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Antiphospholipid antibody levels in early systemic lupus erythematosus: are they associated with subsequent mortality and vascular events?

ABSTRACT: OBJECTIVES:aPL are present in between 20 and 30% of patients with SLE. They can cause vascular events (VE) or pregnancy morbidity. aCL and anti-beta-2-glycoprotein I (anti-?2GPI) are measured in clinical practice. Domain I (DI) of ?2GPI is the main site for aPL binding. We investigated the prevalence of IgG anti-DI, aCL and anti-?2GPI antibodies in early SLE and their association with mortality and development of VE. METHODS:Samples from 501 patients with SLE that had been obtained and stored early during their disease were tested for IgG anti-DI, aCL and anti-?2GPI antibodies by ELISA. LA status and history of VE were obtained by reviewing medical records. Kaplan-Meier analysis was used to investigate mortality and occurrence of VE, comparing groups with and without aPL in early disease. RESULTS:Of 501 patients, 190 (38%) had at least one of these aPL, of whom 112 had anti-DI alone. Of 276 patients with complete vascular history, 83 had experienced VE. The 39 patients who were double or triple-ELISA-positive for any combination of the three aPL were more likely to have or develop lupus anticoagulant (P<0.0001) than those who were single-ELISA-positive or negative. In Kaplan-Meier analysis, they showed a trend towards developing more VE (P = 0.06). CONCLUSION:IgG anti-DI antibodies were present in early serum samples from 29% of patients and were more common than IgG aCL or anti-?2GPI. There was some evidence suggesting that double or triple-ELISA-positivity for these antibodies identified a group with worse outcomes.

SUBMITTER: Pericleous C

PROVIDER: S-EPMC6909892 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Antiphospholipid antibody levels in early systemic lupus erythematosus: are they associated with subsequent mortality and vascular events?

Pericleous Charis C D'Souza Amrita A McDonnell Thomas T Ripoll Vera M VM Leach Oliver O Isenberg David D Giles Ian I Rahman Anisur A

Rheumatology (Oxford, England) 20200101 1

<h4>Objectives</h4>aPL are present in between 20 and 30% of patients with SLE. They can cause vascular events (VE) or pregnancy morbidity. aCL and anti-beta-2-glycoprotein I (anti-β2GPI) are measured in clinical practice. Domain I (DI) of β2GPI is the main site for aPL binding. We investigated the prevalence of IgG anti-DI, aCL and anti-β2GPI antibodies in early SLE and their association with mortality and development of VE.<h4>Methods</h4>Samples from 501 patients with SLE that had been obtaine ...[more]

PMID: 31257438

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Project description:Neutrophil Extracellular Traps (NETs) have been implicated in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) pathogenesis. The myeloperoxidase-deoxyribonucleic acid (MPO-DNA) complex and nucleosomes are serum markers of NETosis. The aim of this study was to assess these NETosis parameters as markers for SLE and APS diagnosis and their association with clinical features and disease activity. A total of 138 people were included in the cross-sectional study: 30 with SLE without APS, 47 with SLE and APS, 41 patients with primary antiphospholipid syndrome (PAPS), and 20 seemingly healthy individuals. Serum MPO-DNA complex and nucleosome levels were determined via an enzyme-linked immunosorbent assay (ELISA). Informed consent was obtained from all subjects involved in the study. The Ethics Committee of the V.A. Nasonova Research Institute of Rheumatology (Protocol No. 25 dated 23 December 2021) approved the study. In patients with SLE without APS, the levels of the MPO-DNA complex were significantly higher compared to patients with SLE with APS, with PAPS, and healthy controls (p < 0.0001). Among patients with a reliable diagnosis of SLE, 30 had positive values of the MPO-DNA complex, of whom 18 had SLE without APS, and 12 had SLE with APS. Patients with SLE and positive MPO-DNA complex levels were significantly more likely to have high SLE activity (χ2 = 5.25, p = 0.037), lupus glomerulonephritis (χ2 = 6.82, p = 0.009), positive antibodies to dsDNA (χ2 = 4.82, p = 0.036), and hypocomplementemia (χ2 = 6.72, p = 0.01). Elevated MPO-DNA levels were observed in 22 patients with APS: 12 with SLE with APS and 10 with PAPS. There were no significant associations between positive levels of the MPO-DNA complex and clinical and laboratory manifestations of APS. The concentration of nucleosomes was significantly lower in the group of SLE patients (±APS) compared to controls and PAPS (p < 0.0001). In SLE patients, the frequency of low nucleosome levels was associated with high SLE activity (χ2 = 13.4, p < 0.0001), lupus nephritis (χ2 = 4.1, p = 0.043), and arthritis (χ2 = 3.89, p = 0.048). An increase in the specific marker of NETosis, the MPO-DNA complex, was found in the blood serum of SLE patients without APS. Elevated levels of the MPO-DNA complex can be regarded as a promising biomarker of lupus nephritis, disease activity, and immunological disorders in SLE patients. Lower levels of nucleosomes were significantly associated with SLE (±APS). Low nucleosome levels were more common in patients with high SLE activity, lupus nephritis, and arthritis.

Dataset Information

Antiphospholipid antibody levels in early systemic lupus erythematosus: are they associated with subsequent mortality and vascular events?

Publications

Antiphospholipid antibody levels in early systemic lupus erythematosus: are they associated with subsequent mortality and vascular events?

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