Correlation of Helicobacter pylori Antibody Serotypes,Immune Response,and Gut Microbiota in Children with Abdominal-type Henoch-Schönlein Purpura Presenting with Gastrointestinal Hemorrhage
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摘要:
目的 探究腹型过敏性紫癜(henoch-schönlein purpura,HSP)发生消化道出血患儿(helicobacter pylori,HP)抗体分型、免疫反应及肠道菌群的相关性。 方法 在2021年2月至2025年2月期间,河北省儿童医院针对96例腹型HSP发生消化道出血患儿的病例为研究对象(出血组),依1:1原则选取同期收治的HSP未发生消化道出血患儿96例(非出血组)、体检健康儿童96例(健康组)进行对照研究,比较各组HP抗体分型、免疫反应[肿瘤坏死因子-α(tumor necrosis factor-a,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-8(interleukin-6,IL-8)、T细胞表面分化抗原3阳性(cluster of differentiation 3 positive,CD3+)、T细胞表面分化抗原4阳性(Cluster of Differentiation 4 positive,CD4+)、T细胞表面分化抗原8阳性(cluster of differentiation 8 positive,CD8+)、CD4+/CD8+]及肠道菌群的差异。并比较HP抗体阳性组与阴性组在免疫反应及肠道菌群上的差异,并通过皮尔逊相关性分析探讨上述指标间的关联性。 结果 出血组HP抗体Ⅰ型发生率 > 非出血组 > 健康组,HP抗体阴性率 < 非出血组 < 健康组(P < 0.05)。出血组TNF-α、IL-6、IL-8、CD8+、大肠杆菌 > 非出血组 > 健康组,CD3+、CD4+、CD4+/CD8+、双歧杆菌、乳酸杆菌 < 非出血组 < 健康组(P < 0.05)。HSP发生消化道出血患儿HP抗体阳性组TNF-α、IL-6、IL-8、CD8+、大肠杆菌均高于HP抗体阴性组,CD3+、CD4+、CD4+/CD8+、双歧杆菌、乳酸杆菌均低于HP抗体阴性组(P < 0.05)。皮尔逊相关性显示,TNF-α、IL-6、IL-8、CD3+、CD4+、CD4+/CD8+均与大肠杆菌、乳酸杆菌、双歧杆菌存在相关(P < 0.05),CD8+与大肠杆菌呈正相关(P < 0.05)。 结论 腹型HSP发生消化道出血患儿HP抗体阳性率更高,且存在免疫反应及肠道屏障功能紊乱;HP抗体阳性患儿的免疫反应及肠道菌群紊乱程度甚于阴性患儿,且免疫反应与肠道屏障功能指标间存在显著相关性。 Abstract:Objective To investigate the correlation between Helicobacter pylori (HP) antibody subtypes, immune response, and intestinal microbiota in children with abdominal Henoch-Schönlein purpura (HSP) complicated by gastrointestinal bleeding. Methods From February 2021 to February 2025, 96 children with abdominal HSP complicated by gastrointestinal bleeding admitted to Hebei Children's Hospital were enrolled as the bleeding group. According to a 1:1 matching principle, 96 children with HSP without gastrointestinal bleeding treated during the same period (non-bleeding group) and 96 healthy children undergoing physical examination (healthy group) were selected as controls. The study compared HP antibody subtypes, immune responses [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), cluster of differentiation 3 positive (CD3+), cluster of differentiation 4 positive (CD4+), cluster of differentiation 8 positive (CD8+), CD4+/CD8+ ratio], and intestinal microbiota among the three groups. Differences in immune response and intestinal microbiota between the HP antibody-positive and HP antibody-negative groups were compared. Pearson correlation analysis was performed to explore associations among these indicators. Results The incidence of HP antibody type I in the bleeding group was greater than the non-bleeding group, which was greater than the healthy group, while the negative rate of HP antibody showed the opposite pattern (P < 0.05). In the bleeding group, TNF-α, IL-6, IL-8, CD8+, and Escherichia coli levels were higher than in the non-bleeding group, which were higher than in the healthy group. CD3+, CD4+, CD4+/CD8+ ratio, Bifidobacterium, and Lactobacillus levels were lower than in the non-bleeding group, which were lower than in the healthy group (P < 0.05). Among children with abdominal HSP complicated by gastrointestinal bleeding, the HP antibody-positive group showed higher TNF-α, IL-6, IL-8, CD8+, and Escherichia coli levels compared to the HP antibody-negative group, while CD3+, CD4+, CD4+/CD8+ ratio, Bifidobacterium, and Lactobacillus levels were lower (P < 0.05). Pearson correlation analysis revealed that TNF-α, IL-6, IL-8, CD3+, CD4+, and CD4+/CD8+ were correlated with Escherichia coli, Lactobacillus, and Bifidobacterium (P < 0.05), and CD8+ showed a positive correlation with Escherichia coli (P < 0.05). Conclusion Children with abdominal HSP complicated by gastrointestinal bleeding have a higher positive rate of HP antibodies and exhibit dysregulated immune response and compromised intestinal barrier function. HP antibody-positive children demonstrate more severe immune dysfunction and intestinal microbiota dysbiosis compared to antibody-negative children, with significant correlations between immune response parameters and intestinal barrier function markers. -
