PMID- 33393636
OWN - NLM
STAT- MEDLINE
DCOM- 20210823
LR  - 20210823
IS  - 1462-0332 (Electronic)
IS  - 1462-0324 (Linking)
VI  - 60
IP  - 8
DP  - 2021 Aug 2
TI  - Interferon-related gene expression in response to TNF inhibitor treatment in 
      ankylosing spondylitis patients: a pilot study.
PG  - 3607-3616
LID - 10.1093/rheumatology/keaa817 [doi]
AB  - OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory arthritis 
      primarily affecting the spine and sacroiliac joints. TNF inhibitor (TNFi) drugs 
      are recommended for patients not responding to NSAIDs; however, there is a 
      significant need for biomarkers of response. IFN-regulated genes (IRGs) and other 
      cytokines/chemokines are linked to autoimmune diseases and have been associated 
      with treatment response. Our objective was to explore whether IRGs and 
      cytokines/chemokines can be associated with response to TNFiagents in AS. 
      METHODS: Peripheral blood mononuclear cells were obtained from 26 AS patients who 
      were to receive a TNFi (I, n = 15) or placebo (P, n = 11) at week 0 and week 22. 
      Response (R)/non-response (NR) was defined as reduction in ASDAS >/= 1.2 points or 
      reduction in sacroiliac/vertebral MRI lesions. The expression of 96 genes was 
      quantified using TaqMan assays. Finally, ELISA was used to measure IL-6 in serum 
      samples from another 38 AS patients. RESULTS: Analysis of gene expression in 26 
      baseline samples segregated patients into four groups defined by a signature of 
      15 genes (mainly IRGs). ASDAS response was associated with one group 
      independently of treatment received. We then analysed response to the TNFi 
      (n = 15) and identified a 12-gene signature associated with MRI response. A third 
      IRG signature was also associated with a reduction in IRGs expression post-TNFi 
      samples (n = 10 pairs). Finally, decreased circulating IL-6 was associated with 
      BASDAI-R. CONCLUSION: This pilot study suggests an association between IRG 
      expression and response to TNFi in AS. These findings require validation in a 
      larger cohort in order to construct predictive algorithms for patient 
      stratification.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      British Society for Rheumatology. All rights reserved. For permissions, please 
      email: journals.permissions@oup.com.
FAU - Harrison, Stephanie R
AU  - Harrison SR
AUID- ORCID: 0000-0002-7465-2621
AD  - University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, 
      Leeds, UK.
FAU - Burska, Agata N
AU  - Burska AN
AD  - University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, 
      Leeds, UK.
FAU - Emery, Paul
AU  - Emery P
AUID- ORCID: 0000-0002-7429-8482
AD  - University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, 
      Leeds, UK.
AD  - NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS 
      Trust, Leeds, UK.
FAU - Marzo-Ortega, Helena
AU  - Marzo-Ortega H
AUID- ORCID: 0000-0002-9683-3407
AD  - University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, 
      Leeds, UK.
AD  - NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS 
      Trust, Leeds, UK.
FAU - Ponchel, Frederique
AU  - Ponchel F
AUID- ORCID: 0000-0002-3969-7701
AD  - University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, 
      Leeds, UK.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Rheumatology (Oxford)
JT  - Rheumatology (Oxford, England)
JID - 100883501
RN  - 0 (Biomarkers)
RN  - 0 (Interferon Type I)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor Inhibitors)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers/blood
MH  - Female
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Interferon Type I/*metabolism
MH  - Interleukin-6/blood
MH  - Male
MH  - Middle Aged
MH  - Pilot Projects
MH  - Spondylitis, Ankylosing/*blood/drug therapy
MH  - Tumor Necrosis Factor Inhibitors/pharmacology/*therapeutic use
MH  - Young Adult
OTO - NOTNLM
OT  - ankylosing spondylitis
OT  - axial spondyloarthritis
OT  - gene expression signature
OT  - interferon
OT  - tumour necrosis factor inhibitor
EDAT- 2021/01/05 06:00
MHDA- 2021/08/24 06:00
CRDT- 2021/01/04 09:21
PHST- 2020/05/25 00:00 [received]
PHST- 2020/11/07 00:00 [revised]
PHST- 2021/01/05 06:00 [pubmed]
PHST- 2021/08/24 06:00 [medline]
PHST- 2021/01/04 09:21 [entrez]
AID - 6061532 [pii]
AID - 10.1093/rheumatology/keaa817 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2021 Aug 2;60(8):3607-3616. doi: 
      10.1093/rheumatology/keaa817.