Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Plasma Myeloperoxidase Activity Is Increased in Patients with RA Compared to Healthy Controls and Is Associated with Abnormal Anti-Inflammatory Function of High Density Lipoprotein

Charles-Schoeman1,  Christina, Lee1,  Yuen Yin, Amjadi1,  Sogol, McMahon2,  Maureen A., Paulus1,  Harold E., Reddy1,  Srinivasa T.

David Geffen School of Medicine at UCLA, Los Angeles, CA
Division of Rheumatology, David Geffen School of Medicine at UCLA, Los Angeles, CA

Purpose:

We have previously shown that abnormal anti-inflammatory function of high density lipoprotein (HDL) in RA patients is associated with high levels of systemic inflammation and an altered HDL-associated protein cargo. Myeloperoxidase (MPO) is a heme peroxidase abundant in activated neutrophils which has been shown to inhibit HDL function by oxidatively modifying apolipoprotein A-1 (apoA-1). Systemic MPO levels predict the presence and extent of coronary artery disease in the general population. The current work investigates whether plasma MPO activity is increased in RA patients compared to healthy controls, and whether higher MPO activity is associated with worse anti-inflammatory function of HDL in patients with RA.

Methods:

40 patients with RA were compared with 40 age and sex matched healthy controls. Plasma MPO activity was assessed by a commercially available colorimetric assay which uses a polyclonal antibody specific for human MPO. HDL's anti-inflammatory function was assessed by a previously published cell free assay which assesses the ability of patient HDL to inhibit oxidation of a stock LDL. Plasma levels of ApoA1 were assessed by standard ELISA and paraoxanase-1 (PON-1) activity was measured by a previously described arylesterase assay.

Results:

Patient characteristics are described in the table below. Plasma MPO activity was higher in RA patients compared to healthy controls and was significantly correlated with HDL function in patients with RA (r = 0.41/p=0.009); higher plasma MPO activity was associated with worse HDL anti-inflammatory function as measured by the HDL inflammatory index (HII). Both MPO activity and HDL function were significantly correlated with RA disease activity measured by the DAS28 (r = 0.45 and 0.42 respectively, p values<0.008). Higher RA disease activity was associated with higher MPO activity and worse HDL function. The activity of PON-1, an anti-oxidant enzyme associated with HDL, was lower in RA patients compared to healthy controls (p=0.03). There were no significant differences in quantitative HDL, LDL, or ApoA-1 levels between the two groups.

GroupHIIAge (yrs)F (%)HSCRP (mg/L)ESR (mm/h)HDL (mg/dL)LDL (mg/dL)ApoA-1 (ug/ml)MPO (ng/ml)PON (mOD/min)
RA0.84 ± 0.87*56 ± 12855.7 ± 8.7*28 ± 26*60 ± 20103 ± 37209 ± 10931.7 ± 24.5*3.9 ± 1.2*
Control0.32 ± 0.1952 ± 13801.8 ± 2.514 ± 1059 ± 18114 ± 35190 ± 7720.5 ± 15.35.0 ± 2.1
F=Female; HII=HDL Inflammatory Index; *p value < 0.05 compared to controls.

To cite this abstract, please use the following information:
Charles-Schoeman, Christina, Lee, Yuen Yin, Amjadi, Sogol, McMahon, Maureen A., Paulus, Harold E., Reddy, Srinivasa T.; Plasma Myeloperoxidase Activity Is Increased in Patients with RA Compared to Healthy Controls and Is Associated with Abnormal Anti-Inflammatory Function of High Density Lipoprotein [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1630
DOI: 10.1002/art.26704

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