AUTHOR=Virella Gabriel , Lopes-Virella Maria F. TITLE=The Pathogenic Role of the Adaptive Immune Response to Modified LDL in Diabetes JOURNAL=Frontiers in Endocrinology VOLUME=3 YEAR=2012 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2012.00076 DOI=10.3389/fendo.2012.00076 ISSN=1664-2392 ABSTRACT=
The main causes of morbidity and mortality in diabetes are macro and microvascular complications, including atherosclerosis, nephropathy, and retinopathy. As the definition of atherosclerosis as a chronic inflammatory disease became widely accepted, it became important to define the triggers of vascular inflammation. Oxidative and other modifications of lipids and lipoproteins emerged as major pathogenic factors in atherosclerosis. Modified forms of LDL (mLDL) are pro-inflammatory by themselves, but, in addition, mLDLs including oxidized, malondialdehyde (MDA)-modified, and advanced glycation end (AGE)-product-modified LDL induce autoimmune responses in humans. The autoimmune response involves T cells in the arterial wall and synthesis of IgG antibodies. The IgG auto-antibodies that react with mLDLs generate immune complexes (IC) both intra and extravascularly, and those IC activate the complement system as well as phagocytic cells via the ligation of Fcγ receptors.