Immunoglobulin A anti‐phospholipid antibodies in Swedish cases of systemic lupus erythematosus: associations with disease phenotypes, vascular events and damage accrual

Immunoglobulin A anti‐phospholipid antibodies in Swedish cases of systemic lupus erythematosus: associations with disease phenotypes, vascular events and damage accrual

Clinical & Experimental Immunology, September 2018

30208508

M. Frodlund, A. Vikerfors, G. Grosso, T. Skogh, J. Wetterö, K. Elvin, I. Gunnarsson, A. Kastbom, Ö. Dahlström, J. Rönnelid, E. Svenungsson, C. Sjöwall

Immunoglobulin (Ig) G- and IgM-class anti-cardiolipin antibodies (aCL) and lupus anti-coagulant (LA) are included in the 1997 update of the American College of Rheumatology (ACR-97) systemic lupus erythematosus (SLE) criteria. Despite limited evidence, IgA-aCL and IgA anti-β2 -glycoprotein-I (anti-β2 GPI) were included in the 2012 Systemic Lupus International Collaborating Clinics criteria. The present study aimed to evaluate IgG-/IgA-/IgM-aCL and anti-β2 GPI occurrence in relation to disease phenotype, smoking habits, pharmacotherapy, anti-phospholipid syndrome (APS) and organ damage among 526 Swedish SLE patients meeting ACR-97. Patients with rheumatoid arthritis (n = 100), primary Sjögren's syndrome (n = 50) and blood donors (n = 507) served as controls. Anti-phospholipid antibodies (aPL) were analysed by fluoroenzyme-immunoassays detecting aCL/anti-β2 GPI. Seventy-six (14%) SLE cases fulfilled the Sydney APS-criteria, and ≥ 1 aCL/anti-β2 GPI isotype (IgG/IgA/IgM) occurred in 138 SLE patients (26%). Forty-five (9%) of the SLE cases had IgA-aCL, 20 of whom (4%) lacked IgG-/IgM-aCL. Seventy-four (14%) tested positive for IgA anti-β2 GPI, 34 (6%) being seronegative regarding IgG/IgM anti-β2 GPI. Six (1%) had APS manifestations but were seropositive regarding IgA-aCL and/or IgA anti-β2 GPI in the absence of IgG/IgM-aPL and LA. Positive LA and IgG-aPL tests were associated with most APS-related events and organ damage. Exclusive IgA anti-β2 GPI occurrence associated inversely with Caucasian ethnicity [odds ratio (OR) = 0·21, 95% confidence interval (CI) = 0·06-0·72) and photosensitivity (OR = 0·19, 95% CI = 0·05-0·72). Nephritis, smoking, LA-positivity and statin/corticosteroid-medication associated strongly with organ damage, whereas hydroxychloroquine-medication was protective. In conclusion, IgA-aPL is not rare in SLE (16%) and IgA-aPL analysis may have additional value among SLE cases with suspected APS testing negative for other isotypes of aPL and LA.