Relevance of antiphospholipid antibodies in multiple sclerosis: A systematic review and meta analysis

The relationship between antiphospholipid antibodies (aPL) and multiple sclerosis (MS) is unclear.

To evaluate a link between aPL and MS.

EMBASE and PubMed search to August 2016; Peto's odds ratio (OR) meta-analysis.

The pooled prevalence of participants positive for IgG and IgM anticardiolipin (aCL) from 12 case-control studies was superior in MS than controls (6.8% vs 1.8%, p = 0.01 and 8.58% vs 2.18%, p = 0.001) with medium and high heterogeneities respectively (I² = 48.55% and 68.13%). The pooled prevalence of participants positive for IgG anti-beta₂glycoprotein-I (aβ₂GPI) from seven case-control studies was lower in MS than controls (0.93% vs 4.02%) with high heterogeneity (I² = 53.92%) though the pooled prevalence of participants positive for IgM aβ₂GPI was similar (7.24% vs 6.13%) with high heterogeneity (I² = 52.85%). Five cohorts compared IgG/IgM aCL and IgM aβ₂GPI in stable/remission vs active/relapsing MS: the pooled prevalence of IgG aCL was similar in active/relapsing and stable/remission MS (19% vs 18.9%) but the pooled prevalence of IgM aCL was higher in active than in stable MS (36.9% vs 21%, p < 0.0001) as well as that of IgM β₂GPI (40.5% vs 3.2%, p < 0.0001) with no heterogeneity.

Data from case-control studies do not support a link between IgG/IgM aPL and MS. Data from cohort studies comparing active vs stable MS indicate a strong link between aPL of IgM isotype and active/relapsing MS but in the absence of aPL titres to comment upon this may either represent an epiphenomenon of active neuro-inflammation or natural autoantibodies devoid of pathogenic potential. Data expressed as frequency of aPL positive participants rather than average titres preclude further assumptions.