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.
OBJECTIVE
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.
Rheumatology Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain. jcanete@clinic.ub.es
Juan D
JD
Cañete
Carolina
C
Albaladejo
Maria Victoria
MV
Hernández
Begoña
B
Laínez
José A
JA
Pinto
Julio
J
Ramírez
Maria José
MJ
López-Armada
José R
JR
Rodríguez-Cros
Pablo
P
Engel
Francisco J
FJ
Blanco
Raimon
R
Sanmartí
D000328:Adult; D017398:Alternative Splicing / Q000502:physiology*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000000981:diagnostic imaging / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000069285:Infliximab; D008137:Longitudinal Studies; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D011859:Radiography; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood* / Q000235:genetics; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D020781:Matrix Metalloproteinase 1; D008727:Methotrexate