Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by heterogeneity of presentation, an undulating course, and elevated risk for premature cardiovascular disease. Platelets have been understudied as a relevant contributor. Yet, these cells, which contain transcripts and the necessary molecular machinery to conduct translation, are intercellular regulators of inflammation and immune activation and play a key role in atherothrombosis. Platelets express low affinity type 2 receptors (FcγRIIA) whose ligand is the Fc portion of IgG. A single amino acid substitution, H131R, in the extracellular ligand binding domain increases the affinity for IgG and may account for individual variation in platelet activation, specifically an increase of function. Accordingly, this study addressed the hypothesis that FcyRIIA genotype associates with preclinical atherosclerosis and platelet hyperreactivity.
Methods: Genotyping at rs1801274 (allelic discrimination, HWE P=NS) was performed in 71 SLE patients and 30 healthy controls. In 49 of the SLE patients and 30 healthy controls, carotid ultrasound for plaque (≥50% increase over background IMT in any arterial segment); levels of soluble E-selectin as a proxy of endothelial cell activation; and C3, C4 to reflect complement activation were assessed. In 22 SLE patients, monocyte-platelet (MPA) and leukocyte-platelet aggregates (LPA), and light transmission aggregometry (LTA) in response to submaximal concentrations of collagen and arachidonic acid were evaluated.
Results: Overall genotyping for FcγRIIA revealed 43 SLE patients carrying at least one copy of the variant allele and 28 patients who were homozygous for the ancestral allele. For the 49 with IMT, carotid plaque was reported in 22. A significant enrichment of carotid plaque was identified in patients with a variant compared to those who were homozygous ancestral (58% vs 25%, p=0.039). In contrast, among 30 healthy controls, the presence of carotid plaque was not associated with the variant or ancestral genotype (15% vs 15%). Soluble E-selectin (mean + 2SD, shown as dichotomous being above normal controls) was significantly increased in those patients with the variant vs ancestral (64% vs 23%, p=0.013). Complement levels, a proxy of circulating immune complexes, were lower in patients with the variant vs ancestral (64% vs 40%). With regard to platelet reactivity, among 22 SLE subjects evaluated, there was a significant increase in MPA and LPA (above controls, mean + 2SD) in those carrying at least one variant compared to the ancestral group (86% vs 37%, p=0.02 and 46% vs 12%, p=0.05, respectively). Platelet aggregation was more robust for those patients with the variant vs ancestral in response to 160 uM arachidonic acid and 1 ug/mL collagen (47% vs 19% and 47% vs 14%, respectively).
Conclusion: These data suggest a model in which an FcγRIIA polymorphism associates with preclinical atherosclerosis and confers increased platelet activity in the setting of SLE, a disease characterized by circulating immune complexes.
To cite this abstract in AMA style:Rasmussen S, Reynolds H, Buyon JP, Nhek S, Newman J, Berger J, Clancy RM. Platelet FcγRIIa Polymorphism H131R Associates with Subclinical Atherosclerosis and Increased Platelet Activity in SLE [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/platelet-fc%ce%b3riia-polymorphism-h131r-associates-with-subclinical-atherosclerosis-and-increased-platelet-activity-in-sle/. Accessed July 11, 2020.
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