Plasma cytokine profiles in systemic sclerosis: associations with autoantibody subsets and clinical manifestations
IntroductionSystemic sclerosis (scleroderma, SSc) is a complex autoimmune disease that clinical manifests as progressive fibrosis of the skin and internal organs. Anti-centromere antibodies (ACA), anti-topoisomerase antibodies (ATA), and anti-RNA polymerase III antibodies (ARA) are three mutually exclusive SSc-associated autoantibodies that correlate with distinct clinical subsets characterized by extentof cutaneous involvement and pattern of organ involvement.
The current report sought to determine if plasma cytokine profiles differ in SSc patients grouped according to these SSc-associated autoantibodies subsets.
Methods: Plasma from 444 SSc patients and 216 healthy controls were obtained from the Scleroderma Family Registry and University of Texas Rheumatology Division. Patients were classified according to the presence of ACA, ATA, ARA, or none of the above (Ab-Neg).
Levels of 13 cytokines were determined using multiplex assays.
Results: Compared to females, healthy control males had higher plasma levels of interleukin (IL)-2 (P=0.008), IL-5 (P=0.01) and IL-8 (P=0.01). In addition, in controls, IL-6 (P=0.02) and IL-17 (P=0.01) levels increased with advancing age.
After adjusting for age and gender, SSc patients had higher circulating levels of tumor necrosis factor-alpha (TNF-alpha) (P<0.0001), IL-6 (P<0.0001), and interferon-gamma (IFN-g) (P=0.05) and lower IL-17 (P=0.0005) and IL-23 (P=0.014). Additional analyses demonstrated that disease duration also influenced these cytokine profiles.
IL-6 was elevated in ATA+ and ARA+ patients, but not in ACA+ patients. IL-8 was uniquely increased in the ATA+ subset while both ATA+ and ACA+ subsets had elevated IFN-g and IL-10.
IL-5 was only significantly increased in the ACA+ subset. Lastly, patients with interstitial lung disease had elevated IL-6 and patients with pulmonary hypertension had elevated IL-6 and IL-13.
Conclusions: Plasma cytokine profiles differ in SSc patients based on the presence of SSc-associated autoantibodies.
Plasma cytokine profiles in SSc patients may also be affected by disease duration and the pattern of internal organ involvement.
Author: Pravitt GourhFrank ArnettShervin AssassiFilemon TanMei HuangLaura DiekmanMaureen MayesJohn ReveilleSandeep Agarwal
Credits/Source: Arthritis Research &Therapy 2009, 11:R147
Published on: 2009-10-02
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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