Decreased serum cell-free DNA levels in rheumatoid arthritis.

Marina Dunaeva,Ger J M Pruijn,René E M Toes,Erik Lubberts,Jolanda J Luime,Bastiaan C Buddingh’

doi:10.1007/s13317-015-0066-6

Abstract

PurposeRecent studies have demonstrated that serum/plasma DNA and RNA molecules in addition to proteins can serve as biomarkers. Elevated levels of these nucleic acids have been found not only in acute, but also in chronic conditions, including autoimmune diseases. The aim of this study was to assess cell-free DNA (cfDNA) levels in sera of rheumatoid arthritis (RA) patients compared to controls.MethodscfDNA was extracted from sera of patients with early and established RA, relapsing-remitting multiple sclerosis patients (RRMS) and healthy subjects, and its concentration was determined by quantitative PCR using two amplicons, Alu115 and β-actin205, corresponding to Alu repetitive elements and the β-actin single-copy gene, respectively. Serum DNase activity was measured by a single radial enzyme diffusion method.ResultsReduced levels of cfDNA were observed in patients with established RA in comparison with healthy controls, early RA patients and RRMS patients. There were no significant differences in cfDNA concentration between healthy controls, early RA and RRMS patients. Total DNase activity appeared to be similar in the sera of all tested groups.ConclusionsOur results demonstrate that cfDNA levels are strongly reduced in the sera of established RA patients, which is not caused by changes in DNase activity. Measurement of cfDNA can distinguish established RA patients from early RA patients. Thus, cfDNA may serve as a biomarker in RA.Electronic supplementary materialThe online version of this article (doi:10.1007/s13317-015-0066-6) contains supplementary material, which is available to authorized users.

Highlights

Rheumatoid arthritis (RA) is a chronic heterogeneous autoimmune disease characterized by progressive joint destruction
Reduced levels of cell-free DNA (cfDNA) were observed in patients with established rheumatoid arthritis (RA) in comparison with healthy controls, early RA patients and relapsing-remitting multiple sclerosis patients (RRMS) patients
In addition to sera from established RA (esRA) patients, sera from healthy individuals and from RRMS patients were used as controls; RRMS was chosen as another autoimmune disease with a different disease onset and with different treatment strategies

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic heterogeneous autoimmune disease characterized by progressive joint destruction. Serological tests, most notably the detection of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF), play an important role in diagnosing RA. ACPA were found in up to 75 % of RA patients [1]. RF is present in 60–90 % of patients with established RA (esRA) and in up to 50 % of patients with early RA (eRA) [2]. In contrast to ACPA the disease specificity of RF is relatively low, with 3–5 % of healthy adults showing the presence of RF in their serum, which increases to 10–30 % in the elderly [3]. RF was found in patients with other autoimmune and infectious diseases

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