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World J Rheumatol. Jul 12, 2015; 5(2): 59-68
Published online Jul 12, 2015. doi: 10.5499/wjr.v5.i2.59
Pathogenetic mechanisms of antiphospholipid antibody production in antiphospholipid syndrome
Rohan Willis, Emilio B Gonzalez
Rohan Willis, Emilio B Gonzalez, Antiphospholipid Standardization Laboratory, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555-1165, United States
Author contributions: Both authors contributed significantly to the literature review, writing of the article and final approval of the document.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest relevant to this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Emilio B Gonzalez, MD, FACP, FACR, Director and Chief, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-1165, United States.
Telephone: +1-409-9387409 Fax: +1-409-9381479
Received: June 30, 2014
Peer-review started: July 1, 2014
First decision: July 18, 2014
Revised: March 24, 2015
Accepted: April 10, 2015
Article in press: April 14, 2015
Published online: July 12, 2015

Antiphospholiipid syndrome (APS) is an autoimmune disease characterized by the pathological action of antiphospholipid antibodies (aPL), that leads to recurrent pregnancy loss and thrombosis. Despite limited evidence, it is clear that there are both inherited and acquired components of the ontogeny of these antibodies. Animal genetic studies and human familial and population studies highlight the influence of genetic factors in APS, particularly human leukocyte antigen associations. Similarly, both animal and human studies have reported the importance of acquired factors in APS development and infectious agents in particular have a great impact on aPL production. Bacterial and viral agents have been implicated in the induction of autoimmune responses by various mechanisms including molecular mimicry, cryptic autoantigens exposure and apoptosis. In this review we highlight the latest updates with regards to inherited and acquired factors leading to the manufacturing of pathogenic antibodies and APS.

Keywords: Antiphospholipid, Autoimmune, Infections, Antibody production, Susceptibility, Genetic, Human leukocyte antigen, Environmental, Immune tolerance

Core tip: This article reviews the most up to date theories regarding the production of pathogenic antiphospholipid antibodies (aPL) in antiphospholipid syndrome. It focuses on both the genetic and environmental aspects related to aPL production. The genetic factors highlighted include human leukocyte antigen (HLA) and non-HLA associations and where available, data linking genes to clinical manifestations is presented. The key infectious agents linked to the formation of pathogenic aPL and those mechanisms by which these agents induce a break in immune tolerance are also discussed.