Cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq) of peripheral blood to dissect the effect of different spondyloarthropathies

Abstract

Abstract Spondyloarthritis is a family of immune mediated inflammatory disorders with overlapping articular and extraarticular clinical manifestations and a strong association to human leukocyte antigen (HLA)-B27. Despite a strong association of HLA-B27 with prototypic spondyloarthropathies such as axial spondyloarthritis (axSpA) and acute anterior uveitis (AAU), the underlying mechanisms are not known. Here, we aim to determine whether HLA-B27 associated axSpA and AAU are associated with common or divergent immunological markers in the blood. Previously, we did single cell RNA-seq analysis on a small number of patients with AAU and axSpA, which revealed increase in T cell, MAIT cells and NK cell clusters in AAU patients, whereas axSpA patients had increase in MAIT cells, gd-T cells, ILCs and Tregs and decrease in naïve CD8 T cell clusters, suggesting that distinct signatures maybe associated with axSpA and AAU. Changes in ILCs or MAIT cells may suggest involvement of the gut mucosal surface in pathogenesis. This is consistent with our previous studies showing gut microbial perturbation in clinical samples and in rat model of spondyloarthritis. Leveraging on our preliminary data, we are performing CITE-seq to capture paired transcriptome and cell surface epitope expression in individual PBMCs from 5 subjects each with axSpA, AAU and axSpA+AAU in comparison with healthy individuals (5 HLA-B27 negative and 5 HLA-B27 positive). Since, HLA-B27 allele is also present in healthy population, these analyses will allow us to dissect the effect of host genetics from the disease. These studies represent potential advances in the understanding of spondyloarthritis and may reveal genetic and disease biomarkers associated with axSpA and AAU. TG (principal investigator) is a recipient of research awards from the Spondylitis Association of America, SPARTAN (Spondyloarthritis Research and Treatment Network), GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis), The Collins Medical Trust, Medical Research Foundation of Oregon and, Innovation Award from OHSU. This work was funded in part by the Grandmaison Fund for Autoimmunity Research. JTR is a recipient of the Innovative Research Award, Rheumatology Research Foundation.