Plasma cytokine profiles in systemic sclerosis: associations with autoantibody subsets and clinical manifestations

系统性硬化症的血浆细胞因子谱:与自身抗体亚群和临床表现的关系

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作者:Pravitt Gourh, Frank C Arnett, Shervin Assassi, Filemon K Tan, Mei Huang, Laura Diekman, Maureen D Mayes, John D Reveille, Sandeep K Agarwal

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.

Methods

Plasma from 444 SSc patients and 216 healthy controls was obtained from the Scleroderma Family Registry and University of Texas Rheumatology Division. Patients were classified according to the presence of ACAs, ATAs, ARAs, or none of the above (antibody-negative). Levels of 13 cytokines were determined using multiplex assays.

Results

Compared with females, healthy control males had higher plasma levels of 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 TNFalpha (P < 0.0001), IL-6 (P < 0.0001), and IFNgamma (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-positive and ARA-positive patients, but not in ACA-positive patients. IL-8 was uniquely increased in the ATA-positive subset while both ATA-positive and ACA-positive subsets had elevated IFNgamma and IL-10. IL-5 was only significantly increased in the ACA-positive 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.

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