RT Journal Article
SR Electronic
T1 An immunome perturbation is present in juvenile idiopathic arthritis patients who are in remission and will relapse upon anti-TNFα withdrawal
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 656124
DO 10.1101/656124
A1 Jing Yao Leong
A1 Phyllis Chen
A1 Joo Guan Yeo
A1 Fauziah Ally
A1 Camillus Chua
A1 Sharifah Nur Hazirah
A1 Su Li Poh
A1 Lu Pan
A1 Liyun Lai
A1 Elene Seck Choon Lee
A1 Loshinidevi D/O Thana Bathi
A1 PRCSG
A1 Thaschawee Arkachaisri
A1 Daniel J. Lovell
A1 Salvatore Albani
YR 2019
UL http://biorxiv.org/content/early/2019/05/31/656124.abstract
AB Objectives Biologics treatment with anti-TNFα is efficacious in juvenile idiopathic arthritic (JIA) patients. Despite displaying clinical inactivity during treatment, many patients will flare upon cessation of therapy. The inability to definitively discriminate patients who will relapse or continue to remain in remission after therapy withdrawal is currently a major unmet medical need. CD4 T cells have been implicated in active disease, yet how they contribute to disease persistence despite treatment is unknown.Methods We interrogated the circulatory reservoir of CD4+ immune subsets at the single cell resolution with mass cytometry (CyToF) of JIA patients (n=20) who displayed continuous clinical inactivity for at least 6 months with anti-TNFα, and were subsequently withdrawn from therapy for 8 months, and scored as relapse or remission. These patients were examined prior to therapy withdrawal for putative subsets that could discriminate relapse from remission. We verified on a separate JIA cohort (n=16), the continued dysregulation of these circulatory subsets 8 months into therapy withdrawal. The immunological transcriptomic signature of CD4 memory in relapse/remission patients was examined with Nanostring.Results An inflammatory memory subset of CD3+CD4+CD45RA−TNFα+ T cells deficient in immune checkpoints (PD1−CD152−) was present in relapse patients prior to therapy withdrawal. Transcriptomic profiling reveals divergence between relapse and remission patients in disease centric pathways involving (a) TCR activation, (b) apoptosis, (c) TNFα, (d) NF-kB and (e) MAPK signalling.Conclusions A unique discriminatory immunomic and transcriptomic signature is associated with relapse patients and may explain how relapse occurs.