Article

Dendritic cells: An important link between antiphospholipid antibodies, endothelial dysfunction, and atherosclerosis in autoimmune and non-autoimmune diseases

Division of Rheumatology, Albert Einstein College of Medicine/Montefiore Medical Center, F 701N, 1300 Morris Park Ave, Bronx, NY 10461, USA. Electronic address: .
Clinical Immunology (Impact Factor: 3.99). 12/2012; 146(3):197-206. DOI: 10.1016/j.clim.2012.12.002
Source: PubMed

ABSTRACT The presence of dendritic cells, antigen-presenting cells that link innate and adaptive immunity, is necessary to generate and maintain the production of antiphospholipid antibodies in response to exposed intracellular phospholipids on the outer surface of apoptotic cells. In turn, antiphospholipid antibodies enhance dendritic cell-induced inflammatory and proatherogenic responses in a number of conditions that are associated with accelerated atherosclerosis, including diabetes, chronic kidney disease, periodontal infections, and aging. While altering dendritic cells by modifying the ubiquitin-proteasome system enhances antiphospholipid antibody production and leads to development of accelerated atherosclerosis and autoimmune features, inducing tolerance by dendritic cell manipulation leads to decreased atherosclerosis and thrombosis. Therefore, further translational studies are needed to understand the interplay between dendritic cells and antiphospholipid antibodies, and to develop potential new therapies for antiphospholipid syndrome and atherosclerosis. Here we review current experimental and translational studies that have examined the role of dendritic cells in antiphospholipid antibody formation and in antiphospholipid-associated atherosclerosis and thrombosis.

1 Follower
 · 
77 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Our aim is to investigate a possible association of circulating anti-beta2-glycoprotein I antibodies (ABGPI) with the endothelial dysfunction, nitric oxide bioactivity dysregulation, and the inflammatory status that surrounds peripheral arterial disease. We carried out an observational translational study, including 50 male patients with intermittent claudication and a healthy control group of 10 male subjects, age and sex matched with the cases. Flow-mediated arterial dilatation (FMAD) was assessed as a surrogate of endothelial dysfunction, and C-reactive protein (hsCRP) was determined as a marker of inflammation. Nitrite plasma levels were measured by colorimetric analysis. Circulating ABGPI titer was detected with indirect immunofluorescence. Titers <1 : 10 represented the reference range and the lower detection limit of the test. Circulating ABGPI titer ≥1 : 10 was detected in 21 (42%) patients and in none of the control subjects (P < 0.01). Patients with ABGPI titer ≥1 : 10 had a lower FMAD (P = 0.01). The CRP levels were higher in patients with ABGPI titer ≥1 : 10 (P = 0.04). The nitrite plasma levels were higher in patients with ABGPI titer ≥1 : 10 (P < 0.01). These data suggest that these circulating ABGPI may collaborate in the development of atherosclerosis; however, further prospective studies are required to establish a causal relationship.
    10/2013; 2013:268079. DOI:10.1155/2013/268079
  • [Show abstract] [Hide abstract]
    ABSTRACT: Celiac disease is a life-long autoimmune disease affecting multiple organs of genetically susceptible individuals. One of the extra intestinal manifestations of the disease is thromboembolic events like strokes, veins' thrombosis, and pregnancy losses. Hypercoagulable autoimmune diseases like lupus erythematosus and antiphospholipid syndrome, associated with celiac disease just add risk to the patients. Pathogenic predisposing avenues increasing the hypercoagulability in celiac disease are multiple: nutritional deficiencies (B12, folate, and vitamin K), genetic predisposition (MTHFR mutations), thrombophilic autoantibodies, hyperhomocysinemia, endothelial dysfunction and platelet abnormalities. Primary pharmacologic thromboprophylaxis or treating the predisposing factors should be considered on a personal basis.
    Autoimmunity Reviews 11/2014; DOI:10.1016/j.autrev.2014.07.004 · 7.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Circulating anti-β2-glycoprotein I (ABGPI) antibodies are associated with peripheral arterial disease (PAD) and induce the expression of leukocyte adhesion molecules and proinflammatory cytokines by endothelial cells. Our aim is to study a transcriptional activation pathway of the innate immune system through the cellular signalling cascade triggered by receptors Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) of endothelial cells after the exposure of these cells to seropositive ABGPI human serum obtained from PAD patients. We obtained serum samples from PAD patients and controls without PAD. ABGPI serum titer was detected using indirect immunofluorescence. Our sample was stratified into three groups: group I (PAD and ABGPI titer ≥1:100; n = 15), group II (PAD and ABGPI titer <1:100; n = 15), and control participants (no PAD; n = 15). All serum samples were incubated with human aortic endothelial cell (HAEC) culture. Genomic expression of TLR2 and TLR4 receptors and their shared intracellular signalling molecules, myeloid differentiation primary response gene 88 (MyD88), and interleukin (IL)-1 receptor-associated kinase (1IRAK1), were measured after the exposure of HAECs to each serum. HAEC genomic expression of TLR4 was higher after the exposure to group I serum than after the exposure to group II serum (log10×10-relative quantification [RQ]: 1.80 ± 0.42 vs 1.37 ± 0.39; P = .01) or control serum (log10×10-RQ: 1.80 ± 0.42 vs 1.09 ± 0.26; P < .01). TLR4 expression was higher in group II than in the control group (log10×10-RQ: 1.37 ± 0.39 vs 1.09 ± 0.26; P = .04). TLR4 expression correlated with MyD88 (r = 0.54; P < .01) and IRAK1 (r = 0.55; P < .01) expression. We recorded a positive correlation between MyD88 and IRAK1 genomic expression (r = 0.58; P < .01). Our results suggest that serum from PAD patients with elevated ABGPI antibodies induces a genomic overexpression of TLR4 and its cellular signalling molecules in endothelial cells.
    Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 01/2014; DOI:10.1016/j.jvs.2013.11.066 · 2.98 Impact Factor