Details

Autor(en) / Beteiligte

• Leong, Jing Yao
• Chen, Phyllis
• Yeo, Joo Guan
• Ally, Fauziah
• Chua, Camillus
• Nur Hazirah, Sharifah
• Poh, Su Li
• Pan, Lu
• Lai, Liyun
• Lee, Elene Seck Choon
• Bathi, Loshinidevi D/O Thana
• Arkachaisri, Thaschawee
• Lovell, Daniel
• Albani, Salvatore

Titel

Immunome perturbation is present in patients with juvenile idiopathic arthritis who are in remission and will relapse upon anti-TNFα withdrawal

Ist Teil von

• Annals of the rheumatic diseases, 2019-12, Vol.78 (12), p.1712-1721

Ort / Verlag

England: BMJ Publishing Group LTD

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• ObjectivesBiologics treatment with antitumour necrosis factor alpha (TNFα) is efficacious in patients with juvenile idiopathic arthritis (JIA). Despite displaying clinical inactivity during treatment, many patients will flare on 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.MethodsWe interrogated the circulatory reservoir of CD4+ immune subsets at the single-cell resolution with mass cytometry (cytometry by time of flight) of patients with JIA (n=20) who displayed continuous clinical inactivity for at least 6 months with anti-TNFα and were subsequently withdrawn from therapy for 8 months, and scored as relapse or remission.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 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.ResultsAn 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 (1) T-cell receptor activation, (2) apoptosis, (3) TNFα, (4) nuclear factor-kappa B and (5) mitogen-activated protein kinase signalling.ConclusionsA unique discriminatory immunomic and transcriptomic signature is associated with relapse patients and may explain how relapse occurs.