Antiphospholipid Antibodies as Key Players in Systemic Lupus Erythematosus: The Relationship with Cytokines and Immune Dysregulation

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by an overproduction of cytokines, such as interleukins and interferons, contributing to systemic inflammation and tissue damage. Antiphospholipid syndrome is a thrombo-inflammatory autoimmune disease affecting a third of SLE patients. We performed an in-depth analysis of the available literature, and we highlighted the complex interplay between immunity, inflammation, and thrombosis, the three major pathogenic pathways that are trapped in a mutually reinforcing destructive loop.

Keywords: antiphospholipid antibodies; antiphospholipid syndrome; immunity; inflammation; systemic lupus erythematosus; thrombosis.

Figure 1

Platelet receptors that interact with aPL antibodies (β2GPI = β2 glycoprotein I; GPIbα = glycoprotein Ibα; apoER2 = apolipoprotein E receptor 2,TLR = Toll-like receptors).

Figure 2

aPL antibodies change the endothelial phenotype from an antithrombotic to a prothrombotic one (NO = nitric oxide; PGI₂ = prostaglandin I₂; TF = tissue factor; AT III = antithrombin III; T = thrombin; TM = thrombomodulin; TFPI = tissue factor pathway inhibitor; tPA = tissue-type plasminogen activator; PAI-1 = plasminogen-activator inhibitor-1; ICAM-1 = intercellular adhesion molecule-1; VCAM-1 = vascular cell adhesion molecule-1; IL = interleukin; TNF-α tumor necrosis factor-alpha; eNOS = endothelial nitric oxide synthase; TX = thromboxane; IIa, Va, VIIa, VIIIa, IXa, Xa, XIa, XIIa = activated coagulation factors II, V, VII, VIII, IX, X, XI, XII, respectively).

Figure 3

Pathways of NET release triggered by aPL antibodies (TLR = Toll-like receptors; ROS = reactive oxygen species).

Figure 4

The complex interplay between thrombosis, inflammation, and the immune system (TF = tissue factor; ECs = endothelial cells; MAC = membrane attack complex; PAI-1 = plasminogen-activator inhibitor-1; IL = Interleukin; TNF-α = tumor necrosis factor-alpha; IFN = interferon; NETs = neutrophil extracellular traps).

Figure 5

The complex interaction between inflammation, immunity, and thrombosis, key contributors to the pathogenesis of SLE and APS.