Neuropsychiatric Systemic Lupus Erythematosus: Molecules Involved in Its Imunopathogenesis, Clinical Features, and Treatment

Abstract

Systemic lupus erythematosus (SLE) is an idiopathic chronic autoimmune disease that can affect any organ in the body, including the neurological system. Multiple factors, such as environmental (infections), genetic (many HLA alleles including DR2 and DR3, and genes including C4), and immunological influences on self-antigens, such as nuclear antigens, lead to the formation of multiple autoantibodies that cause deleterious damage to bodily tissues and organs. The production of autoantibodies, such as anti-dsDNA, anti-SS(A), anti-SS(B), anti-Smith, and anti-neuronal DNA are characteristic features of this disease. This autoimmune disease results from a failure of the mechanisms responsible for maintaining self-tolerance in T cells, B cells, or both. Immune complexes, circulating antibodies, cytokines, and autoreactive T lymphocytes are responsible for tissue injury in this autoimmune disease. The diagnosis of SLE is a rheumatological challenge despite the availability of clinical criteria. NPSLE was previously referred to as lupus cerebritis or lupus sclerosis. However, these terms are no longer recommended because there is no definitive pathological cause for the neuropsychiatric manifestations of SLE. Currently, the treatment options are primarily based on symptomatic presentations. These include the use of antipsychotics, antidepressants, and anxiolytic medications for the treatment of psychiatric and mood disorders. Antiepileptic drugs to treat seizures, and immunosuppressants (e.g., corticosteroids, azathioprine, and mycophenolate mofetil), are directed against inflammatory responses along with non-pharmacological interventions.

Keywords: autoantibodies; biomarkers; cytokines; neuropsychiatric systemic lupus erythematosus; psychosis; steroids.

Figure 2

Immunopathogenesis of NPSLE. Modified from [39].

Figure 1

In Systemic lupus erythematosus (SLE), a type III hypersensitivity reaction occurs. This involves the formation of immune complexes that trigger the activation of the complement system. Two components of this system, C3a and C5a, serve as chemotactic factors. They draw neutrophils to the location where the immune complexes are deposited. The activation of these neutrophils results in inflammation and damage to the site, leading to conditions such as vasculitis, nephritis, and arthritis. There may also be other mechanisms at play. Adapted from [24].

Figure 3

Management for patients with NPSLE. Modified from [39].