Table 2.

Suggested pathogenetic factors in neuropsychiatric systemic lupus erythematosus

Genetic

TREX1 gene

HLA-DRB1*04

STAT4 rs10181656

Autoantibodies

Brain cells and constituents: neuronal, brain reactive, gangliosides, neurofilament (α-internexin), antibrain synaptosomal, anti-GFAP, anti-UCH-L1

Brain neurotransmitters: anti-NMDA/NR2, GABA-B

aCL/LAC/β2-glycoprotein I

Sm/Ro (SSA)/U1 RNP/ribosomal proteins/histone

Endothelial cells

Other: MAP2, serum lymphocytotoxic antibodies, triosephosphate isomerase, Hsp70, α-tubulin, peroxiredoxin 4, splicing factor, SFRS3, Nedd5

Cytokines

Interleukins: IL-1, IL-2, IL-6, IL-8, IL-10, TNF, APRIL, IFN-α, IFN-γ

Chemokines: CCL5, CCL2 (monocyte chemotactic protein 1), CXCL10 (IP-10)

Accelerated atherosclerosis

Traditional risk factors

Inflammatory risk factors

SLE-related risk factors (aCL and LAC, lupus nephritis, prednisone, low vitamin D)

Other SLE-specific factors

SLE disease activity/duration

Heart valve disease

Immune complexes

Complement deposition

Others

PAI-1

aCL anticardiolipin antibodies, APRIL a proliferation-inducing ligand, CCL chemokine ligand, CXCL C-X-C motif chemokine, IL interleukin, IFN interferon, GABA-B γ-aminobutyric acid type B receptors, GFAP glial fibrillary acid protein, HLA human leukocyte antigen, IP interferon γ-induced protein, LAC lupus anticoagulant, MAP2 microtubule-associated protein 2, NMDA/NR2 N-methyl-d-aspartate receptor, PAI plasminogen activator inhibitor, RNP ribonucleoprotein, SSA Sjögren’s syndrome-related antigen A, SLE systemic lupus erythematosus, TNF tumor necrosis factor, UCH-L1 ubiquitin carboxyl-terminal hydrolase isozyme L1