4.482 1.743～11.526 脑脊液白细胞数（以正常为参照） 1.344 0.406 10.958 <0.001* 3.834 1.527～9.628 IL-27 −0.341 0.068 25.115 <0.001* 0.711 0.528～0.958 CysC −0.233 0.061 14.553 <0.001* 0.792 0.652～0.963 GAPDH抗体 0.612 0.160 14.649 <0.001* 1.845 1.302～2.614 常量 −0.524 0.118 15.022 <0.001* − − 模型2 IL-27 −0.320 0.075 18.171 <0.001* 0.726 0.571～0.924 CysC −0.282 0.077 13.387 <0.001* 0.754 0.603～0.944 GAPDH抗体 0.523 0.151 11.976 <0.001* 1.686 1.206～2.358 常量 0.274 0.068 15.331 <0.001* − − *P < 0.05。
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表 6 血清IL-27、CysC、GAPDH抗体对疾病复发的预测价值
Table 6. Predictive value of serum IL-27，CysC，and GAPDH antibodies for disease recurrence
指标 AUC 截断值 敏感度（%） 特异度（%） IL-27 0.748 38.77 61.90 82.28 CysC 0.791 0.79 80.95 73.42 GAPDH抗体 0.747 55.81 66.67 81.01 联合 0.900 − 85.71 86.08
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