Autoantibody to apolipoprotein A-1 in hepatitis C virus infection: a role in atherosclerosis?

Abstract

Background/purpose One to three per cent of the world's population has hepatitis C virus (HCV) infection, which is not only a major cause of liver disease and cancer but also associated with an increased risk of atherosclerosis, despite an ostensibly favourable lipid profile. Autoantibodies are frequent in HCV infection and emerging evidence shows that autoantibodies could be valuable for cardiovascular disease (CVD) risk stratification. This study investigated a novel independent biomarker of CVD, autoantibodies to apolipoprotein A-1 (anti-apoA-1 IgG) and lipids in patients with chronic HCV before, during and after direct-acting anti-viral (DAA) therapy. Methods Eighty-nine blinded serum samples from 27 patients with advanced chronic HCV were assayed for lipids and anti-apoA-1 IgG by ELISA. Results Pre-treatment HCV viral load correlated with high-density lipoprotein cholesterol (HDL-C, r = 0.417; p = 0.042) and negatively with apolipoprotein (apo)B (r =-0.497; p = 0.013) and markers of CVD risk, the apoB/apoA-1 ratio (r =-0.490; p = 0.015) and triglyceride level (TG)/HDL-C ratio (r =-0.450; p = 0.031). Fourteen (52%) of 27 patients had detectable anti-apoA-1 IgG autoantibodies pre-treatment; only two became undetectable with virological cure. Autoantibody-positive sera had lower apoA-1 (p = 0.012), HDL-C (p = 0.009) and total cholesterol (p = 0.006) levels. Conclusions This is the first report of the presence of an emerging biomarker for atherosclerosis, anti-apoA-1 IgG, in some patients with HCV infection. It may be induced by apoA-1 on the surface of HCV lipoviral particles. The autoantibodies inversely correlate with apoA-1 and HDL levels and may render HDL dysfunctional. Whether these hypothesis-generating findings have clinical implications in HCV patients requires further study.

SARS-CoV2- infection as a trigger of humoral response against apolipoprotein A-1

“…First of all, these results extend the coverage of virus-mediated anti-apoA-1 IgG induction to SARS-CoV-2, as previously shown for HCV and HIV (26, 27). The inverse associations reported here between anti-apoA-1 IgGs and HDL levels are similar to what has been observed in HCV (26), and are reminiscent of the concept that HCV could hijack the scavenger receptor B-1 (SR-B1)-mediated HDL uptake to infect hepatocytes (26, 43) which has recently been transposed to SARS-CoV-2 by the recent demonstration of Wei and colleagues who identified SR-B1 as an additional receptor facilitating the SARS-CoV-2 entry into cells (44). SR-B1 being the canonical apoA-1/HDL receptor involved in reverse cholesterol efflux and HDL maturation, our results suggest that the molecular mimicry-based anti-apoA-1 IgG response in COVID-19 may concur with other established inflammatory factors to explain the low HDL and apoA-1 levels reported previously in COVID-19 (45, 46).…”

“…To assess the degree of cross reactivity between anti-SARS-CoV-2, anti-apoA-1 IgG (and control IgG) with their respective antigens, delipidated apoA-1 (purified from plasma of healthy blood donors), Spike protein was kindly provided by the institute of technology EPFL (Lausanne, Switzerland), and the two mimic peptides were coated on Maxisorp plates (NuncTM, Roskilde, Denmark) according to the anti-apoA-1 IgG protocol (17, 21–26). Commercial polyclonal anti-apoA-1 IgG (Academy Biomedical Company, Houston, TX, USA, ref: 11A-G2) and polyclonal anti-Spike IgG (Thermo Fisher Scientific, Waltham, MA, USA, ref: PA5-81795) with their respective control antibodies: goat IgG (Meridian Life Science, Memphis, TN, USA, ref: A66200H) or rabbit IgG (Dako, Santa Clara, CA, USA, ref: X0903), were added to the coated plate at increasing concentrations (1 to 10 µg/ml) for 1 h. Anti-goat or anti-rabbit alkaline phosphatase-conjugated antibodies (Sigma-Aldrich Chemie GmbH, Buchs, SG, Switzerland, refs: A-7650, A-7539) were added to detect the primary antibody binding.…”

“…TLR2 engagement and subsequent activation have been shown to be required for autoantibodies against apoA-1 (anti-apoA-1 IgG) to mediate their pro-atherogenic effects (17–20). Because anti-apoA-1 IgGs were shown to represent an independent cardiovascular (CV) risk factor associated with poor prognosis (21–25), to be elevated after viral infections (26, 27), and to be preferentially oriented against the c-ter part of apoA-1 (28, 29), we hypothesized that SARS-CoV-2 infection could elicit an anti-apoA-1 IgG response with substantial overlap with anti-SARS-CoV-2 IgG serology.…”

SARS‐CoV‐2 infection as a trigger of humoral response against apolipoprotein A‐1

“…TLR2 engagement and subsequent activation have been shown to be required for autoantibodies against apoA‐1 (anti‐apoA‐1 IgG) to mediate their pro‐atherogenic effects. 17 , 18 , 19 , 20 Because anti‐apoA‐1 IgGs were shown to represent an independent cardiovascular (CV) risk factor associated with poor prognosis, 21 , 22 , 23 , 24 , 25 , 26 to be elevated after certain viral infections, 27 , 28 and to be preferentially oriented against the c‐ter part of apoA‐1, 29 , 30 we hypothesized that SARS‐CoV‐2 infection could elicit an anti‐apoA‐1 IgG response with substantial overlap with anti‐SARS‐CoV‐2 IgG serology.…”

Seeking markers to distinguish HCV-Infected-autoimmune subjects from uninfected-autoimmune patients

“…Both HCV persistence [30,31] and IFN-α therapy [32] trigger autoimmune reactions resulting in production of auto-antibodies such as ANA, [33] AMA, ASMA and AGPCA [34,7]. In the present study the most reactive autoantibody among Egyptian HCVinfected patients was the ASMA with a recorded prevalence of 69.44% and approximately similar results were obtained by Clifford et al [35] while, others reported that its reactivity ranged between 12-66% based on technical reasons and\or differences in the populations investigated [36].…”