Background To date, the exact prevalence of anti-β₂ glycoprotein I domain I (anti-β₂GPI-DI) antibodies in patients with antiphospholipid syndrome (APS) and their role when assessing thrombosis risk is uncertain. Objectives To estimate the prevalence of anti-β₂GPI-DI in patients with APS and to determine whether anti-β₂GPI-DI-positive individuals are at greater risk of thrombosis, as compared with individuals without anti-β₂GPI-DI, by systematically reviewing the literature. Methods A detailed literature search was applied a priori to Ovid MEDLINE In-Process and Other Non-Indexed Citation 1986 to present and to abstracts from the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR)/Association for Rheumatology Health Professionals (ARHP ) Annual Meetings (2011–2015). Results A total of 11 studies, including 1,585 patients, were analyzed. Patients were distributed as follow: 1,218 patients APS (45.4% anti-β₂GPI-DI-positive; in more detail: 504 primary APS [55.4% anti-β₂GPI-DI-positive], 192 secondary APS [43.2% anti-β₂GPI-DI-positive], and 522 not specified), 318 with systemic lupus erythematosus (SLE; 26.7% anti-β₂GPI-DI-positive), 49 asymptomatic carriers of antiphospholipid antibodies (aPL) (30.6% anti-β₂GPI-DI-positive), and 1,859 healthy controls. When considering the five studies eligible for thrombotic risk assessment, four studies found a significant association of anti-β₂GPI-DI-positivity with thrombotic events, whereas one study found no predictive correlation with thrombosis (overall odds ratio [OR] for pooled data: 1.99; 95% confidence interval [CI]: 1.52–2.6; p < 0.0001). Conclusion We report an overall estimated median prevalence of anti-β₂GPI-DI antibodies of 44.3% in patients with APS and/or SLE and a significantly higher prevalence among patients with APS compared with SLE alone. Anti-β₂GPI-DI antibodies might represent a promising tool when assessing thrombotic risk in patients with APS. M.R. and I.C. searched the literature, assisted with the organization of the manuscript, interpreted and collected data, and wrote and edited the review. P.L.M., D.R., and S.S. interpreted and collected data, helped to design the figures and panel, and wrote and edited the review.

Recently, our group conceived a risk score for clinical manifestations of APS (the global APS score, or GAPSS) that takes into account the combination of independent cardiovascular risk factors and the aPL positivity profile. These include hyperlipidaemia, arterial hypertension, aCL, anti-β2 glycoprotein-I, aPS-PT and the LA. A complementary version, the adjusted GAPSS (aGAPSS), which excludes aPS-PT, was also designed. The aim of our study was to systematically review the literature to assess the clinical utility of the GAPSS and aGAPSS for risk stratification of any APS clinical manifestation. We pooled data from available cohort studies, including a total of 10 studies, comprising 2273 patients, in which the GAPSS has been applied. A search strategy was developed a priori to identify an available cohort that reported findings which investigated the clinical utility of GAPSS or aGAPSS. Seven studies used the GAPSS in their cohort, whereas three studies used the aGAPSS. In brief, we found a statistically significant difference in the cumulative GAPSS and aGAPSS between patients that experienced an arterial and/or venous thrombotic event [cumulative mean GAPSS (s.d.) 10.6 (4.74) and aGAPSS 7.6 (3.95)], patients without any thrombotic manifestation [cumulative GAPSS 7.01 (5.46) and aGAPSS 4.9 (4.33)] and patients with pregnancy morbidity [cumulative GAPSS 8.79 (2.59) and aGAPSS 6.7 (2.8)]. The highest levels of GAPSS were found in patients that experienced arterial thrombosis [mean GAPSS 12.2 (5.2)] and patients that experienced any recurrences of clinical manifestations of APS [mean GAPSS 13.7 (3.1)]. GAPSS may represent a useful tool to assess the thrombosis or pregnancy loss risk in aPL-positive patients, switching from the concept of aPL as a sole diagnostic antibody to aPL as risk factors for clinical events.