Allen E Kaitlynn, Penkert Rhiannon R, Hankins Jane S, Surman Sherri L, Van de Velde Lee-Ann, Cotton Alyssa, Hayden Randall T, Tang Li, Yuan Xiaomeng, Zheng Ying, Thomas Paul G, Hurwitz Julia L
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Vaccines (Basel). 2024 Aug 29;12(9):984. doi: 10.3390/vaccines12090984.
Parvovirus B19 frequently infects children and targets cells of the erythroid lineage. Although healthy children rarely suffer severe disease, children with sickle cell disease (SCD) can experience transient red cell aplasia (TRCA), hospitalization, and life-threatening anemia upon first virus exposure. Given that children with SCD can also suffer chronic inflammation and that parvovirus B19 has been associated with autoimmune disease in other patient populations, we asked if parvovirus B19 infections contributed to acute and chronic immune abnormalities in children with SCD. Nineteen hospitalized patients with SCD and parvovirus B19-induced TRCA were evaluated. Blood tests included CBC, flow cytometry, and total antibody isotype analyses. Cytokine/chemokine analyses were performed on nasal wash (NW) samples, representing a common site of viral entry. Unusually high white blood cell count (WBC) and absolute neutrophil count (ANC) values were observed in some patients. A correlation matrix with Day 0 values from the 19 patients then identified two mutually exclusive phenotype clusters. Cluster 1 included WBC, ANC, absolute reticulocyte count (ARC), absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), NW cytokines/chemokines, % naïve cells among B cell and T cell populations, and parvovirus-specific IgG. This cluster was negatively associated with virus load, suggesting a signature of successful adaptive immunity and virus control. Cluster 2 included virus load, % CD38CD24 cells among CD19 B cells (termed 'plasmablasts' for simplicity), % HLA-DR cells among CD19 B cells, IgG4, and % memory phenotypes among B cell and T cell populations. Plasmablast percentages correlated negatively with parvovirus-specific IgG, possibly reflecting a non-specific trigger of cell activation. All patients were released from the hospital within 1 week after admission, and the highest WBC and ANC values were eventually reduced. Nonetheless, a concern remained that the acutely abnormal immune profiles caused by parvovirus B19 infections could exacerbate chronic inflammation in some patients. To avoid the numerous sequelae known to affect patients with SCD following hospitalizations with parvovirus B19, rapid development of a parvovirus B19 vaccine is warranted.
细小病毒B19常感染儿童，并以红系谱系细胞为靶标。虽然健康儿童很少患重病，但患有镰状细胞病（SCD）的儿童在首次接触该病毒后可能会经历短暂红细胞再生障碍（TRCA）、住院以及危及生命的贫血。鉴于患有SCD的儿童也会遭受慢性炎症，且细小病毒B19在其他患者群体中与自身免疫性疾病有关，我们询问细小病毒B19感染是否会导致患有SCD的儿童出现急性和慢性免疫异常。对19名因细小病毒B19感染导致TRCA而住院的SCD患者进行了评估。血液检测包括全血细胞计数（CBC）、流式细胞术和总抗体亚型分析。对代表病毒进入常见部位的鼻洗液（NW）样本进行细胞因子/趋化因子分析。在一些患者中观察到白细胞计数（WBC）和绝对中性粒细胞计数（ANC）异常高。然后，根据19名患者第0天的值建立的相关矩阵确定了两个相互排斥的表型簇。簇1包括WBC、ANC、绝对网织红细胞计数（ARC）、绝对淋巴细胞计数（ALC）、乳酸脱氢酶（LDH）、NW细胞因子/趋化因子、B细胞和T细胞群体中幼稚细胞的百分比以及细小病毒特异性IgG。该簇与病毒载量呈负相关，表明是成功的适应性免疫和病毒控制的特征。簇2包括病毒载量、CD19 B细胞中CD38CD24细胞的百分比（为简单起见称为“浆母细胞”）、CD19 B细胞中HLA-DR细胞的百分比、IgG4以及B细胞和T细胞群体中记忆表型的百分比。浆母细胞百分比与细小病毒特异性IgG呈负相关，可能反映了细胞活化的非特异性触发因素。所有患者在入院后1周内出院，最高的WBC和ANC值最终下降。尽管如此，人们仍然担心细小病毒B19感染引起的急性免疫异常可能会加重一些患者的慢性炎症。为避免已知的细小病毒B19感染住院后影响SCD患者的众多后遗症，有必要迅速研发细小病毒B19疫苗。
