Abstract

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. To investigate whether serum levels of HP are associated with the response of 12weeks MTX therapy in recent-onset RA patients. Sixty-nine active RA patients with recent onset (<24months) 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. After 12weeks 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±159.8mg/dL) compared to those in responders (255.3±143.9mg/dL) (P=0.01). Serum HP levels were decreased significantly from 255.3±143.9mg/dL at baseline to 186.4±108.5mg/dL at week 12 (P=0.04) in responders, but remained at high levels in non-responders. High serum levels of HP at baseline are associated with inadequate response of 12weeks 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.

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