title: Comorbid association of antiphospholipid antibodies and migraine: A systematic review and meta-analysis.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
authors.forename: Md Asiful
authors.initials: MA
authors.lastname: Islam
authors.affiliation: Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
authors.forename: Fahmida
authors.initials: F
authors.lastname: Alam
authors.affiliation: Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia. Electronic address: kahkeng@usm.my.
authors.forename: Kah Keng
authors.initials: KK
authors.lastname: Wong
mesh_terms: D000293:Adolescent; D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000009:adverse effects* / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000150:complications* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D015897:Comorbidity; D005260:Female; D006801:Humans; D008881:Migraine Disorders / Q000150:complications*; D011446:Prospective Studies; D053482:beta 2-Glycoprotein I / Q000276:immunology
chemical_list: D017152:Antibodies, Antiphospholipid; D001323:Autoantibodies; D053482:beta 2-Glycoprotein I
keywords: Anti-β2-glycoprotein I antibodies; Anticardiolipin antibodies; Antiphospholipid antibodies; Lupus anticoagulant; Meta-analysis; Migraine