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

• Published in: Rheumatology (Oxford, England) England), 2011-04, Vol.50 (4), p.721-728
• Main Authors: CANETE, Juan D, ALBALADEJO, Carolina, SANMARTI, Raimon, VICTORIA HERNANDEZ, Maria, LAINEZ, Begona, PINTO, Jose A, RAMIREZ, Julio, JOSE LOPEZ-ARMADA, Maria, RODRIGUEZ-CROS, Jose R, ENGEL, Pablo, BLANCO, Francisco J
• Format: Article
• Language: English
• Subjects: Adult; Alternative splicing; Alternative Splicing - physiology; Antibodies, Monoclonal - therapeutic use; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - diagnostic imaging; Arthritis, Rheumatoid - drug therapy; Biological and medical sciences; Biomarkers - blood; Cohort Studies; Disease Progression; Diseases of the osteoarticular system; Dose-Response Relationship, Drug; Female; Gold; Humans; Inflammatory joint diseases; Infliximab; Interstitial collagenase; Longitudinal Studies; Male; Matrix metalloproteinase; Matrix Metalloproteinase 1 - blood; Medical sciences; Methotrexate - therapeutic use; Middle Aged; Monoclonal antibodies; Prospective Studies; Radiography; Receptors, Tumor Necrosis Factor, Type II - blood; Receptors, Tumor Necrosis Factor, Type II - genetics; Rheumatism; Rheumatoid arthritis; Salts; Serum levels; Treatment Outcome; Tumor necrosis factor- alpha; Tumor Necrosis Factor-alpha - antagonists & inhibitors
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/keq381

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. 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. 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. 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.