Evaluation of Immune and Vaccine Competence in Steroid-Sensitive Nephrotic Syndrome Pediatric Patients.
Evaluation of Immune and Vaccine Competence in Steroid-Sensitive Nephrotic Syndrome Pediatric Patients.
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DOI：
10.3389/fimmu.2021.602826
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发表时间：
2021
影响因子：
7.3
通讯作者：
Vivarelli M
中科院分区：
文献类型：
--
作者：
Colucci M;Piano Mortari E;Zotta F;Corrente F;Concato C;Carsetti R;Emma F;Vivarelli M
特发性肾病综合征是一种儿童肾脏疾病，其特征是肾小球滤过屏障受损，导致蛋白质大量渗漏到尿液中。这种严重的蛋白尿引起短暂但强烈的血清IgG降低。因此，在肾病综合征中，特别是在疾病的活动性阶段，通过测量血清保护性抗体水平来评估疫苗的能力可能会产生误导。为了克服这一问题，在测定血清抗原特异性IgG的同时，我们用ELISPOT定量测定了11例类固醇敏感性肾病综合征（SSNS）患儿在接受任何免疫抑制治疗前发病时，由破伤风和乙型肝炎病毒（HBV）免疫诱导的抗原特异性记忆B细胞的数量（平均年龄5.1±0.9岁）。5名年龄匹配的非免疫介导性肾-泌尿系统疾病儿童作为对照组（平均年龄6.9±2.3岁）。所有SSNS患者血清总IgG水平均低于520 mg/dl。与此同时，与对照组相比，抗破伤风和抗hbv IgG的中位水平显著降低[分别为0.05 (0.03-0.16)vs 0.45 (0.29-3.10) IU/ml和0.0 (0.0 - 0.5)vs 30.3 (5.5-400.8) mIU/ml；两者的p = 0.02]，血清IgG滴度低于保护阈值，7/11 SSNS患者为破伤风，9/11 SSNS患者为HBV。相比之下，所有SSNS患者都有B细胞反应，显示总分泌igg的B细胞数量为100 000个计数/106个刺激细胞。抗破伤风和抗hbv IgG分泌B细胞的数量也与对照组相当（p = 0.24, p = 0.32），记忆性抗破伤风和抗hbv IgG分泌B细胞的频率占IgG分泌B细胞总数的0.1%。综上所述，SSNS患儿在发病前免疫抑制治疗中表现出对破伤风和HBV的免疫和疫苗应答，这可以通过抗原特异性记忆B细胞的定量而不是通过测定血清IgG水平来正确评估。这种方法可以早期识别免疫和疫苗能力的损害，这可能是由于在疾病过程中长期使用不同的免疫抑制药物造成的。
Idiopathic nephrotic syndrome is a childhood renal disease characterized by a damage of the glomerular filtration barrier leading to an intense leakage of proteins into the urine. This severe proteinuria causes a transient but strong reduction of serum IgG. Therefore, evaluation of vaccine competence by measuring serum levels of protective antibodies can be misleading in nephrotic syndrome, especially during the active phase of disease. To overcome this issue, in parallel to measuring serum antigen-specific IgG, we quantified by ELISPOT the number of antigen-specific memory B cells induced by previous immunization with tetanus and hepatitis B virus (HBV) in 11 steroid-sensitive nephrotic syndrome (SSNS) pediatric patients at onset before any immunosuppressive treatment (mean age 5.1±0.9 years). Five age-matched children with non-immunomediated nephro-urologic disorders were also enrolled as controls (mean age 6.9±2.3 years). Low total serum IgG levels (<520 mg/dl) were found in all the analyzed SSNS patients. In parallel, median levels of anti-tetanus and anti-HBV IgG were significantly reduced compared to controls [0.05 (0.03–0.16) vs. 0.45 (0.29–3.10) IU/ml and 0.0 (0.0–0.5) vs. 30.3 (5.5–400.8) mIU/ml, respectively; p = 0.02 for both], with serum IgG titers below protective threshold in 7/11 SSNS patients for tetanus and in 9/11 SSNS patients for HBV. In contrast, all SSNS patients had a competent B-cell response, showing an amount of total IgG-secreting B cells >1,000 counts/106 stimulated cells. The amount of anti-tetanus and anti-HBV IgG-secreting B cells was also comparable to that of controls (p = 0.24, p = 0.32, respectively), with a frequency of memory anti-tetanus and anti-HBV IgG secreting B cells >0.1% of total IgG secreting B cells. In conclusion, SSNS children at disease onset pre-immunosuppressive therapy showed a competent immune and vaccine response against tetanus and HBV, which can be correctly evaluated by quantification of antigen-specific memory B cells rather than by measuring serum IgG levels. This approach allows early identification of the impairment of immune and vaccine competence, which may derive from protracted use of different immunosuppressive drugs during disease course.
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影响因子：
3
作者：
LAMANNA, A;POLITO, C;DELGADO, R
通讯作者：
DELGADO, R
影响因子：
3
作者：
Colucci, Manuela;Carsetti, Rita;Vivarelli, Marina
通讯作者：
Vivarelli, Marina
影响因子：
158.5
作者：
GIANGIACOMO, J;CLEARY, TG;ROBSON, AM
通讯作者：
ROBSON, AM
影响因子：
3.4
作者：
Bonanni, Alice;Calatroni, Marta;Ghiggeri, Gian Marco
通讯作者：
Ghiggeri, Gian Marco
影响因子：
5.5
作者：
Yildiz, N.;Sever, Lale;Caliskan, S.
通讯作者：
Caliskan, S.