Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


-Defensin-1 Is Increased in the Synovial Fluid of Rheumatoid Arthritis Patients and Induces IL-6 and IL-8 Expression in Fibroblast-Like Synoviocytes.

Ahn1,  Joong Kyong, Hwang2,  Jiwon, Lee2,  Jaejoon, Lee3,  You Sun, Jeon4,  Chan Hong, Koh2,  Eun-Mi, Cha2,  Hoon-Suk

Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
Samsung Medical Center, Sunkyunkwan University School of Medicine, Seoul, South Korea
Samsung Changwon Hospital, Changwon, South Korea
Soonchunhyang University College of Medicine, Bucheon, South Korea

Background/Purpose:

Fibroblast-like synoviocytes (FLS) play an essential role in the pathophysiology of rheumatoid arthritis (RA). Neutrophils are the most abundant cell type in the acute synovial effusion of RA patients. a-defensin-1 is released into the extracellular milieu from neutrophils during inflammation. Little is known about the role of a-defensin-1 for the development of joint inflammation in RA. Thus, we assessed the concentration of a-defensin-1 in synovial fluid (SF) of RA patients and osteoarthritis (OA) patients and evaluated the association between its concentration and clinical characteristics. We also investigated the effect of a-defensin-1 on the expression of IL-6 and IL-8 in rheumatoid FLS.

Methods:

The concentrations of SF a-defensin-1 from 51 RA patients and 21 OA patients were measured using ELISA. Real-time PCR was performed to measure the expression of IL-6 and IL-8 mRNA at 8 hours after stimulation with a-defensin-1(15 ug/ml) in rheumatoid FLS (n=5).

Results:

Patients with RA were composed of 47 female (92.1%) and 4 male patients, with a mean age of 54.3 ± 1.8 years, and mean disease duration of 81.1 ± 9.9 months. Forty-one patients (80.4%) were rheumatoid factor positive. Thirty-three patients (64.7%) had erosion on radiographic imaging. The SF a-defensin-1 concentration was significantly increased in RA patients compared to OA patients (39.3 ± 3.5 vs. 18.0 ± 5.6 ng/ml, p=0.002). Seropositive RA patients had significantly higher concentration of SF a-defensin-1 compared to seronegative patients (43.1 ± 3.8 vs. 20.8 ± 5.0 ng/ml, p=0.006). RA patients with ESR>50mm/hr or CRP>2mg/dl had significantly higher concentration of SF a-defensin-1 compared to patients with lower level of ESR or CRP, respectively (46.0 ± 3.9 vs. 21.7 ± 5.0 ng/ml, p=0.001; 48.2 ± 4.4 vs. 29.2 ± 4.7 ng/ml, p=0.005). SF a-defensin-1 concentration was more increased in RA patients with erosive change than non-erosive patients (43.1 ± 4.2 vs. 32.2 ± 5.8 ng/ml), although this difference did not reach statistical significance. There was no significant difference in SF a-defensin-1 level according to disease duration and age at disease onset. Both IL-6 and IL-8 mRNA expressions were significantly increased (13.34 ± 22.89-fold increase and 2.89 ± 1.49-fold increase, respectively, p <0.05) at 8 hrs after a-defensin-1 stimulation in rheumatoid FLS.

Conclusion:

SF a-defensin-1 concentration is increased in RA patients, especially in patients with positive RF and higher level of ESR and CRP. a-defensin-1 induced proinflammatory cytokine expression in RA FLS. These findings suggest that a-defensin-1 may play an important role as a potential inflammatory mediator for the development of joint inflammation in RA.

To cite this abstract, please use the following information:
Ahn, Joong Kyong, Hwang, Jiwon, Lee, Jaejoon, Lee, You Sun, Jeon, Chan Hong, Koh, Eun-Mi, et al; -Defensin-1 Is Increased in the Synovial Fluid of Rheumatoid Arthritis Patients and Induces IL-6 and IL-8 Expression in Fibroblast-Like Synoviocytes. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :377
DOI:

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