HLA-DRB1*15:01 and the <i>MERTK</i> Gene Interact to Selectively Influence the Profile of MERTK-Expressing Monocytes in Both Health and MS
Michele D. Binder, Eze Nwoke, Ellen Morwitch, Chris Dwyer, Vivien Li, Alexandre Xavier, Rod A. Lea, Jeannette Lechner‐Scott, Bruce Taylor, Anne‐Louise Ponsonby, Trevor J. Kilpatrick, for the Ausimmune Investigator Group
Abstract
BACKGROUND AND OBJECTIVES: monocytes; cells with phagocytic and immunomodulatory potential. We aimed to understand how drivers of disease risk and pathogenesis vary with HLA and MERTK genotype and disease activity. METHODS: gene was assessed in whole blood samples of individuals experiencing their first episode of clinical CNS demyelination (n = 204) and matched HCs (n = 345) using an Illumina EPIC array. RESULTS: gene was significantly associated with the presence of DR15. DISCUSSION: gene provides a molecular link between these loci and identifies a potential mechanism by which MERTK expression is influenced by DR15. This links DR15 haplotype to MS susceptibility beyond direct influence on antigen presentation and suggests the need for HLA-based stratification of approaches to MERTK as a therapeutic target.