美国国立卫生研究所Andrea Lisco团队研究了自然杀伤细胞功能恢复治疗复发性HPV疾病的效果。2021年9月1日出版的《新英格兰医学杂志》发表了这项成果。

人类乳头瘤病毒（HPV）感染是一系列良性和恶性上皮疾病的基础。研究组报道了一名青年男子病例，他在青春期患有由单纯疱疹病毒引起的脑炎，目前表现为由HPV引起的多发性复发性皮肤和粘膜病变。

研究组发现该患者在X-连锁白细胞介素-2受体亚单位γ基因（IL2RG）中存在致病性种系突变，在T细胞中发生体细胞恢复，但在自然杀伤（NK）细胞中未发生。异基因造血细胞移植导致NK细胞毒性恢复，皮肤微生物组正常化，所有HPV相关疾病持续缓解。NK细胞毒性似乎在抑制HPV定植和随后的HPV相关增生或发育异常病变中发挥作用。

附：英文原文

Title: Treatment of Relapsing HPV Diseases by Restored Function of Natural Killer Cells

Author: Andrea Lisco, M.D., Ph.D.,, Amy P. Hsu, B.S.,, Dimana Dimitrova, M.D.,, Diana M. Proctor, Ph.D.,, Emily M. Mace, Ph.D.,, Peiying Ye, Ph.D.,, Megan V. Anderson, R.N., B.A.,, Stephanie N. Hicks, R.N., B.S.N.,, Christopher Grivas, B.S.,, Dima A. Hammoud, M.D.,, Maura Manion, M.D.,, Gabriel J. Starrett, Ph.D.,, Alvin Farrel, Ph.D.,, Kerry Dobbs, M.S.,, Isaac Brownell, M.D., Ph.D.,, Christopher Buck, Ph.D.,, Luigi D. Notarangelo, M.D.,, Jordan S. Orange, M.D., Ph.D.,, Warren J. Leonard, M.D.,, Michael I. Orestes, M.D.,, Anju T. Peters, M.D.,, Jennifer A. Kanakry, M.D.,, Julia A. Segre, Ph.D.,, Heidi H. Kong, M.D.,, and Irini Sereti, M.D., M.H.S.

Issue&Volume: 2021-09-01

Abstract:

SummaryHuman papillomavirus (HPV) infections underlie a wide spectrum of both benign and malignant epithelial diseases. In this report, we describe the case of a young man who had encephalitis caused by herpes simplex virus during adolescence and currently presented with multiple recurrent skin and mucosal lesions caused by HPV. The patient was found to have a pathogenic germline mutation in the X-linked interleukin-2 receptor subunit gamma gene (IL2RG), which was somatically reverted in T cells but not in natural killer (NK) cells. Allogeneic hematopoietic-cell transplantation led to restoration of NK cytotoxicity, with normalization of the skin microbiome and persistent remission of all HPV-related diseases. NK cytotoxicity appears to play a role in containing HPV colonization and the ensuing HPV-related hyperplastic or dysplastic lesions.

DOI: 10.1056/NEJMoa2102715

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2102715