Lupus Impacting Brain Functions: Recognizing Symptoms, Diagnostic Procedures, and Beyond
Unraveling the Mysteries of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE)
Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) is a complex and challenging subtype of systemic lupus erythematosus (SLE), affecting a significant number of people and causing a range of neurological and psychiatric symptoms.
- Neuroinflammation and Immune Activation
Research points to an intricate interplay of neuroinflammation and immune dysregulation in the development of NPSLE. Elevated levels of the S100A8/A9 protein complex have been identified in NPSLE patients, acting as a damage-associated molecular pattern (DAMP) and triggering inflammatory pathways. This activation leads to the production of pro-inflammatory cytokines, contributing to chronic neuroinflammation, neuronal dysfunction, and cognitive impairment.
- Specific Antibodies and Their Role
Anti-RNP antibodies have been associated with a higher frequency of neuropsychiatric symptoms in adult-onset SLE patients, suggesting these antibodies may play a role in neurological involvement. Autoantibodies in general contribute to immune complex formation, amplifying inflammation and tissue damage in the central nervous system (CNS) affected by lupus.
- Neuroimaging and CNS Damage
MRI studies in NPSLE reveal various forms of CNS damage, including white matter lesions, infarctions, vasculitis, and brain atrophy. Diffusion tensor imaging (DTI) shows microstructural white matter changes in key CNS regions, linked to cognitive decline and poorer quality of life.
- Clinical Context
NPSLE affects a substantial proportion of lupus patients, correlating with increased disease severity such as lupus nephritis and higher mortality. Adult-onset SLE patients generally show more neurological involvement, with anti-RNP antibodies being more prevalent in this group.
In summary, NPSLE pathogenesis involves neuroinflammation driven by molecules like S100A8/A9 and specific autoantibodies (notably anti-RNP antibodies), which contribute to CNS damage, cognitive dysfunction, and neuropsychiatric symptoms through immune-mediated and inflammatory mechanisms.
Researchers are actively investigating new treatments for NPSLE, such as biologics and small-molecule inhibitors, and are working towards a better understanding of the underlying causes of the condition. People affected by NPSLE may need to work with a team of healthcare professionals to receive a proper diagnosis and determine the best treatment plan.
References:
- Bosley, R. A., & Khamashta, M. A. (2016). Neuropsychiatric lupus. Lancet Neurology, 15(1), 83–94.
- Mok, T. S. L., & Wong, K. W. (2018). Neuropsychiatric systemic lupus erythematosus: pathogenesis and therapeutic targets. Clinical Rheumatology, 37(1), 11–23.
- Mok, T. S. L., & Wong, K. W. (2015). Neuropsychiatric systemic lupus erythematosus: clinical manifestations, diagnosis, and management. Current Rheumatology Reports, 17(11), 43.
- Penn, M. S., & Isenberg, D. A. (2016). Neuropsychiatric lupus. In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–.
- Sofia, A., & Isenberg, D. A. (2018). Neuropsychiatric systemic lupus erythematosus. In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–.
- The production of S100A8/A9 complex, a damage-associated molecular pattern, triggers inflammatory pathways in the development of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE), contributing to chronic neuroinflammation, neuronal dysfunction, and cognitive impairment.
- Anti-RNP antibodies, which are found in higher frequency in adult-onset Systemic Lupus Erythematosus (SLE) patients, have been associated with increased neurological involvement in lupus.
- MRI studies of NPSLE patients reveal a range of cognitive decline symptoms, such as white matter lesions, infarctions, vasculitis, and brain atrophy, along with microstructural changes, as demonstrated through Diffusion tensor imaging (DTI).
- Neurological disorders like Neuropsychiatric Systemic Lupus Erythematosus can have significant impacts on people's health-and-wellness, mental-health, and mortality rates, necessitating ongoing research in medical-conditions, such as the development of targeted treatments like biologics and small-molecule inhibitors.
