Intraepithelial CD15 infiltration identifies high-grade anal dysplasia in people with HIV

Abstract

Adaptive immunity; Immunology; Infectious disease

Immunitat adaptativa; Immunologia; Malaltia infecciosa

Inmunidad adaptativa; Inmunología; Enfermedad infecciosa

Men who have sex with men (MSM) with HIV are at high risk for squamous intraepithelial lesion (SIL) and anal cancer. Identifying local immunological mechanisms involved in the development of anal dysplasia could aid treatment and diagnostics. Here, we studied 111 anal biopsies obtained from 101 MSM with HIV, who participated in an anal screening program. We first assessed multiple immune subsets by flow cytometry, in addition to histological examination, in a discovery cohort. Selected molecules were further evaluated by immunohistochemistry in a validation cohort. Pathological samples were characterized by the presence of resident memory T cells with low expression of CD103 and by changes in natural killer cell subsets, affecting residency and activation. Furthermore, potentially immunosuppressive subsets, including CD15+CD16+ mature neutrophils, gradually increased as the anal lesion progressed. Immunohistochemistry verified the association between the presence of CD15 in the epithelium and SIL diagnosis for the correlation with high-grade SIL. A complex immunological environment with imbalanced proportions of resident effectors and immune-suppressive subsets characterized pathological samples. Neutrophil infiltration, determined by CD15 staining, may represent a valuable pathological marker associated with the grade of dysplasia.

The authors thank the study participants. We would also like to thank Cristina de Dios Conde and Marta Valeri Sala from the Microscopy platform at the High Technology Unit (UAT, VHIR) for excellent technical assistance. This work was primarily supported by grants from the Spanish Health Institute Carlos III (ISCIII, PI16/00736 and PI20/00160) and cofunded by ERDF/ESF, “A way to make Europe”/“Investing in your future.” This work was additionally supported in part by the Spanish AIDS network Red Temática Cooperativa de Investigación en SIDA (RD16/0025/0007), the Fundació La Marató TV3 (201814-10FMTV3), and the Gilead fellowships GLD18/00008. MJB is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179). NM was supported by a PhD fellowship from the VHIR. The funders had no role in study design, data collection and analysis, the decision to publish, or preparation of the manuscript.