Immunopathogenesis of skin and mucosal Human Papillomavirus (HPV)-related diseases

National Institute Of Allergy And Infectious Diseases

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Abstract

The studies on the immunological and genetic determinants of HPV-related diseases have further elucidated the role of CD4 T cells and NK cells in the development and clinical progression of HPV-related skin and mucosal diseases. In particular, we have been investigating the epidemiological and immunological characteristics of HPV anogenital colonization in HIV-1 infected women and man who have sex with man (MSM). In parallel, we delineated the immunological determinants of HPV pathogenesis in clinical models of primary immunodeficiencies with discrete genetic immunological defects. We reported on the clinical and immunological defects associated with a novel genetic variant causing a complete multilineage loss of expression of the CD4 molecule and the role NK mediated cytotoxicity in the context of a novel IL-2RG missense variant with somatic reversion. Such studies illustrated the role of specific immunological effector functions as well as the role of a reduced intensity conditioning allogeneic bone marrow transplantation (BMT) in leading to stable regression of recurrent HPV-related diseases. Novel metagenomic tools for HPV genotyping have been integrated with studies on the immunological function associated with control of HPV replication in the skin and in the anogenital compartment. The clinical and regulatory infrastructure to evaluate patients with skin and anogenital HPV-related disease has been further expanded focusing on patients with primary immunodeficiencies, idiopathic CD4 lymphopenia (ICL) and HIV/AIDS while a novel clinical protocol using long-acting rhIL-7 has been launched in a patient with ICL and refractory skin and mucosal HPV-related diseases.