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Abstract Number: 658

Up-Regulation of A Disintegrin and Metalloprotease with Thrombospondin Type I Repeats-13 Correlates with Ischemic Cerebrovascular Disease in Systemic Lupus Erythematosus Patients

Consuelo Lopez de Padilla1, Molly Hein2, Cynthia S. Crowson3, Christopher Choo4, Abigail B. Green3, Michelle Petri5, Hatice Bilgic6, Emily Baechler Gillespie6 and Ann M. Reed7, 1Rheumatology/Immunology Research, Mayo Clinic, Rochester, MN, 2Mayo Clinic, Rochester, MN, 3Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 4Division of Rheumatology, Mayo Clinic, Rochester, MN, 5Johns Hopkins University School of Medicine, Baltimore, MD, 6University of Minnesota Medical School, Minneapolis, MN, 7Rheumatology, Mayo Clinic, Rochester, MN

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Biomarkers, cerebrovascular disease and systemic lupus erythematosus (SLE)

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Session Information

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose: ADAMTS13 (A Disintegrin-like And Metalloprotease with ThromboSpondin type 1 motif) belongs to a recently described group of metalloproteinase enzymes which possess proteoglycanase and anti-angiogenic activities.  ADAMTS13 limits platelet thrombogenesis through the cleavage of von Willebrand factor (vWF) and has been implicated in the pathogenesis of thrombotic thrombocytopenic purpura (TTP), a potentially fatal complication of systemic lupus erythematosus (SLE) and other rheumatic diseases. The pathogenic role of ADAMTS13 in TTP associated to SLE has been investigated; however, although TTP and SLE may have overlapping clinical features, they are distinct entities. We investigated ADAMTS13 messenger RNA (mRNA) levels as a biomarker of disease features in SLE.

Methods:  Here, we measured and compared mRNA levels of ADAMTS13 in peripheral blood cells in 309 SLE and 23 healthy subjects by whole-genome microarray using the Illumina Bead Array Platform. We examined correlations of ADAMTS13 mRNA expression levels with clinical features, laboratory parameters and disease activity (systemic lupus erythematosus disease activity index; SLEDAI). Comparisons of mRNA levels and their association with distinct clinical characteristics were assessed using the rank sum test and Spearman rank correlation analysis.

Results:  The results showed that the median of ADAMTS13 mRNA expression levels were significantly increased in blood cells of SLE patients (median, 121.3 [25th, 75th quartile, 116.8, 126.4] compared to healthy controls (median, 119.1 [25th, 75th quartile, 114.8, 121.3] (p=0.028).  No significant differences were found between ADAMTS13 mRNA levels and symptoms associated with the ACR criteria for classification of SLE. Notably, mRNA copy number levels of ADAMTS13 were significantly increased in SLE patients with a history of stroke (n= 11 ) (median, 126.5, [25th, 75th quartile, 121.3, 129.2]) or Transient Ischemic Attack (TIA) (n= 5) (median, 126.6, [25th, 75th quartile, 126.3, 137.8]) compared to those without stroke or TIA (median, 121.0, [25th, 75th quartile, 116.6, 126.3]; (median, 121.6, [25th, 75th quartile, 116.6, 127.4], respectively) (p=0.015; p=0.024; respectively). We next sought to compare the mRNA ADAMTS13 levels in the 26 of 309 SLE patients with coronary artery disease (CAD). No significant differences were observed between ADAMTS13 mRNA levels in SLE patients with CAD compared to patients without CAD (p=0.35). Similarly, ADAMTS13 expression was not found to be correlated with SLE disease activity.

Conclusion:  These results indicate that increased expression of ADAMTS13 mRNA in blood cells is associated with presence of ischemic cerebrovascular disease (stroke and TIA) in SLE patients and suggests a potential role for ADAMTS13 in the pathogenesis of ischemic cerebrovascular disease in SLE patients.


Disclosure:

C. Lopez de Padilla,
None;

M. Hein,
None;

C. S. Crowson,
None;

C. Choo,
None;

A. B. Green,
None;

M. Petri,
None;

H. Bilgic,
None;

E. Baechler Gillespie,
None;

A. M. Reed,
None.

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