Anti-MYC-associated zinc finger protein antibodies are associated with inflammatory atherosclerotic lesions on 18F-fluorodeoxyglucose positron emission tomography

Atherosclerosis. 2017 Apr:259:12-19. doi: 10.1016/j.atherosclerosis.2017.02.010. Epub 2017 Feb 20.

Abstract

Background and aims: Atherosclerosis is a chronic inflammatory process of vessel walls responsible for coronary, cerebrovascular and peripheral vascular disease, which together account for the majority of non-infective global deaths. Whilst great emphasis has been placed on lifestyle factors, a growing body of evidence supports an autoimmune component to atherosclerosis. This study evaluates a novel autoantibody against MYC-associated zinc finger protein (MAZ-Ab) as a potential marker of atherosclerosis. It compares MAZ-Ab to activity on whole-body positron-emission tomography/computed tomography (PET/CT) attributable to atherosclerosis.

Methods: Antibody screening using protein arrays was performed in patients with angiographically-proven ischaemic heart disease. Following MAZ-Ab detection, an ELISA for large-scale testing was developed. An a priori group of unselected patients attending for unrelated 18F-fluorodeoxyglucose (FDG) PET/CT was prospectively enrolled. Each completed a structured questionnaire under supervision and provided serum for analysis. PET/CT scans were evaluated for inflammatory arterial lesions. Whole-body arterial inflammatory burden was then correlated with ELISA optical density for MAZ-Ab.

Results: Protein array testing identified IgG anti-MAZ antibodies in 4/6 (67%) patients with ischemic heart disease, versus 0/10 controls. Significant positive correlations between MAZ-Ab and both increasing number of PET positive inflammatory atherosclerostic lesions (p = 0.023) and whole-body arterial inflammatory burden (p = 0.002) were shown. No traditional atherosclerotic risk factor correlated with MAZ-Ab.

Conclusions: A quantitative association between MAZ-Ab optical density on ELISA and the cumulative inflammatory burden of atherosclerosis on 18F-FDG PET/CT could be shown. These findings provide further evidence for an autoimmune component in atherosclerosis and suggest MAZ-Abs as a potential biomarker for atherosclerotic disease.

Keywords: (18)F-FDG-PET/CT imaging; Antibody; Atherosclerosis; MYC-associated zinc finger protein (MAZ); Serum amyloid A activating factor 1 (SAF-1).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atherosclerosis / blood
  • Atherosclerosis / diagnosis*
  • Atherosclerosis / diagnostic imaging
  • Atherosclerosis / immunology
  • Autoantibodies / blood*
  • Biomarkers / blood
  • DNA-Binding Proteins / immunology*
  • Enzyme-Linked Immunosorbent Assay*
  • Female
  • Fluorodeoxyglucose F18 / administration & dosage*
  • Humans
  • Inflammation / blood
  • Inflammation / diagnosis*
  • Inflammation / diagnostic imaging
  • Inflammation / immunology
  • Male
  • Middle Aged
  • Positron Emission Tomography Computed Tomography*
  • Predictive Value of Tests
  • Prognosis
  • Protein Array Analysis
  • Radiopharmaceuticals / administration & dosage*
  • Serologic Tests*
  • Severity of Illness Index
  • Transcription Factors / immunology*

Substances

  • Autoantibodies
  • Biomarkers
  • DNA-Binding Proteins
  • Radiopharmaceuticals
  • Transcription Factors
  • c-MYC-associated zinc finger protein
  • Fluorodeoxyglucose F18