Autoantibodies directed against phospholipids or human β₂‐glycoprotein 1 in HIV‐seropositive patients: relationship with endothelial activation and antimalonic dialdehyde antibodies

Abstract

BackgroundWe investigated the possible role of antiphospholipid (APA) and anti-human 2 -glycoprotein I (b 2 -GPI) antibodies (Ab) in thrombosis and atherosclerosis in human immunodeficiency (HIV)-positive patients, in whom they seem to be more frequent. MethodsWe measured APA and anti-b 2 -GPI Ab in 58 HIV-positive patients together with markers of disease progression, circulating b 2 -GPI, plasma lipids, biological markers of endothelial activation and integrity (plasma thrombomodulin, von Willebrand factor, vascular cell adhesion molecule 1) and with antimalonic dialdehyde antibodies (anti-MDA Ab). ResultsWe found a 41% frequency of IgG APA in the HIV-positive patients. APA IgMs were rarely positive (7%), and anti-b 2 -GPI IgGs were positive in 3·4% patients. There was no correlation between APA or anti-b 2 -GPI Ab and the presence of opportunistic infections. Although plasma thrombomodulin, von Willebrand factor and vascular cell adhesion molecule 1 were significantly increased in the HIV-positive patients, APA was correlated only with vascular cell adhesion molecule 1, suggesting that APAs are correlated with endothelial activation but not with vascular endothelial lesions. A correlation between APA and anti-MDA IgG was demonstrated using multivariate analysis (r ¼ 0·542, P < 0·0001), suggesting a relationship between the targets of these antibodies. Finally, IgG APAs are frequent in HIV infection but are not correlated with biological markers of endothelial injury. ConclusionOur results do not support a role for APA or anti-b 2 -GPI in HIV-associated silent vascular endothelial damage. However, the role of these autoantibodies in clinically relevant thrombotic events should be investigated in HIV-positive patients.

Alterations of self-reactive antibody repertoires in HIV disease: An insight into the role of T cells in the selection of autoreactive B cells

“…HLA molecules, CD95, phospholipids, human ␤2 glycoprotein-1, neutrophil cytoplasmic antigens, are frequently observed in untreated HIV-infected individuals [3][4][5][6][7][8][9]. Disturbances in mechanisms of self-recognition were shown to parallel the progression of HIV-1 infection [3,23].…”

“…Alterations of the B cell compartment include polyclonal B cell activation [1,2] and high levels of self-reactive antibodies in serum [3][4][5][6][7][8][9]. Natural antibodies of the IgM, IgG, and IgA isotype that are reactive with a stages of HIV infection using quantitative immunoblotting followed by multiparametric statistical analysis of the data.…”

Antiphospholipid antibodies induced in mice by immunization with a cytomegalovirus‐derived peptide cause thrombosis and activation of endothelial cells in vivo

“…It has been demonstrated that aPL can be induced in patients infected with many bacteria, other microorganisms (35)(36)(37)(38)(39)(40)(41)(42)(43)(44), and viruses, including CMV (45), varicella zoster virus (46), human immunodeficiency virus (47), hepatitis C (48), and Epstein-Barr virus (49). In addition, transient LAC activity in patients with Epstein-Barr virus infections has been reported (49).…”

A peptide that shares similarity with bacterial antigens reverses thrombogenic properties of antiphospholipid antibodies in vivo

“…In most cases, the presence of these antibodies was not associated with clinical manifestations of APS, and the antibodies did not require 2 GPI for binding to CL. Recently, the belief that infection-associated aPl are 2 GPI-independent, do not bind to 2 GPI in the absence of phospholipids, and are not associated with thrombosis or other clinical complications of APS has been challenged in a significant number of reports [44][45][46][47][48][49][50][51][52][53]. In one study, aCL present in leprosy patients were shown to be heterogenous with respect to their 2 GPI requirement: in 10 of 31 leprosy sera, the aCL were 2 GPI dependent, and 21 of 31 did not require 2 GPI for binding to CL.…”