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Serum CXCL10 levels are associated with better responses to abatacept treatment of rheumatoid arthritis


1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

 

  1. Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, and Division of Arthritis and Collagen Disease, Higashi-Hiroshima Memorial Hospital, Higashi-Hiroshima, Japan.
  2. Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan.
  3. Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan.
  4. Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan.
  5. Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan.
  6. Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan.
  7. Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan.
  8. Division of Arthritis and Collagen Disease, Higashi-Hiroshima Memorial Hospital, Higashi-Hiroshima, Japan.
  9. Division of Arthritis and Collagen Disease, Higashi-Hiroshima Memorial Hospital, Higashi-Hiroshima, Japan.
  10. Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan.
  11. Division of Arthritis and Collagen Disease, Higashi-Hiroshima Memorial Hospital, Higashi-Hiroshima, Japan.
  12. Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan. esugiyam@hiroshima-u.ac.jp

CER12689
2020 Vol.38, N°5
PI 0956, PF 0963
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PMID: 31969227 [PubMed]

Received: 19/08/2019
Accepted : 04/11/2019
In Press: 20/01/2020
Published: 02/10/2020

Abstract

OBJECTIVES:
This study aimed to identify therapeutic predictors of abatacept (ABT) treatment in rheumatoid arthritis (RA) in vitro and in patients.
METHODS:
T cell cytokine, monokine, and chemokine levels in culture supernatants or serum were determined using flow cytometry bead-based immunoassays. CXCL10 mRNA and protein expressions were also assessed using qPCR and ELISA analyses, respectively. In the patient study, 25 ABT-treated patients were analysed retrospectively. The patients were divided into low disease activity (LDA) or non-low disease activity (non-LDA) groups at 24 weeks of ABT treatment. Seven T cell cytokines and CXCL10 levels were compared in these two groups.
RESULTS:
Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated by immobilised anti-CD3 with or without ABT for three days, and the levels of 13 T cell cytokines in culture supernatants were determined. ABT significantly inhibited anti-CD3-induced production of IFN-γ. To examine the effect of these T cell cytokines in rheumatoid synovial cells (RSC), RSCs were stimulated with 10% of culture supernatants from anti-CD3-stimulated PBMCs with or without ABT, and the levels of 23 cytokines were determined. Only CXCL10 was significantly reduced by ABT-treated supernatants. In the patient study, CXCL10 levels at baseline were not different between the LDA and non-LDA groups, whereas CXCL10 levels at 24 weeks were significantly decreased in the LDA group only.
CONCLUSIONS:
ABT treatment significantly affected IFN-γ and CXCL10 cytokine levels in vitro. In addition, serum CXCL10 levels were associated with better responses in ABT treatment.

Rheumatology Article