表 1 各组一般资料比较[($ \bar x \pm s $)/[n(%)]
Table 1. Comparison of General Information among Groups[($ \bar x \pm s $)/[n (%)]
组别 n 性别(男/女) 年龄(岁) 体重(kg) 病程(d) 疾病活动度(分) 治疗史 轻度 中度 重度 糖皮质激素 免疫抑制剂 健康组 96 52/44 8.05 ± 1.71 22.40 ± 2.70 − − − − 非出血组 96 50/46 8.08 ± 1.51 21.90 ± 2.90 19.58 ± 3.60 48(50) 35(36.46) 13(13.54) 55(57.29) 5(5.21) 出血组 96 53/43 8.29 ± 1.49 22.10 ± 2.50 20.19 ± 2.52 38(39.58) 40(41.67) 18(18.75) 68(70.83) 12(12.5) F/t/χ2 − 0.196 0.657 0.831 1.347 2.106 0.547 0.962 3.823 3.162 P − 0.907 0.519 0.437 0.18 0.147 0.46 0.327 0.051 0.075 表 2 各组HP抗体分型比较[n(%)]
Table 2. Comparison of HP antibody typing among different groups [n (%)]
组别 n HP感染阳性 HP感染阴性 Ⅰ型 Ⅱ型 中间型 健康组 96 2(2.08) 2(2.08) 3(3.13) 89(92.71) 非出血组 96 28(29.17)a 3(3.13) 10(10.42)a 55(57.29)a 出血组 96 49(51.04)ab 7(7.29) 5(5.21) 35(36.46)ab χ2 − 5.154 0.452 2.005 66.011 P − < 0.001* 0.651 0.081 < 0.001* 与健康组比较,aP < 0.05;与非出血组比较,bP < 0.05;*P < 0.05。 表 3 各组免疫反应及肠道菌群比较($ \bar x \pm s $)
Table 3. Comparison of immune responses and gut microbiota among different groups($ \bar x \pm s $)
指标 项目 健康组(n = 96) 非出血组(n = 96) 出血组(n = 96) F P 炎症因子 TNF-α(pg/mL) 21.49 ± 3.36 26.35 ± 4.13a 39.19 ± 10.15ab 183.328 < 0.001* IL-6(pg/mL) 17.39 ± 3.14 22.3 ± 4.33a 40.65 ± 7.65ab 497.976 < 0.001* IL-8(pg/mL) 12.28 ± 3.31 16.3 ± 3.51a 28.30 ± 8.76ab 199.958 < 0.001* 免疫功能 CD3+(%) 52.39 ± 5.14 44.31 ± 4.28a 33.88 ± 6.80ab 272.599 < 0.001* CD4+(%) 39.86 ± 3.19 36.29 ± 2.58a 31.08 ± 6.45ab 96.020 < 0.001* CD8+(%) 23.72 ± 2.36 25.59 ± 2.41a 28.34 ± 4.72ab 46.122 < 0.001* CD4+/CD8+ 1.69 ± 0.16 1.43 ± 0.12a 1.11 ± 0.22ab 275.46 < 0.001* 肠道菌群 双歧杆菌 9.93 ± 0.37 9.51 ± 0.48a 8.83 ± 0.44ab 158.121 < 0.001* 乳酸杆菌 8.07 ± 0.34 7.18 ± 0.47a 6.61 ± 0.53ab 250.646 < 0.001* 大肠杆菌 8.85 ± 0.54 9.48 ± 0.35a 10.02 ± 0.67ab 114.181 < 0.001* 与健康组比较,aP < 0.05;与非出血组比较,bP < 0.05;*P < 0.05。 表 4 HSP发生消化道出血患儿HP抗体阴性组与阳性组免疫反应及肠道菌群比较($ \bar x \pm s $)
Table 4. Comparison of immune response and gut microbiota between HP antibody negative and positive groups in children with HSP induced gastrointestinal bleeding($ \bar x \pm s $)
指标 项目 HP抗体阳性组(n = 61) HP抗体阴性组(n = 35) t P 炎症因子 TNF-α(pg/mL) 43.24 ± 8.92 32.13 ± 8.17 6.053 < 0.001* IL-6(pg/mL) 44.89 ± 5.00 33.26 ± 5.51 10.567 < 0.001* IL-8(pg/mL) 33.45 ± 5.43 19.33 ± 5.67 12.067 < 0.001* 免疫功能 CD3+(%) 31.83 ± 6.16 37.45 ± 6.45 4.229 < 0.001* CD4+(%) 29.64 ± 5.97 33.6 ± 6.56 3.017 0.003 CD8+(%) 29.08 ± 4.84 27.04 ± 4.27 2.073 0.041 CD4+/CD8+ 1.03 ± 0.18 1.25 ± 0.22 5.477 < 0.001* 肠道屏障功能 乳酸杆菌 8.61 ± 0.32 9.21 ± 0.36 8.437 < 0.001* 双歧杆菌 6.48 ± 0.53 6.85 ± 0.45 3.472 < 0.001* 大肠杆菌 10.26 ± 0.63 9.61 ± 0.54 5.11 < 0.001* *P < 0.05。 表 5 免疫反应及肠道菌群相关性分析
Table 5. Correlation analysis between immune response and gut microbiota
皮尔逊相关性 乳酸杆菌 双歧杆菌 大肠杆菌 TNF-α r −0.435 −0.431 0.789 P < 0.001* < 0.001* < 0.001* IL-6 r −0.573 −0.543 0.786 P < 0.001* < 0.001* < 0.001* IL-8 r −0.501 −0.476 0.770 P < 0.001* < 0.001* < 0.001* CD3+ r 0.831 0.862 −0.333 P < 0.001* < 0.001* < 0.001* CD4+ r 0.742 0.734 −0.193 P < 0.001* < 0.001* 0.001 CD8+ r −0.110 −0.103 0.722 P 0.063 0.08 < 0.001* CD4+/CD8+ r 0.619 0.628 −0.629 P < 0.001* < 0.001* < 0.001* n 288 288 288 *P < 0.05。 -
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