Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Pécs Medical School, Pécs, Hungary.
Institute of Mathematics and Informatics, University of Pécs, Pécs, Hungary.
Front Immunol. 2021 Jun 29;12:690940. doi: 10.3389/fimmu.2021.690940. eCollection 2021.
In children undergoing chemotherapy yearly influenza vaccination is recommended by treatment protocols. We investigated the relationship between cellular immunity and the antibody response to inactivated influenza vaccines.
25 patients (age: 2-18 years) undergoing chemotherapy for different malignancies participated in our study. Flow cytometric detection of peripheral blood lymphocyte subpopulations together with hemagglutination inhibition antibody titers were measured before and 21-28 days after vaccination. We examined the ratio and total numbers of CD3+, CD4+, CD8+ T cells, activated helper (CD3+CD4+CD25), regulatory (CD3+CD4+CD25), naive (CD3+CD45RA+) and memory (CD3+CD45RO+) T cells, CD56+NK, and CD3+CD56+ (NKT-like) cells. Relationships between specific antibody responses (seroprotection, seroconversion, geometric mean titer (GMT), geometric mean fold increase (GMFI)) and the ratios and counts of lymphocyte subpopulations were evaluated using one-way ANOVA and the paired sample t test after dichotomization according to age-related reference values.
Patients with CD4+ lymphocyte levels in the normal age-specific range showed significantly better response regarding postvaccination GMT elevation for H1N1 and H3N2 strains (97.52 . 19.2, p=0.019, 80 . 14.43, p=0.021, respectively). GMFI results were significant only against B strain (2.69-fold . 1.23-fold, p=0.046). Prevaccination CD3+CD56+ (NKT-like) cells above predicted values according to age showed significant associations both in postvaccination GMT elevation (H1N1: 75.11 . 14.14, p=0.010; H3N2: 62.18 . 11.22, p=0.012; B: 22.69 . 6.67, p=0.043) and GMFI against all three strains (H1N1: 3.76-fold . 1.06-fold, p=0.015; H3N2: 2.74-fold . 1, p=0.013; B: 2.57-fold . 1, p=0.008). By one-way ANOVA, we found a positive relation between absolute lymphocyte cell count above 1000/µl and the postvaccination GMT elevation against H3N2 (12.81 vs. 56.56, p=0.032), and GMFI regarding H1N1 (1.22-fold . 3.48-fold, p=0.044).
In addition to verifying the predictive value of absolute lymphocyte count above 1000/µl, our results suggest an association between NKT-like cell counts and the specific antibody response against all three investigated influenza strains in highly immunosuppressed patients. Furthermore, prevaccination CD4+ lymphocyte levels in the normal age-specific range may influence seroresponse.
根据治疗方案,建议在接受化疗的儿童中每年接种流感疫苗。我们研究了细胞免疫与灭活流感疫苗抗体反应之间的关系。
25 名(年龄:2-18 岁)正在接受不同恶性肿瘤化疗的患者参与了我们的研究。在接种疫苗前和 21-28 天后,通过流式细胞术检测外周血淋巴细胞亚群,并测量血凝抑制抗体滴度。我们检查了 CD3+、CD4+、CD8+T 细胞、辅助激活(CD3+CD4+CD25)、调节(CD3+CD4+CD25)、幼稚(CD3+CD45RA+)和记忆(CD3+CD45RO+)T 细胞、CD56+NK 和 CD3+CD56+(NKT 样)细胞的比例和总数。使用单向方差分析和配对样本 t 检验评估特定抗体反应(血清保护、血清转化、几何平均滴度(GMT)、几何平均倍数增加(GMFI))与淋巴细胞亚群比例和计数之间的关系,并根据年龄相关参考值进行二分类。
CD4+淋巴细胞水平在正常年龄特异性范围内的患者在接种 H1N1 和 H3N2 株疫苗后 GMT 升高方面表现出显著更好的反应(97.52. 19.2,p=0.019,80. 14.43,p=0.021)。GMFI 结果仅对 B 株具有统计学意义(2.69 倍. 1.23 倍,p=0.046)。接种疫苗前 CD3+CD56+(NKT 样)细胞高于年龄预测值与接种疫苗后 GMT 升高(H1N1:75.11. 14.14,p=0.010;H3N2:62.18. 11.22,p=0.012;B:22.69. 6.67,p=0.043)和 GMFI 对所有三种菌株均有显著相关性(H1N1:3.76 倍. 1.06 倍,p=0.015;H3N2:2.74 倍. 1,p=0.013;B:2.57 倍. 1,p=0.008)。通过单向方差分析,我们发现绝对淋巴细胞计数超过 1000/µl 与接种 H3N2 后 GMT 升高呈正相关(12.81 vs. 56.56,p=0.032),以及与 H1N1 相关的 GMFI(1.22 倍. 3.48 倍,p=0.044)。
除了验证绝对淋巴细胞计数超过 1000/µl 的预测值外,我们的结果还表明,在高度免疫抑制的患者中,NKT 样细胞计数与针对所有三种研究流感株的特定抗体反应之间存在关联。此外,接种疫苗前 CD4+淋巴细胞水平在正常年龄特异性范围内可能会影响血清反应。