Abnormal function of high-density lipoprotein is associated with poor disease control and an altered protein cargo in rheumatoid arthritis

Arthritis Rheum. 2009 Oct;60(10):2870-9. doi: 10.1002/art.24802.


Objective: To characterize the antiinflammatory function of high-density lipoprotein (HDL) in patients with rheumatoid arthritis (RA) and to identify specific differences in HDL-associated proteins and enzymes that distinguish proinflammatory HDL from normal, antiinflammatory HDL.

Methods: We studied 132 RA patients. The antiinflammatory function of HDL was assessed by a cell-free assay, and proinflammatory HDL was defined by an HDL inflammatory index > or =1. Plasma and HDL-associated protein levels of apolipoprotein A-I (Apo A-I), haptoglobin, hemopexin, hemoglobin, and myeloperoxidase (MPO) were measured by direct and sandwich enzyme-linked immunosorbent assays, respectively. Lecithin:cholesterol acyltransferase (LCAT) activity was measured by a commercially available assay.

Results: Age, disease activity, the presence of erosive disease, non-Caucasian race, and smoking were significantly associated with proinflammatory HDL on multivariate analysis. Patients with proinflammatory HDL had higher measures of systemic inflammation, and a significant correlation was observed between RA disease activity (using the Disease Activity Score in 28 joints) and the HDL inflammatory index (r = 0.54, P < 0.0001). Compared with patients with antiinflammatory HDL, patients with proinflammatory HDL had significantly higher levels of haptoglobin, hemoglobin, Apo A-I, and MPO associated with HDL (P < 0.05 for all comparisons except MPO, which was P = 0.05). LCAT activity was lowest in patients with proinflammatory HDL, but was also significantly reduced in RA patients with antiinflammatory HDL as compared with healthy controls (P = 0.001).

Conclusion: Proinflammatory HDL in this RA patient cohort was associated with active disease and an altered protein cargo as compared with antiinflammatory HDL in RA patients and in healthy controls. The antiinflammatory function of HDL was inversely correlated with systemic inflammation in RA patients and may warrant further investigation as a mechanism by which active RA increases cardiovascular morbidity and mortality.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / therapeutic use
  • Apolipoprotein A-I / metabolism*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / metabolism*
  • Case-Control Studies
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Haptoglobins / metabolism*
  • Hemoglobins / metabolism*
  • Hemopexin / metabolism
  • Humans
  • Lipoproteins, HDL / metabolism*
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Peroxidase / metabolism*
  • Phosphatidylcholine-Sterol O-Acyltransferase / metabolism
  • Severity of Illness Index


  • Antirheumatic Agents
  • Apolipoprotein A-I
  • Haptoglobins
  • Hemoglobins
  • Lipoproteins, HDL
  • Hemopexin
  • Peroxidase
  • Phosphatidylcholine-Sterol O-Acyltransferase
  • Methotrexate