High serum level of haptoglobin is associated with the response of 12 weeks methotrexate therapy in recent-onset rheumatoid arthritis patients

Abstract

Background: We previously found, using microarray, haptoglobin (HP) expression signal was 5.1-fold increased in peripheral blood mononuclear cells (PBMCs) from methotrexate (MTX)-resistant rheumatoid arthritis (RA) patients.

Objectives: To investigate whether serum levels of HP are associated with the response of 12 weeks MTX therapy in recent-onset RA patients.

Methods: Sixty-nine active RA patients with recent onset (< 24 months) were treated with MTX. Clinical variables, levels of HP messenger RNA (mRNA) in PBMCs and HP serum levels were tested at week 0 and week 12.

Results: After 12 weeks of MTX treatment, 34.7% of RA patients were categorized as responders according to European League Against Rheumatism (EULAR) response criteria (Week 12 Disease Activity Score of 28 joints [DAS-28] ≤ 3.2 and decrease > 1.2) and all others (65.2%) were defined as non-responders. The baseline HP mRNA in PBMCs from non-responders is significantly higher than those in responders (P < 0.05). Similar to mRNA expression, non-responders showed significantly elevated serum HP levels at baseline (369.9 ± 159.8 mg/dL) compared to those in responders (255.3 ± 143.9 mg/dL) (P = 0.01). Serum HP levels were decreased significantly from 255.3 ± 143.9 mg/dL at baseline to 186.4 ± 108.5 mg/dL at week 12 (P = 0.04) in responders, but remained at high levels in non-responders.

Conclusions: High serum levels of HP at baseline are associated with inadequate response of 12 weeks MTX treatment in recent-onset RA patients. Further replication studies in larger samples are needed to validate HP as a potential predictive biomarker for response to MTX therapy in RA.

Keywords: haptoglobin; methotrexate; rheumatoid arthritis.