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 Involvement of CD36 in the Monocyte Activation by Antiphospholipid Antibodies.
Kato1, Masaru, Atsumi2, Tatsuya, Oku3, Kenji, Amengual3, Olga, Fujieda3, Yuichiro, Otomo3, Kotaro, Horita3, Tetsuya
Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Department of Medicine II, Hokkaido University Graduate School of Medicine
CD36, known as a scavenger receptor, is a transmembrane glycoprotein expressed on monocytes, macrophages, platelets and capillary endothelial cells. CD36 recognizes multiple ligands, including phosphatidylserine, and is a mediator of both atherogenesis and thrombosis. However, little data are available regarding the correlation between CD36 and thrombotic diseases. The purpose of this study is to investigate the possible involvement of CD36 in the pathophysiology of thrombosis in patients with antiphospholipid syndrome (APS).
This study comprised two sets of experiments. Firstly, a genomic polymorphism of CD36 was explored. Rs3765187, a single nucleotide polymorphism (SNP) linked to CD36 deficiency, was investigated by TaqMan PCR genotyping method in 795 Japanese, including 108 patients with APS, 265 with systemic lupus erythematosus (SLE) in the absence of APS, and 422 healthy subjects. In the second part of this study, the involvement of CD36 in antiphospholipid antibody (aPL)-induced tissue factor (TF) expression was examined using CD36 deficient mice or anti-CD36 antibody with the CD36 signal blocking property (FA6152). Purified IgG from APS patients either anticardiolipin antibodies or phosphatidylserine dependent antiprothrombin antibodies positive (Pt-aCL and Pt-aPS/PT, respectively) and monoclonal aPS/PT (231D) were used in the experiments. The aPL-induced TF expression was tested by real-time PCR method on peritoneal macrophages from CD36 deficient mice or human peripheral blood mononuclear cells (PBMC) from healthy donors pretreated with FA6152.
The minor allele frequency of rs3765187 was less frequent in APS patients (2.8% p = 0.024), but not in SLE patients (7.9% p = 0.32), compared with healthy subjects (10.2%). Pt-aCL, Pt-aPS/PT and 231D-induced TF mRNA expressions were not completely but significantly suppressed in peritoneal macrophage from CD36 deficient mice compared to wild type mice (WT).
FA6152 dose-dependently inhibited Pt-aCL, Pt-aPS/PT and 231D-induced TF mRNA expressions in human PBMC from healthy donors.
The SNP linked to CD 36 deficiency was less frequent in APS patients, suggesting that CD36 insufficiency is protective for developing APS. The deficient or suppressed CD36 function significantly reduced aPL-induced TF expression in vitro. Taken together, scavenger receptor function may be involved in the thrombotic pathophysiology in APS patients. CD36 is a new potential therapeutic target of the affected patients.
To cite this abstract, please use the following information:
Kato, Masaru, Atsumi, Tatsuya, Oku, Kenji, Amengual, Olga, Fujieda, Yuichiro, Otomo, Kotaro, et al; The Involvement of CD36 in the Monocyte Activation by Antiphospholipid Antibodies. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2254