Risk of developing antiphospholipid antibodies following viral infection: a systematic review and meta-analysis

Lupus. 2018 Apr;27(4):572-583. doi: 10.1177/0961203317731532. Epub 2017 Sep 24.


Objective The objective of this paper is to conduct a systematic review and meta-analysis on the risk of developing elevated antiphospholipid (aPL) antibodies and related thromboembolic and/or pregnancy events following a viral infection. Method We searched Medline, EMBASE, Web of Science, PubMed ePubs, and Cochrane Central Register of Controlled Trials through June 2016. Independent observational studies of elevated aPL antibodies in patients with a viral infection compared with controls or patients with lupus were included. Results We analyzed 73 publications for 60 studies. Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) were most commonly reported. Compared with healthy controls, patients with HIV were more likely to develop elevated anticardiolipin (aCL) antibodies (risk ratio (RR) 10.5, 95% confidence interval (CI) 5.6-19.4), as were those with HCV (RR 6.3, 95% CI 3.9-10.1), hepatitis B virus (HBV) (RR 4.2, 95% CI 1.8-9.5), and Epstein-Barr virus (EBV) (RR 10.9 95% CI 5.4-22.2). The only statistically significant increased risk for anti-β2-glycoprotein I (anti-β2-GPI) antibodies was observed in patients with HCV (RR 4.8 95% CI 1.0-22.3). Compared with patients with lupus, patients with HIV were more likely to develop elevated aCL antibodies (RR 1.8, 95% CI 1.3-2.6), and those with EBV, elevated anti-β2-GPI antibodies (RR 2.2, 95% CI 1.3-3.9). Thromboembolic events were most prevalent in patients with elevated aPL antibodies who had HCV (9.1%, 95% CI 3.0-18.1), and HBV (5.9%, 95% CI 2.0-11.9) infections, and pregnancy events were most prevalent in those with parvovirus B19 (16.3%, 95% CI 0.78-45.7). However, compared to virus-infected patients with negative aPL antibodies, the only statistically significant increased risk was observed in those with HCV and positive aPL. Conclusions Viral infection can increase the risk of developing elevated aPL antibodies and associated thromboembolic events. Results are contingent on the reported information.

Keywords: Antiphospholipid syndrome; anticardiolipin antibodies; infection; meta-analysis; observational studies; systematic review; thromboembolic events.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Antiphospholipid / blood*
  • Antiphospholipid Syndrome / blood
  • Antiphospholipid Syndrome / diagnosis
  • Antiphospholipid Syndrome / epidemiology*
  • Antiphospholipid Syndrome / immunology
  • Biomarkers / blood
  • Female
  • Host-Pathogen Interactions
  • Humans
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / epidemiology*
  • Lupus Erythematosus, Systemic / immunology
  • Odds Ratio
  • Pregnancy
  • Pregnancy Complications, Cardiovascular / blood
  • Pregnancy Complications, Cardiovascular / diagnosis
  • Pregnancy Complications, Cardiovascular / epidemiology*
  • Pregnancy Complications, Cardiovascular / immunology
  • Prevalence
  • Risk Assessment
  • Risk Factors
  • Thromboembolism / blood
  • Thromboembolism / diagnosis
  • Thromboembolism / epidemiology*
  • Thromboembolism / immunology
  • Virus Diseases / diagnosis
  • Virus Diseases / epidemiology*
  • Virus Diseases / virology


  • Antibodies, Antiphospholipid
  • Biomarkers