Login

Journal Image
Current Molecular Medicine
ISSN (Print): 1566-5240
ISSN (Online): 1875-5666
VOLUME: 11
ISSUE: 9
DOI: 10.2174/156652411798062377      Price:  $58









Oxidized Human Beta2-Glycoprotein I: Its Impact on Innate Immune Cells

img
Author(s): B. Buttari, E. Profumo, A. Capozzi, M. Sorice and R. Rigano
Pages 719-725 (7)
Abstract:
Beta2-glycoprotein I (β2-GPI), an abundant 50 kDa plasma glycoprotein, is the most common target for antiphospholipid antibodies (aPLs). These autoantibodies are associated with thrombotic events in patients with anti-phospholipid antibody syndrome (APS) and systemic lupus erythematosus (SLE) and are proatherogenic. β2-GPI can also stimulate a vigorous adaptive cellular immune response in these patients. Although much is known about β2-GPI as a cofactor in autoimmune diseases, crucial information is still lacking to clarify why this abundant self plasma protein is the target of autoimmune responses. Throughout the years, a remarkable number of theories have been proposed to explain how the immune system recognises self. On the basis of a large variety of epidemiological, clinical and experimental evidence, it has been suggested that an unfortunate interplay of genetic susceptibility and environmental factors may play an important role in generating an abnormal immune response. Among the environmental factors, oxidative stress is one of the major events causing protein structural modifications, thus inducing the appearance of neo/cryptic epitopes of β2-GPI able to activate the immune system. In particular, oxidized β2-GPI is able to induce phenotypic and functional maturation of dendritic cells which represent the link between innate and adaptive immunity. Chronic activation of autoimmune reactions against this self protein modified by oxidative events may contribute to local and systemic inflammation, thus sustaining endothelial dysfunction in patients with APS, SLE and cardiovascular diseases. The role of oxidative stress in β2-GPI-mediated immune response is described in the light of our research experience and of relevant literature emerging in the field.
Keywords:
Autoimmunity, beta2-glycoprotein I, dendritic cells, endothelial dysfunction, innate immunity, monocytes, oxidative stress, apolipoprotein, coagulation system, vascular biology, homeostasis, anti-phospholipid antibody syndrome, systemic lupus erythematosus, atherosclerosis, antiphospholipid antibodies
Affiliation:
Istituto Superiore di Sanita, Department of Infectious, Parasitic and Immune-mediated Diseases, 299 Viale Regina Elena, Rome, Italy.