ICMR-National Institute of Virology, Mumbai Unit, Formerly Enterovirus Research Centre, Indian Council of Medical Research, Mumbai, India.
ICMR-National Institute of Immunohaematology, Indian Council of Medical Research, KEM Hospital, Mumbai, India.
Front Immunol. 2019 Jul 23;10:1567. doi: 10.3389/fimmu.2019.01567. eCollection 2019.
The emergence of immunodeficiency-associated vaccine-derived polioviruses (iVDPV) from children with primary immunodeficiency disorders poses a threat to the eradication program. Herein, we report a patient with severe combined immunodeficiency (SCID), identified as a prolonged serotype 3 iVDPV (iVDPV3) excreter with 13 VDPV3 isolates and a maximum of 10.33% nucleotide divergence, who abruptly cleared infection after a period of 2 years. Occurrence of an episode of norovirus diarrhea associated with increased activated oligoclonal cytotoxic T cells, inverse CD4:CD8 ratio, significantly elevated pro-inflammatory cytokines, and subsequent clearance of the poliovirus suggests a possible link between inflammatory diarrheal illness and clearance of iVDPV. Our findings suggest that in the absence of B cells and sufficiently activated T/NK cells, macrophages and other T cells may produce auto-inflammatory conditions by TLR/RLR ligands expressed by previous/ongoing bacterial or viral infections to clear VDPV infection. The study highlights the need to screen all the patients with combined immunodeficiency for poliovirus excretion and intermittent follow-up of their immune parameters if found positive, in order to manage the risk of iVDPV excretion in the polio eradication endgame strategy.
免疫缺陷相关疫苗衍生脊灰病毒(iVDPV)由原发性免疫缺陷患儿产生,对消灭脊灰病毒计划构成威胁。本研究报告了 1 例严重联合免疫缺陷(SCID)患儿,该患儿被鉴定为持续性 3 型 iVDPV(iVDPV3)排泄者,携带 13 株 iVDPV3 分离株,核苷酸差异最大达 10.33%,在经历 2 年的持续排泄后,病毒感染突然清除。诺如病毒腹泻发作,同时伴有激活的寡克隆细胞毒性 T 细胞增加、CD4:CD8 比值倒置、促炎细胞因子显著升高,随后脊灰病毒被清除,这提示炎症性腹泻病与 iVDPV 清除之间可能存在关联。本研究结果表明,在缺乏 B 细胞和充分激活的 T/NK 细胞的情况下,巨噬细胞和其他 T 细胞可能通过 TLR/RLR 配体产生自身炎症状态,从而清除 VDPV 感染,这些配体由先前/正在进行的细菌或病毒感染表达。该研究强调,在消灭脊灰病毒终局战略中,需要对所有联合免疫缺陷患儿进行脊灰病毒排泄筛查,并对检测阳性者的免疫参数进行间歇性随访,以管理 iVDPV 排泄风险。