What are the autoantibodies associated with Systemic Lupus Erythematosus (SLE) and encephalitis?

From the Guidelines

Systemic Lupus Erythematosus (SLE) and Encephalitis Autoantibodies: The autoantibodies associated with SLE and encephalitis include anti-dsDNA, anti-C1q, anti-ENA, and antiphospholipid antibodies 1.

Key Autoantibodies

• Anti-dsDNA: a prominent immunological criterion in the EULAR/ACR 2019 classification, but not a homogeneous entity, with different antigenic specificities and binding capacities 1.
• Anti-C1q: associated with lupus nephritis, similar to anti-dsDNA 1.
• Anti-ENA: targets include chromatin, ribosomal P protein, spliceosome small nuclear ribonucleoproteins (Smith), Sjögren syndrome type A antigen (Ro), Sjögren syndrome type B antigen (La), and U1-ribonucleoprotein 1.
• Antiphospholipid antibodies: strong risk factors for cerebrovascular disease, seizures, and other neuropsychiatric manifestations in SLE patients 1.

Neuropsychiatric Manifestations

• Common manifestations include cerebrovascular disease and seizures, while relatively uncommon ones include severe cognitive dysfunction, major depression, acute confusional state, peripheral nervous disorders, and psychosis 1.
• Diagnostic work-up aims to exclude causes unrelated to SLE and may include cerebrospinal fluid analysis, EEG, neuropsychological tests, nerve conduction studies, and MRI 1.
• Treatment depends on the underlying mechanism, with glucocorticoids and immunosuppressive therapy indicated for inflammatory processes and antiplatelet/anticoagulation therapy for antiphospholipid antibody-related manifestations 1.

From the Research

Autoantibodies Associated with SLE and Encephalitis

• Autoantibodies associated with Systemic Lupus Erythematosus (SLE) include:
  • Anti-NMDA receptor autoantibodies, specifically anti-GluN2 antibodies 2
  • Anti-dsDNA autoantibodies, which are the most studied and have a pathogenic role in Lupus nephritis 3
  • Anti-β2GP1 antibodies, which are associated with vascular symptomatology 3
  • Anti-GluR3 autoantibodies, which have been found in patients with epilepsy and SLE 4
  • Autoantibodies against dsDNA, C1q, chromatin, Sm, and ribosomal P, which may serve as biomarkers of proliferative lupus nephritis 5
• Autoantibodies associated with encephalitis include:
  • Anti-NMDA receptor autoantibodies, specifically anti-GluN1 antibodies 2
  • Anti-GluR3 autoantibodies, which have been found in patients with encephalitis and can cause brain damage 4
  • NR2 autoantibodies, which have been detected in patients with encephalitis and can bind and kill hippocampal and cortical neurons 4

Pathogenic Mechanisms

• These autoantibodies can cause brain damage and tissue inflammation through various mechanisms, including:
  • Altering synaptic composition and gating of NMDA receptors 2
  • Activating glutamate-receptor antigen and causing neuronal death 4
  • Binding to and killing hippocampal and cortical neurons through an excitotoxic complement-independent mechanism 4

Clinical Significance

• The presence of these autoantibodies can inform about disease susceptibility, clinical course, and outcomes in SLE and encephalitis 3, 6, 5
• Identifying pathogenic autoantibodies remains a significant challenge, but recent advances in high-throughput technologies and innovative hypothesis have led to the discovery of functional autoantibodies linked to pathogenic pathways in SLE 5