IgA血管炎儿童外周血淋巴细胞精细分群与血清免疫球蛋白的特点及机制探讨

Characteristics and Mechanism Exploration of Peripheral Blood Lymphocyte Fine Subgroupings and Serum Immunoglobulins in Children with Immunoglobulin A Vasculitis

摘要: 目的：观察IgA血管炎(IgAV)急性期患儿外周血淋巴细胞精细分群与血清免疫球蛋白的变化，以及两者之间的相关性，以探究淋巴细胞精细分群在儿童IgAV发病机制中的作用。方法：选取2021年7月至2024年1月于青岛大学附属医院确诊并于儿童肾脏风湿免疫科住院治疗的50例IgAV急性期患儿为实验组；选取同期于青岛大学附属医院健康体检的儿童27例为健康对照组。收集临床资料，应用流式细胞术检测外周血淋巴细胞精细分群，并与血清免疫球蛋白水平进行相关性分析。结果：与健康对照组比较，实验组外周血活化CD4⁺ T细胞、活化CD8⁺ T细胞、CD4⁺效应记忆T细胞、CD8⁺效应记忆T细胞、记忆调节性T细胞、双阴性T细胞、B细胞百分比升高，差异具有统计学意义(P < 0.05)；CD4⁺初始T细胞、CD8⁺初始T细胞、初始调节性T细胞、幼稚未成熟B细胞(过渡型B细胞)百分比降低，差异具有统计学意义(P < 0.05)；CD4⁺效应T细胞、CD8⁺效应T细胞、CD4⁺中央记忆T细胞、CD8⁺中央记忆T细胞、调节性T细胞、初始B细胞、经典转变型B细胞、浆母细胞、边缘区B细胞百分比差异无统计学意义(P > 0.05)。实验组血清IgA、IgE水平较健康对照组升高，差异具有统计学意义(P < 0.05)，血清IgG、IgM水平较健康对照组差异无统计学意义(P > 0.05)。实验组外周血双阴性T细胞、活化CD4⁺ T细胞、活化CD8⁺ T细胞、CD4⁺效应记忆T细胞、CD8⁺效应记忆T细胞百分比与血清IgA水平呈正相关(P < 0.05)；幼稚未成熟B细胞(过渡型B细胞)百分比与血清IgA水平呈负相关(P < 0.05)。实验组外周血活化CD4⁺ T细胞、CD4⁺效应记忆T细胞百分比与血清IgG水平呈正相关(P < 0.05)；CD4⁺初始T细胞百分比与血清IgG水平呈负相关(P < 0.05)。实验组外周血活化CD4⁺ T细胞、CD4⁺效应记忆T细胞、浆母细胞百分比与血清IgE水平呈正相关(P < 0.05)；CD4⁺初始T细胞、CD8⁺初始T细胞百分比与血清IgE水平呈负相关(P < 0.01)。实验组外周血淋巴细胞精细分群与血清IgM水平无明显相关性(P > 0.05)。结论：IgAV急性期患儿外周血淋巴细胞精细分群呈现明显失衡，主要表现为双阴性T细胞、活化T细胞、效应记忆T细胞及B细胞百分比升高，而且双阴性T细胞、活化T细胞、效应记忆T细胞百分比与血清IgA水平呈明显正相关性，提示这些淋巴细胞精细分群可能促进IgA水平升高而参与IgAV发病。

Abstract: Objective: To observe the alterations and correlations of peripheral blood lymphocyte fine subgroupings and serum immunoglobulins in children with acute-phase immunoglobulin A vasculitis (IgAV), as well as the correlations between them, and to explore the role of lymphocyte fine subgroupings in the pathogenesis of IgAV in children. Methods: Fifty children diagnosed with acute-phase IgAV and hospitalized in the Department of Pediatric Nephrology and Rheumatology Immunology at the Affiliated Hospital of Qingdao University from July 2021 to January 2024 were enrolled as the experimental group. Twenty-seven healthy children undergoing routine physical examinations during the same period were selected as the healthy control group. Clinical data were collected, and peripheral blood lymphocyte fine subgroupings were analyzed by using flow cytometry-based detection, and correlation analysis with serum immunoglobulin levels. Results: Compared with the healthy control group, the experimental group showed significantly increased percentages of peripheral blood double-negative T cells, activated CD4⁺ T cells, activated CD8⁺ T cells, CD4⁺ effector memory T cells, CD8⁺ effector memory T cells, memory regulatory T cells and B cells (P < 0.05), while the percentages of peripheral blood CD4⁺ naïve T cells, CD8⁺ naïve T cells, naïve regulatory T cells and transitional B cells were significantly decreased (P < 0.05). No statistically significant differences were observed in the percentages of peripheral blood CD4⁺ effector T cells, CD8⁺ effector T cells, CD4⁺ central memory T cells, CD8⁺ central memory T cells, regulatory T cells, naïve B cells, class-switched B cells, plasmablasts or marginal zone B cells between the experimental group and the healthy control group (P > 0.05). Serum IgA and IgE levels in the experimental group were significantly higher than those in the healthy control group (P < 0.05), while serum IgG and IgM levels showed no significant differences (P > 0.05). In the experimental group, the percentages of peripheral blood double-negative T cells, activated CD4⁺ T cells, activated CD8⁺ T cells, CD4⁺ effector memory T cells, and CD8⁺ effector memory T cells were significantly positively correlated with serum IgA levels (P < 0.05), whereas the percentages of transitional B cells was significantly negatively correlated with serum IgA levels (P < 0.05); the percentages of peripheral blood activated CD4⁺ T cells and CD4⁺ effector memory T cells were positively correlated with serum IgG levels (P < 0.05), while the percentage of CD4⁺ naïve T cells was negatively correlated with serum IgG levels (P < 0.05); the percentages of peripheral blood activated CD4⁺ T cells, CD4⁺ effector memory T cells, and plasmablasts were positively correlated with serum IgE levels (P < 0.05), while CD4⁺ naïve T cells and CD8⁺ naïve T cells showed significant negative correlations with serum IgE levels (P < 0.01). No significant correlations were observed between peripheral blood fine subgrouping of lymphocytes and serum IgM levels in the experimental group. Conclusion: In children with acute-phase IgAV, the peripheral blood lymphocyte fine subgroupings exhibited significant dysregulation, primarily characterized by increased percentages of double-negative T cells (DNT), activated T cells, effector memory T cells (Tem), and B cells. Furthermore, the proportions of DNT, activated T cells, and Tem showed a marked positive correlation with serum IgA levels, indicating that these lymphocyte fine subgroupings may promote elevated IgA production and contribute to the pathogenesis of IgAV.