Detection of anti-non bilayer phospholipids arragements antibodies and genotyping in patients with systemic lupus erythematosus and secondary antiphospholipid syndrome

Phospholipids are the main structural constituents of all cell membranes, their form the smooth bilayer matrix that delimited cells in which membrane proteins are located. However, some anionic phospholipids can lead to the formation of nonbilayer phospholipid arrangements (NPA) within the bilayer. NPA are transient but when they are stabilized by the drugs chlorpromazine, procainamide or hydralazine, which produced lupus-like disease in humans, they induce a disease resembling human lupus in mice. Mice present IgM and IgG antibodies against NPA which appear 4 weeks before that autoantibodies against cardiolipin, histones, nuclear and lupus anticoagulant antibodies. Mice also present histopathological abnormalities in the skin and kidneys similar to those observed in systemic lupus erythematosus (SLE). We proposed that the recognition of NPA by anti-NPA antibodies and after by the classical complement pathway causes cell lysis exposing intracellular antigens with the consequent formation of autoantibodies. Antibodies against NPA have been described in patients with SLE, lepromatous leprosy and hypertensive disorders of pregnancy. The present investigation is a clinical study not randomized, prospective, in Mexican mestizos patients of any sex and age, with SLE or with secondary antiphospholipid syndrome in which we found that the elevated levels of anti-NPA antibodies could trigger autoimmunity in these diseases and we determined that high titers lead to increased activity and correlate with the expression of HLA-DR, HLA-DQ, HLA-A, HLA-B, IL-10 (-1082G/A, -819C/T, -592C/A) and PTPN22 (+1858C/T) alleles. All clinic assays were approved by the Committee of Bioethics of our Institutions.