Associations with thrombosis are stronger for antiphosphatidylserine/prothrombin antibodies than for the Sydney criteria antiphospholipid antibody tests in SLE

Abstract

Objectives Antiphosphatidylserine/prothrombin complex antibodies (aPS/PT) are risk factors for thrombosis, yet further validation of their clinical relevance in different ethnic groups is required. We investigated the performance of aPS/PT of IgA/G/M isotypes among Sudanese and Swedish systemic lupus erythematosus (SLE) patients. Methods Consecutive SLE patients/matched controls from Sudan (n = 91/102) and Sweden (n = 332/163) were included. All patients fulfilled the 1982 ACR SLE classification criteria. IgA/G/M of aPS/PT, anti-cardiolipin and anti-β2glycoprotein I (anti-β2GPI) were tested in both cohorts, and lupus anticoagulant (LA) also in the Swedish cohort. Clinical antiphospholipid syndrome-related events and atherosclerosis, measured as carotid plaques were assessed for associations. Univariate and multivariate analyses adjusting for cardiovascular risk factors were performed. Results Sudanese SLE patients had higher levels of IgM aPS/PT, but using national cut-offs, the frequency of positivity was similar to Swedish patients for all isotypes. Among Swedish patients, all isotypes of aPS/PT associated with venous thromboembolism (VTE), while only IgA aPS/PT associated with arterial thrombosis (AT). aPS/PT antibodies associated strongly with LA and they were, independently, the best predictor for VTE. Double positivity for aPS/PT and anti-β2GPI associated with higher VTE risk than the conventional triple positivity. Carotid plaques did not associate with any antiphospholipid antibody. Conclusions IgA aPS/PT associated with AT, and the association of IgG/M aPS/PT with VTE outperforms LA and criteria antiphospholipid antibodies in Swedish SLE patients. Furthermore, double positivity for aPS/PT and anti-β2GPI performed better than conventional triple positivity. Future studies need to address if aPS/PT can replace LA, as this would simplify clinical procedures.

Added value of antiphosphatidylserine/prothrombin antibodies in the workup of thrombotic antiphospholipid syndrome: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies

“…While association of aPS/PT and venous thrombosis is clear, some have demonstrated no association between aPS/PT IgG/IgM and arterial thrombosis, 48,49 though others did 39,50 . Hoxha et al reported in 2017 that aPS/PT IgG, but not IgM, was more frequently positive in combined arterial and venous thrombosis, compared to arterial or venous thrombosis, although without higher median titers 43 .…”

Anti-phosphatidylserine/prothrombin antibodies and thrombosis associate positively with HLA-DRB1*13 and negatively with HLA-DRB1*03 in SLE

“…Arterial hypertension was defined as systolic and/or diastolic blood pressure ≥140/90 mmHg or use of antihypertensive medications. Diagnostic methods to establish clinical diagnoses were specified in our previous publication [ 18 ]. The Global APS Score (GAPSS) was calculated for all patients [ 23 ].…”

“…Quantification of aPS-PT, aCL and anti-β 2 GPI IgA/G/M was performed using the Aptiva system based on a particle-based multi-analyte technology (PMAT; research use only, Inova Diagnostics, San Diego, CA, USA [ 24 ]). Clinical associations for all aPL antibodies among patients were previously published in comparative studies between Sudan and Sweden, using a slightly lower number of Swedish patients ( n = 332) [ 18 , 21 ]. The 99th percentile values of 162 age- and sex-matched population controls were used as cut-offs [ 22 ].…”

“…More recently, positivity for aPS-PT has emerged as a risk factor for the presence of LA and vascular events [ 16 , 17 ]. In a recent publication we reported that aPS-PT antibodies associated more strongly with venous thromboembolism (VTE) and arterial thrombosis than did the conventional aPL [ 18 ]. In the current study we investigated a well-characterized Swedish SLE cohort regarding the relationship between HLA-DRB1 alleles, aPS-PT antibodies (IgG, IgM and IgA) and vascular events.…”

An Antiphospholipid Antibody Profile as a Biomarker for Thrombophilia in Systemic Lupus Erythematosus

“…The Hopkins Lupus Cohort reported that LA was the best predictor of the development of thrombosis in 821 SLE patients [ 24 ]. In an analysis of 332 Swedish SLE patients, LA positivity was the only independent risk factor for venous and arterial thrombosis [ 25 ]. A meta-analysis by Wahl et al also found that patients with SLE and LA had an approximately 3.5-fold increased risk of thrombosis (OR 3.56, 95%CI: 2.01–6.30) (arterial thrombosis OR 3.14, 95%CI: 1.41–6.97, venous thrombosis OR 4.89, 95%CI: 2.25–10.64) [ 26 ].…”