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.
Interferon-Alpha Activation in Relation to Pro-Inflammatory Cytokines and Anti-Ro/La Response in Primary Sjgren's Syndrome.
Nossent1, Johannes C., Rischmueller2, Maureen, Becker-Merok1, Andrea, Lester2, Sue
University of Tromsø, Tromso, Norway
Queen Elizabeth Hospital, Adelaide, Australia
Background/Purpose:
Interferon type I activation is a major pathway in the pathogenesis of systemic autoimmune diseases. While up regulation of type I IFN genes has been described in salivary glands and PBMC, there are few data on circulating IFNa2 in primary Sjøgren's syndrome (pSS). We investigated the frequency, clinical and serological correlates of increased levels of circulating IFNa2 in pSS patients.
Methods:
Cross sectional study of patients with established pSS (n= 83). Healthy controls (HC) (n= 27) and patients with Systemic lupus Erythematosus (SLE) (n=87) served as comparators.Cytokine levels were determined on stored sera by a highly sensitive seven-plex bead immunoassay with BAFF measured by commercial ELISA. Associations between increased IFN-a, clinical measures and serological biomarkers were analyzed by nonparametric methods.
Results:
IFNa2 was increased in 48.2% of pSS patients versus 64.4% in SLE (p=0.03) and 7.2% in HC (p<0.01). pSS patients with increased IFNa had significantly higher levels of IL-1b, IL-6, IL-10, IL-12, TNFa and GM-CSF, while IL-15 and BAFF did not differ from patients with normal IFNa (51.8%). In pSS patient with increased IFNa2 levels, the mean number of elevated cytokines was five (range 1–8) versus 0.5 (range 0–3) in patients with normal IFNa2 (p<0.001). Increased IFNa2 did not associate with scores for fatigue, sleepiness or urogenital symptoms, low C4 or leucopenia, but was associated with increasing diversity of the anti-Ro/La antibody response (p=0.04 for linear trend) and higher titers of IgG and RF. In the 43 patients with normal IFNa2, there was no activation of other cytokines in 24 (56%) with increased BAFF (30%) and IL-6 (18%) accounting for most cytokine abnormailities in this group.
Conclusion:
High circulating levels of IFNa2 are found in nearly half of all pSS patients, where they are accompanied by multiple cytokine activation and a diversified anti-Ro/La response. In the remaining pSS patients cytokine activation is uncommon suggesting a different underlying pathophysiology.
To cite this abstract, please use the following information:
Nossent, Johannes C., Rischmueller, Maureen, Becker-Merok, Andrea, Lester, Sue; Interferon-Alpha Activation in Relation to Pro-Inflammatory Cytokines and Anti-Ro/La Response in Primary Sjgren's Syndrome. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :486
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