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.


Elevated Cytokines and Chemokine Levels in Antiphospholipid Antibody (aPL)-Positive Patients.

L. Murthy,  Vijaya, Jatwani,  Shraddha, A. Aguilar-Valenzuela,  Renan, D. Doan,  Ellis, Papalardo,  Elizabeth, B. Gonzalez,  Emilio, S. Pierangeli,  Silvia

Background:

Based on in vitro and animal studies, certain cytokines and chemokines such as tissue factor (TF), vascular endothelial growth factor (VEGF), soluble (s) E-selectin (sE-sel), and tumor necrosis factor (TNF)-a have been shown to be associated with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Here we examined the levels of cytokines/chemokines in aPL-positive patients with or without SLE, and compared them to controls.

Methods:

Baseline sera/plasma of persistently aPL-positive patients [IgG/M Anticardiolipin antibody (aCL) > 40U, IgG/M anti-b2 glycoprotein-I antibody (ab2GPI) > 20U, and/or positive lupus anticoagulant test] were obtained from an ongoing pilot interventional clinical study (clinical trials. gov #: NCT00674297). The biomarker levels of these 22 aPL-positive patients (primary APS: 8, APS with SLE: 8, asymptomatic aPL without SLE: 4 and asymptomatic aPL with SLE: 2) were compared to 22 matched healthy controls with no evidence of autoimmune, infectious, or inflammatory diseases. Interleukin (IL)-1b, IL6, IL8, TNF-a, VEGF, interferon inducible protein (IP)-10 and sCD40L were measured in serum using a Multiplex Assay (Millipore Milliplex™); titers of sE-sel, and sTF were detected by ELISA. The Kruskal-Wallis test was used to compare the levels of biomarkers in aPL-positive subjects as compared to the controls. Spearman test was used to correlate the levels of the biomarkers in the different subgroups of patients.

Results:

As compared to controls, we found an increase in the levels of IL-1b, IL6, TNF- a, IP-10, sCD40L and sTF in patients with APS. In a subgroup analysis, patients with aPL/APS and SLE (n=10) had significantly higher levels of TNF-a, IP10 and sCD40L as compared to aPL/APS patients without SLE (n=12) (p= 0.05, 0.029 and 0.05, respectively).

Biomarker# Of aPL (+) samples elevated above cut-off points/(%)Means of aPL positive samplesMeans of controlsp
IL1b16/22 (73)7.650.35<0.0001
IL617/22 (77)42.150.71<0.0001
IL89/22 (41)27.4440.870.1763
TNF-a22/22 (100)14.710.46<0.0001
VEGF12/22 (54)208.78113.590.9778
IP-1022/22 (100)683.43106.7<0.0001
sCD40L21/22 (95)1070.1924.67<0.0001
s TF16/16 (100)449.5913.05<0.0001
sE-sel3/16 (19)20.7842.040.0006

Conclusions:

Our results underscore the importance of biomarkers in aPL-positive patients. This may help better understand the pathogenic mechanisms involved, and the development of targeted treatments.

To cite this abstract, please use the following information:
L. Murthy, Vijaya, Jatwani, Shraddha, A. Aguilar-Valenzuela, Renan, D. Doan, Ellis, Papalardo, Elizabeth, B. Gonzalez, Emilio, et al; Elevated Cytokines and Chemokine Levels in Antiphospholipid Antibody (aPL)-Positive Patients. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2253
DOI: 10.1002/art.30016

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