Clinical relevance of antiphospholipid antibodies in systemic sclerosis: A systematic review and meta-analysis

Semin Arthritis Rheum. 2017 Apr;46(5):615-624. doi: 10.1016/j.semarthrit.2016.10.004. Epub 2016 Oct 13.


Objective: To evaluate the clinical relevance of antiphospholipid antibodies (aPL) in systemic sclerosis (SSc).

Methods: A systematic search of EMBASE and PubMed databases from January 1983 to July 2016 was carried out according to PRISMA guidelines whereas Peto׳s odds ratio (OR) for rare events was used for the meta-analysis.

Results: The pooled prevalence of participants positive for IgG and IgM anticardiolipin (aCL) antibodies was higher in SSc than controls (12.8% vs 1.6% and 7.8% vs 0.6%; p < 0.0001 for both) as was that of IgG and IgM anti-beta-2-glycoprotein-I antibodies (aβ2GPI) (6.1% vs 0.58%, p < 0.0001; 3.5% vs 0.3%, p = 0.001). The pooled prevalence of pulmonary arterial hypertension (PAH) was more common in SSc positive than negative patients for aCL (IgG/IgM combined) (26.5% vs 10.9%, p < 0.0001) whereas the pooled prevalence of renal disease (RD) was more common in IgG aCL positive than negative patients (36.3% vs 10.9%, p = 0.02). The pooled prevalence of thrombosis was higher in IgG aCL, IgM aCL, and IgM aβ2GPI positive than negative SSc patients (12.6% vs 1.4%, p < 0.0001), (15.1% vs 2.7%, p = 0.002) and (15% vs 0.78%, p = 0.009), respectively. The pooled prevalence of digital infarction/ischemia (DI) was higher in IgG aCL and IgM positive than negative SSc (52.8% vs 39.8%, p = 0.002) and (68.1% vs 29%, p = 0.07).

Conclusions: A strong relationship exists between aCL and aβ2GPI of IgG/IgM isotype and SSc; patients positive for these antibodies are more likely to suffer from PAH, RD, thrombosis, and DI. However, data expressed as frequency of aPL positive patients rather than average antibody titers preclude further insight into the relevance of these assumptions.

Keywords: Anti-beta(2)glycoprotein-I; Anticardiolipin; Antiphospholipid antibodies; Lupus anticoagulant; Systemic sclerosis.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Antiphospholipid / blood*
  • Antiphospholipid Syndrome / blood*
  • Antiphospholipid Syndrome / complications
  • Antiphospholipid Syndrome / physiopathology
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Humans
  • Hypertension, Pulmonary / complications
  • Kidney Diseases / complications
  • Male
  • Scleroderma, Systemic / blood*
  • Scleroderma, Systemic / complications
  • Scleroderma, Systemic / physiopathology
  • Thrombosis / complications


  • Antibodies, Antiphospholipid
  • Biomarkers