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Published on: February 14, 2025
Treatment of Relapsing HPV Diseases by Restored Function of Natural Killer Cells
Andrea Lisco1, Amy P Hsu1, Dimana Dimitrova1
1From the Laboratories of Immunoregulation (A.L., P.Y., M.V.A., C.G., M.M., I.S.) and Clinical Immunology and Microbiology (A.P.H., K.D., L.D.N.), National Institute of Allergy and Infectious Diseases, the Experimental Transplantation and Immunotherapy Branch (D.D., S.N.H., J.A.K.) and the Laboratory of Cellular Oncology (G.J.S., C.B.), National Cancer Institute, the Translational and Functional Genomics Branch, National Human Genome Research Institute (D.M.P., J.A.S.), the Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute (A.F., W.J.L.), the Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (H.H.K., I.B.), and the Center for Infectious Disease Imaging (D.A.H.), National Institutes of Health, and Walter Reed National Military Medical Center (M.I.O.) - all in Bethesda, MD; Vagelos College of Physicians and Surgeons, Columbia University, New York (E.M.M., J.S.O.); and the Department of Medicine and Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago (A.T.P.).
Abstract:
Human 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. (Funded by the National Institutes of Health and the Herbert Irving Comprehensive Cancer Center Flow Cytometry Shared Resources.).
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