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.
BAFF Expression Correlates with Idiopathic Inflammatory Myopathy Disease Activity Measures, Interferon Signature and Autoantibodies.
McNallan1, Kelly T., Bilgic3, Hatice, Crowson2, Cynthia S., Ytterberg2, Steven R., Amin2, Shreyasee, Erik3, Peterson J., Baechler3, Emily C.
We have previously reported increased mRNA levels of B cell survival cytokines, B cell activating factor (BAFF) and its splice isoform transcript DBAFF, in blood cells of patients with idiopathic inflammatory myopathies (IIM.) Elevated BAFF and BAFF receptor levels influence increased survival of autoreactive B cells. We therefore investigated the relation of disease activity, autoantibody profiles and interferon pathway activation in IIM to B cell survival cytokines [BAFF, DBAFF and a proliferation inducing ligand (APRIL)] and their receptor expressions [BAFF receptor (BAFFR), transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA)].
RNA was extracted from whole blood in 108 IIM subjects (74 adult and juvenile dermatomyositis, 25 polymyositis and 9 inclusion body myositis). Gene expression of BAFF, DBAFF, APRIL, BCMA, TACI, BAFFR and three type I interferon (IFN)-regulated genes were measured by quantitative real-time RT-PCR. The whole-blood IFN gene expression signature was defined by average expression levels of 3 IFN-regulated genes (G1P2, IFIT1 and IRF7). Autoantibodies including Jo-1, Scl-70, Ribosome P, Chromatin, Sm, RNP, SSA, SSB were measured on the Luminex platform. Disease activity was assessed using visual analog scale (VAS) ratings defined by the International Myositis Assessment and Clinical Research (IMACS) group. Associations of gene expression with IFN gene score, disease activity measures and autoantibodies were assessed by Spearman correlation analysis.
We find a positive correlation of BAFF and DBAFF expression with disease activity measures, including the global VAS score, muscle VAS score and extraskeletal muscle VAS score. Elevated BAFF and DBAFF expression also correlate with increased IFN gene scores. Furthermore, we find IIM subjects with autoantibodies to SSA, SSB or any RNA-binding protein (SSA, SSB, RNP and Sm) have increased expression of BAFF and DBAFF. APRIL, BAFFR, TACI and BCMA expression did not correlate with disease activity measures, autoantibodies or IFN score.
|Extraskeletal muscle VAS score||r=0.32, p=0.001||r=0.47, p<0.0001|
|Muscle VAS score||r=0.25, p=0.01||r=0.35, p<0.001|
|Global VAS score||r=0.34, p<0.001||r=0.52, p<0.0001|
|IFN score||r=0.28, p=0.02||r=0.31, p<0.009|
|SSA||r=0.23, p=0.02||r=0.30, p=0.001|
|SSB||r=0.30, p=0.001||r=0.28, p=0.003|
|Any RNA binding protein||r=0.26, p=0.007||r=0.32, p<0.001|
Our findings suggest that in IIM, elevated BAFF and/or DBAFF expression may be predictive of increased disease activity, increased type 1 interferon regulated gene expression and presence of antibodies to autoantigens SSA, SSB or any RNA-binding protein. Further work is needed on the potential role of BAFF and/or DBAFF expression serving as markers of disease activity or treatment response in IIM.
To cite this abstract, please use the following information:
McNallan, Kelly T., Bilgic, Hatice, Crowson, Cynthia S., Ytterberg, Steven R., Amin, Shreyasee, Erik, Peterson J., et al; BAFF Expression Correlates with Idiopathic Inflammatory Myopathy Disease Activity Measures, Interferon Signature and Autoantibodies. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :15