Clinical significance of different antiphospholipid antibody isotypes in systemic lupus erythematosus

Abstract

Objective To investigate the prevalence and clinical significance of different subtypes (IgG, IgM and IgA) of anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I antibodies (aβ 2GP1), as well as lupus anticoagulant (LA) in systemic lupus erythematosus (SLE). Methods IgG/IgM/IgA, IgG, IgM, IgA aCL and anti-β2GP1 were tested by enzyme-linked immunosorbent assay (ELISA) in 100 patients with SLE (42 patients were diagnosed as secondary antiphospholipid syndrome), 44 healthy controls and 32 patients with other connective tissue diseases excluding SLE and antiphospholipid syndrome (APS). Meanwhile, LA was tested by modified Dilute Russell′s viper venom time (dRVVT). The correlation between antiphospholipid antibodies and clinical manifestation was analyzed by Spearman correlation analysis.The postiverate of antiphospholipid antibodies in SLE patients, health controls and patients with other connective tissue diseases were compared by chi square test. The concentrations of antiphospholipid antibodies in different groups were compared using independent sample Kruskal Wallis test. The diagnostic efficacy of antiphospholipid antibodies in SLE patients was analyzed by crosstable using clinical diagnosis of APS as gold standard. P<0.05 was considered statistically significant. Results The prevalence of IgG aCL(χ2=15.031 ,P<0.001), IgA/G/M (χ2=11.678, P=0.003) and IgA (χ2=6.17, P=0.036) anti-β2GP1 were significantly higher in patients with SLE than in the other two groups. IgA/G/M (r=0.207, P=0.039), IgG (r=0.230, P=0.021) and IgA (r=0.217, P=0.030) aCL, IgA/G/M (r=0.218, P=0.029) and IgA (r=0.255, P=0.01) anti-β2GP1, as well as LA (r=0.233, P=0.02) were associated with thrombotic events. IgA/G/M anti-β2GP1 (r=0.22, P=0.029) and LA (r=0.254, P=0.011) were associated with pathological pregnancy. 23.1% (6/26) aCL positive SLE patients were IgM and/or IgA aCL positive. 53.6% (15/28) anti-β2GP1 positive SLE patients were IgM and/or IgA anti-β2GP1 positive. In SLE patients, the specificity and sensitivity of IgA/G/M aCL for APS were 98.3% and 26.2%, respectively. The specificity and sensitivity of IgA/G/M anti-β2GP1 were 84.5% and 40.5%, respectively. The specificity of at least two isotypes positive for APS (both aCL and anti-β2GP1 were 98.3%), was higher than IgG aCL (94.8%) or anti-β2GP1 (93.1%). The sensitivity of at least one isotype of aCL (47.6%) or anti-β2GP1 (42.9%) positive for APS were higher than IgG aCL (40.5%) and anti-β2GP1 (21.4%). Conclusions IgG and IgM aCL together would be better than IgA/G/M aCL for APS screening. IgA/G/M anti-β2GP1 would be better for APS screen due to higher sensitivity and strong association with thromboembolic events and pathologic pregnance. IgA aCL or anti-β2GP1 was associated with thromboembolic events. IgA aCL or anti-β2GP1 would be useful for APS diagnosis in IgG and IgM aCL or anti-β2GP1 negative patients. （Chin J Lab Med,2014,37:597-602） Key words: Lupus erythematosus, systemic; Antiphospholipid syndrome; Immunoglobulins; Antibodies, anticardiolipin; beta 2-Glycoprotein I; Lupus coagulation inhibitor