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.


Atherosclerosis Biomarkers in Systemic SclerosisA Multiplex Analysis.

Khanna1,  Dinesh, Divekar2,  Anagha A., Singh2,  Ram Raj, Kaplan1,  Mariana J., McMahon3,  Maureen A., Furst2,  Daniel E., Ragavendra3,  Nagesh

University of Michigan, Ann Arbor, MI
UCLA Medical School, Los Angeles, CA
UCLA David Geffen School of Medicine, Los Angeles, CA

Background/Purpose:

Increasing evidence suggests that atherosclerosis is increased in systemic sclerosis (SSc) compared to healthy individuals. However, the pathogenesis of atherosclerosis in SSc remains unknown. This study aimed to identify markers of fibrosis, vasculopathy, and inflammation that may be involved in the pathogenesis of atherosclerosis in a female SSc cohort.

Methods:

The multiplex antibody array, based upon enzyme-linked immunosorbent assay (ELISA) technology, can measure multiple proteins simultaneously within a single sample. We utilized a microplate-based multiplex platform (Aushon Biosystems SearchLight) to identify 100 proteins in plasma samples from females with SSc with no history of atherosclerosis (N=46). In addition, circulating type I Interferon (IFN) activity was quantified by exposing epithelial cells to SSc serum and quantifying IFN-inducible genes by real-time PCR. All subjects underwent bilateral carotid ultrasounds to quantify plaque and intima-medial thickness (IMT) and were read by a single reader (NR). Statistical analysis was performed using Wilcoxin rank-sum test and Spearman's correlation. Significance was determined at P<0.05; no statistical adjustment was performed for multiple-testing as this analysis was hypothesis generating.

Results:

Mean age (+/- SD) of the subjects was 48.6 (+/- 13.3) years. Carotid plaque was detected in 21 (46%) of the SSc subjects. Multiplex analysis detected significant associations between biomarkers of inflammation, vasculopathy, and fibrosis with atherosclerosis in the SSc subjects. IL-2, IL-6, CRP, KGF, ICAM-1, endoglin, PAI-1, and IGFBP3 were associated with carotid plaque (P<0.05, Table 1). MPIF1, A-SAA, thrombomodulin, NTpBNP, and CC16 were correlated with carotid IMT (P<0.5, Table 2). Type I IFN signatures were not associated with plaque or CIMT in SSc.

Table 1. Proteins associated with carotid plaque in SSc

 BIOMARKER (pg/ml)NO PLAQUE, mean(SD)PLAQUE, mean(SD)P-value
InflammationIL-23.0 (2.6)5.0 (3.8)0.03
 IL-611.0 (13.5)25.2 (48.5)0.05
 CRP1627772 (2437838.6)3856899.5 (4734651.2)0.01
VasculopathyKGF0.8 (2.1)1.6 (2.1)0.02
 ICAM-1403423.3 (131159.9)539301.8 (242768.3)0.04
 Endoglin22444.1 (9253)28156.3 (8860.8)0.04
FibrosisPAI-19607.8 (6527.1)6680 (5898)0.05
 IGFBP3404848.8 (116838.8)322117.3 (93709)0.01

Table 2. Correlation of proteins with carotid IMT in SSc

 BIOMARKERIMT (r)P-value
InflammationMPIF-10.310.04
 A-SAA0.310.04
VasculopathyThrombomodulin0.320.04
 NTpBNP0.420.01
FibrosisCC160.370.01

Conclusion:

Distinct biomarkers of inflammation, vasculopathy, and fibrosis are associated with carotid plaque and IMT in SSc. Factors associated with carotid IMT differ from those associated with plaque in SSc. Further studies are needed to confirm the validity of these associations in another SSc cohort and their putative role as biomarkers of vascular events in this disease.

To cite this abstract, please use the following information:
Khanna, Dinesh, Divekar, Anagha A., Singh, Ram Raj, Kaplan, Mariana J., McMahon, Maureen A., Furst, Daniel E., et al; Atherosclerosis Biomarkers in Systemic SclerosisA Multiplex Analysis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1493
DOI:

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