Clinical significance of high levels of soluble tumour necrosis factor-α receptor-2 produced by alternative splicing in rheumatoid arthritis: a longitudinal prospective cohort study

Rheumatology (Oxford). 2011 Apr;50(4):721-8. doi: 10.1093/rheumatology/keq381. Epub 2010 Dec 6.


Objectives: We investigated whether serum levels of an alternatively spliced soluble (s)TNF receptor-2 (DS-TNFR2) affected the clinical response to anti-TNF-α therapy, classical DMARDs or radiological evidence of disease progression in patients with RA.

Methods: We included 116 patients with RA. Cohort 1: 52 DMARD-naïve early RA patients [mean (s.d.) disease duration 8.5 (6.2) months] who started gold salts and MTX therapies. Cohort 2: 64 MTX-resistant established RA patients [144 (107) months] who started infliximab therapy. We evaluated the European League Against Rheumatism (EULAR) response to therapy and the serum levels of DS-TNFR2, sTNFR2 and ACPAs at baseline and at 12 months. In Cohort 1, radiological progression and levels of MMP-1 were also determined.

Results: In Cohort 1, 40% of patients had high baseline levels (HL > 50 ng/ml) of DS-TNFR2 with significantly higher RF and ACPA levels than patients with normal levels (NL ≤ 50 ng/ml) of DS-TNFR2. The EULAR response to DMARDs was similar in HL and NL patients. Radiographic progression was observed in 23.5% of all patients after 12 months. In Cohort 2, 26.6% of patients had HL of DS-TNFR2 with significantly higher RF and ACPA levels than patients with NLs. The EULAR response from 6 to 30 weeks was prolonged in the HL group compared with the NL group.

Conclusions: Patients with HL of DS-TNFR2 maintained a prolonged therapeutic response to anti-TNF-α therapy and had proportionally less radiographic progression compared with patients with NLs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alternative Splicing / physiology*
  • Antibodies, Monoclonal / therapeutic use
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / drug therapy*
  • Biomarkers / blood
  • Cohort Studies
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infliximab
  • Longitudinal Studies
  • Male
  • Matrix Metalloproteinase 1 / blood
  • Methotrexate / therapeutic use
  • Middle Aged
  • Prospective Studies
  • Radiography
  • Receptors, Tumor Necrosis Factor, Type II / blood*
  • Receptors, Tumor Necrosis Factor, Type II / genetics
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors


  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Biomarkers
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Matrix Metalloproteinase 1
  • Methotrexate