Tiselius Eva, Sundberg Emil, Ramilo Amor Amanda, Andersson Hanna, Varnaite Renate, Kolstad Linda, Akaberi Dario, Ling Jiaxin, Harila Arja, Saghafian-Hedengren Shanie, Hoffman Tove, Nilsson Anna
Department of Women's and Children's Health, Division of Pediatric Oncology and Pediatric Surgery, Karolinska Institutet, Stockholm, Sweden.
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
Front Immunol. 2025 Jul 2;16:1613778. doi: 10.3389/fimmu.2025.1613778. eCollection 2025.
Our understanding of protective immunity after natural viral infections in children with cancer and hematological diseases is restricted. Current cancer treatments cause significant immunosuppression, affecting both innate and adaptive immunity which leads to reduced B-cell and antibody responses. The aim of this study was to characterize SARS-CoV-2 immune response in children with cancer or hematological disease.
A single-center study was conducted from June 2020 to June 2023, including 135 patients and 14 healthy siblings. Blood samples were obtained for serological analysis and cell-based assays. SARS-CoV-2 IgG and IgA responses were quantified using suspension multiplex immunoassay (SMIA) and enzyme-linked immunosorbent assay (IgG ELISA) while neutralizing antibody (nAb) responses were assessed by plaque reduction neutralization tests (PRNT). The memory B-cell (MBC) population was evaluated through flow cytometry and MBC responses through FluoroSpot, respectively.
In total, 78 patients seroconverted in response to SARS-Co-V-2 but neither immunosuppression nor cancer diagnosis significantly affected seroconversion. SARS-CoV-2 IgG and IgA levels correlated positively with increasing age, and IgA seroconversion was significantly associated with the presence of nAbs. Antigen-specific MBC responses against both spike and receptor-binding domain (RBD) were elevated in older children, while children on immunosuppression had significantly lower RBD IgG-secreting cells.
Our results show that most pediatric oncological and hematological patients can mount a broad antibody response upon SARS-CoV-2 natural infection or vaccination, although there is a variability in their responses influenced by increasing age. MBC responses in children with immunosuppression were blunted with fewer RBD IgG-secreting cells. Essentially, our findings underscore that young children with severe treatment-related immunosuppression are at risk for less effective B-cell responses upon viral infection.
我们对癌症和血液系统疾病患儿自然病毒感染后的保护性免疫的了解有限。目前的癌症治疗会导致显著的免疫抑制，影响先天性和适应性免疫，从而导致B细胞和抗体反应降低。本研究的目的是描述癌症或血液系统疾病患儿对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的免疫反应。
2020年6月至2023年6月进行了一项单中心研究，包括135例患者和14名健康同胞。采集血样进行血清学分析和基于细胞的检测。使用悬浮多重免疫测定（SMIA）和酶联免疫吸附测定（IgG ELISA）对SARS-CoV-2 IgG和IgA反应进行定量，同时通过蚀斑减少中和试验（PRNT）评估中和抗体（nAb）反应。分别通过流式细胞术评估记忆B细胞（MBC）群体，并通过FluoroSpot评估MBC反应。
共有78例患者对SARS-CoV-2发生血清转化，但免疫抑制和癌症诊断均未显著影响血清转化。SARS-CoV-2 IgG和IgA水平与年龄增长呈正相关，IgA血清转化与nAb的存在显著相关。年龄较大的儿童针对刺突蛋白和受体结合域（RBD）的抗原特异性MBC反应升高，而接受免疫抑制治疗的儿童RBD IgG分泌细胞显著减少。
我们的结果表明，大多数儿科肿瘤和血液系统疾病患者在SARS-CoV-2自然感染或接种疫苗后能够产生广泛的抗体反应，尽管他们的反应存在差异，且受年龄增长影响。免疫抑制患儿的MBC反应减弱，RBD IgG分泌细胞较少。从本质上讲，我们的研究结果强调，患有严重治疗相关免疫抑制的幼儿在病毒感染后发生B细胞反应低效的风险较高。
