Determination of Oxidized Low‐Density Lipoproteins (ox‐LDL) versus ox‐LDL/β2GPI Complexes for the Assessment of Autoimmune‐Mediated Atherosclerosis

Abstract

The immunolocalization of oxidized low-density lipoproteins (ox-LDL), beta2-glycoprotein I (beta(2)GPI), CD4(+)/CD8(+) immunoreactive lymphocytes, and immunoglobulins in atherosclerotic lesions strongly suggested an active participation of the immune system in atherogenesis. Oxidative stress leading to ox-LDL production is thought to play a central role in both the initiation and progression of atherosclerosis. ox-LDL is highly proinflammatory and chemotactic for macrophage/monocyte and immune cells. Enzyme-linked immunosorbent assays (ELISAs) to measure circulating ox-LDL have been developed and are being currently used to assess oxidative stress as risk factor or marker of atherosclerotic disease. ox-LDL interacts with beta(2)GPI and circulating ox-LDL/beta(2)GPI complexes have been demonstrated in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). It has been postulated that beta(2)GPI binds ox-LDL to neutralize its proinflammatory and proatherosclerotic effects. Because beta(2)GPI is ubiquitous in plasma, its interaction with ox-LDL may mask oxidized epitopes recognized by capture antibodies potentially interfering with immunoassays results. The measurement of ox-LDL/beta(2)GPI complexes may circumvent this interference representing a more physiological and accurate way of measuring ox-LDL.

Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes

“…ADMA values were dichotomized by the median value (0.68 μmol/L). Due to skewed distribution, values derived from log-transformed Onat et al Apparently "low" asymmetric dimethylarginine Anadolu Kardiyol Derg 2014; 14: [26][27][28][29][30][31][32][33] (geometric) means were used for ADMA and six other variables. For such variables, an SD value of (for example) 1.7 indicates the factor needed to multiply or divide the mean value to obtain the limits of the SD.…”

“…Subjects with "apparently" low ADMA levels may represent being both harbinger of an autoimmune process and concomitantly reflect partial escape of ADMA protein from immunoassay. In analogy, complexes of β2-glycoprotein I-Lp(a) (or oxidized LDL) have been found associated with stable (32) and acute CHD (33) wherein was pointed out that immunoassay results may be interfered due to failure by capture antibodies to recognize oxidized epitopes (33), in this instance, presumably, of ADMA. An association between serum ADMA and endothelial function was lacking also in patients with rheumatoid arthritis (34).…”

Aggregation of lipoprotein(a) to apolipoprotein A-I underlying HDL dysfunction as a major coronary risk factor

“…Indeed, elevated levels of β2-glycoprotein I-Lp(a) complexes have shown in casecontrol studies association with coronary artery disease (19,20). Immunoassay results may be interfered due to failure by capture antibodies to recognize oxidized epitopes interacting with β2-GPI (20)…”

Antiphospholipid Antibodies and Their Association with Atherosclerotic Changes in Patients with Systemic Lupus Erythematosus – Review of Literature and Own Experiences

“…In vitro investigations showed enhanced macrophage uptake of IgG immune complexes with oxLDL/β2-GPI. Measurement of oxLDL/β2-GPI complexes may represent a more physiological, clinically relevant, and accurate way of assessing oxidative stress and atherogenesis (Lopez et al, 2007).…”

“…The prolonged persistence of oxLDL/β2-GPI complexes can stimulate immune mechanisms and antibody production (aoxLDL/β2-GPI) that contribute to atherosclerosis (Lopez et al, 2007). The study performed in patients with selected systemic connective tissue diseases including SLE and APS showed aoxLDL/β2-GPI IgG significantly increased in SLE patients.…”