Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
The Interferon Signature in Myositis Is Associated with RNA-Binding Protein Autoantibodies.
Bilgic4, Hatice, Wilson4, Joseph, Koeuth4, Thearith, McNallan2, Kelly T., Ytterberg1, Steven R., Peterson3, Erik J., Reed1, Ann M.
Several autoimmune diseases are characterized by elevated expression of type I interferon (IFN)-regulated transcripts and proteins in peripheral blood. This IFN signature' is a marker for disease activity in patients with dermatomyositis (DM), and IFN pathway activation is proposed to play a role in the pathogenesis of this disease. The IFN signature in systemic lupus erythematosus is associated with the presence of autoantibodies against RNA binding proteins (RBP), which are commonly observed in lupus patients. However, anti-RBP antibodies are found less frequently in patients with DM.
We compared blood IFN signatures and autoantibody profiles in 126 patients with inflammatory idiopathic myopathies (IIM), including 76 DM patients (46 adult and 30 pediatric) and 50 patients with other types of IIM (24 polymyositis (PM), 9 inclusion body myositis (IBM), and 17 with uncharacterized myositis). IFN gene signatures were measured from whole blood RNA using TaqMan quantitative real-time RT-PCR to detect the levels of 3 IFN-regulated transcripts (G1P2, IFIT1, and IRF7). For each subject, an IFN gene score' was calculated from the levels of these 3 transcripts. Serum levels of IFN-regulated chemokines (IP-10, I-TAC, and MCP-1) were measured using a multiplexed ELISA (SearchLight, Aushon Bioscience), and a chemokine score' was calculated for each patient using the normalized levels of the 3 chemokines. A bead-based immunoassay (Luminex) was used to detect anti-Sm, -RNP, -SS-A 60, -SS-A 52, -SS-B, -Scl-70, -Jo-1, -Ribosome P and -Chromatin antibodies in serum. Spearman's rank method was used to for correlation and the Mann-Whitney test was used for group comparisons.
Out of 126 myositis patients, 33 were positive for at least one RBP antibody (anti-Sm, -RNP, -SS-A, or SS-B). Both chemokine scores (p=0.04) and IFN gene scores (p=0.003) were significantly higher in RBP+ patients compared to RBP- patients. The IFN gene score was significantly correlated with the number of RBP antibodies (r=0.31, p=0.002), and with the levels of individual autoantibodies (anti-RNP, r=0.28, p=0.004; SS-A 60, r=0.23, p=0.02; and SS-A 52, r=0.35, p=0.0004). The chemokine score was positively correlated with anti-SS-A (r=0.20, p=0.02) but negatively correlated with anti-Sm (r =-0.18, p=0.04). When the analysis was repeated in the DM and other myositis' (PM, IBM, uncharacterized IIM) groups separately, IFN gene scores of RBP+ and RBP- groups were significantly different in both the DM and other myositis' subgroups (p=0.01 for both). IFN gene and chemokine scores were significantly correlated in the DM subgroup (r=0.61, p<0.001) but not in the others (r=0.11, p=0.59).
These results suggest that the IFN gene signature is associated with the presence of anti-RBP antibodies in patients with myositis. The presence of these autoantibodies, together with elevated IFN signatures, may promote identification of patients with myositis overlap syndromes.
To cite this abstract, please use the following information:
Bilgic, Hatice, Wilson, Joseph, Koeuth, Thearith, McNallan, Kelly T., Ytterberg, Steven R., Peterson, Erik J., et al; The Interferon Signature in Myositis Is Associated with RNA-Binding Protein Autoantibodies. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :934