Behçet's disease (BD) is a multifactorial systemic inflammatory disease of unknown aetiology characterised by several clinical manifestations including vascular involvements (i.e., both arterial and venous thrombosis). Antiphospholipid antibodies (aPLs)-including anticardiolipin (aCL), anti-β2-glycoprotein I (β2-GPI) antibodies and lupus anticoagulant (LA) are detected in systemic autoimmune diseases which contribute to thrombosis. The aim of this systematic review and meta-analysis was to evaluate the prevalence of aPLs in patients with BD as compared to controls. A protocol was registered in PROSPERO (Registration No. CRD42018088125) and a systematic literature search was conducted through PubMed, Web of Science, Embase, Scopus and ScienceDirect databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects model. Quality assessment was carried out by using the modified 9-star Newcastle-Ottawa Scale (NOS). Publication bias was evaluated via visualisation of contour- enhanced and trim and fill funnel plots along with Begg's and Egger's tests. We included ten case-control studies (a total of 999 participants from 380 BD patients and 619 controls) based on the inclusion criteria. The prevalence of aCL (OR: 12.10, 95% CI: 5.15-28.41, p<0.00001) and anti-β2-GPI antibodies (OR: 23.57, 95% CI: 1.31-423.63, p = 0.03) were statistically significant, however, the prevalence of LA was not significant (OR: 13.77, 95% CI: 0.65-293.59, p = 0.09). The results remained statistically significant from different sensitivity analyses which represented the robustness of this meta-analysis. According to the NOS, 50.0% of the studies were considered as of high methodological quality (low risk of bias). No significant publication bias was detected from contour-enhanced and trim and fill funnel plots or Begg's and Egger's tests. This meta-analysis established that there is a significantly high prevalence of aPLs (i.e., aCL and anti-β2-GPI antibodies) in patients with BD when compared to controls.
BACKGROUND: Antiphospholipid antibodies (aPLs) namely anticardiolipin (aCL) antibody, anti-β2-glycoprotein I (β2GPI) antibody and lupus anticoagulant (LA) are autoantibodies produced against anionic phospholipids and proteins on plasma membranes. Migraine is a primary headache disorder which has growing evidences of autoimmune-mediated pathogenesis and previous studies suggested the presence of aPLs in migraine patients.
AIMS: The aim of this study was to evaluate the comorbid association between aPLs (aCL, anti-β2GPI and LA) and migraine compared to healthy controls.
METHODS: Studies were searched through PubMed, ISI Web of Science and Google Scholar databases without restricting the languages and year (up to October 2016) and were selected based on the inclusion criteria. Two authors independently extracted data from the included studies. All analyses were conducted by using random effects model to calculate the odds ratio (OR) and 95% confidence interval (CI). Quality assessment was carried out by using the modified Newcastle-Ottawa Scale (NOS). Publication bias was evaluated via visualization of funnel plots, Begg's and Egger's tests.
RESULTS: The database searches produced 1995 articles, 13 of which were selected (912 migraineurs and 822 healthy controls). 8.59%, 15.21% and 4.11% of the migraineurs exhibited aCL, anti-β2GPI and LA which was 4.83, 1.63 and 3.03 times higher, respectively, than healthy controls. A significant presence of aCL (OR: 3.55, 95% CI: 1.59-7.95; p=0.002) or anti-β2GPI antibodies (OR: 2.02, 95% CI: 1.20-3.42; p=0.008) was observed in migraine patients, however, LA was not significantly associated (OR: 2.02, 95% CI: 0.50-8.37; p=0.320). Majority of the studies (n=10 of 13) demonstrated NOS score of 7 or above and no significant publication bias was observed.
CONCLUSION: Migraine might be an autoimmune-associated neurologic disorder. The presence of aCL or anti-β2GPI antibodies was significant in migraine patients compared to healthy controls, suggesting an involvement of these autoantibodies in migraine attack.