By Ana Espino | Published on May 6, 2026 | 4 min read
Systemic lupus erythematosus (SLE) is an autoimmune disease
characterized by the production of autoantibodies and systemic inflammation
that can affect multiple organs, including the central nervous system. When the
latter is involved, the condition is referred to as neuropsychiatric lupus
(NPSLE), a common and particularly disabling form that may affect up to 80% of
patients.
NPSLE encompasses a wide range of manifestations, from
cognitive impairment, fatigue, mood disorders, or psychosis, to more focal
conditions such as stroke or seizures. While some forms can be managed
symptomatically, diffuse central nervous system involvement remains difficult
to treat and represents a major unmet medical need.
The underlying mechanisms are complex and include systemic
inflammation, the production of brain-targeting autoantibodies, and disruption
of the blood–brain barrier, allowing these antibodies to enter brain tissue.
Despite therapeutic advances in SLE, few treatments specifically target these
manifestations, partly because NPSLE patients are often excluded from clinical
trials.
In this context, this review, recently published in Current
Opinion in Rheumatology, aims to provide an overview of current and
emerging treatments for NPSLE, highlighting new therapeutic strategies derived
from experimental models and clinical data.
What strategies to treat the brain ?
Current management relies primarily on immunosuppression. In
the acute phase, high-dose glucocorticoids, often combined with
cyclophosphamide, are the standard treatment. Other options such as rituximab,
intravenous immunoglobulins, or plasma exchange may be used in refractory
cases.
However, these treatments remain non-specific, and their
effectiveness in diffuse NPSLE is limited. Current and emerging therapeutic
strategies target several mechanisms: autoantibodies, systemic inflammation,
the blood–brain barrier, and neuroinflammation.
Emerging approaches include:
• Targeting B lymphocytes and autoantibodies, with therapies such as CAR T
cells or BTK inhibitors
• Reducing systemic inflammation, notably through JAK, TYK2 inhibitors, or
anti-interferon antibodies
• Direct neuroprotection, using molecules capable of limiting microglial
activation
Some innovative strategies also aim to directly block
pathogenic autoantibodies or prevent their interaction with neuronal targets.
A key element of the disease’s pathophysiology is the
integrity of the blood–brain barrier. Its increased permeability in lupus
patients facilitates the passage of neurotoxic antibodies into the brain.
Factors such as the gut microbiota or stress may modulate this barrier, opening
the way to novel therapeutic approaches.
Finally, recent studies highlight the central role of
microglia in sustaining brain inflammation. Angiotensin-converting enzyme (ACE)
inhibitors capable of crossing the blood–brain barrier appear to be a promising
avenue for limiting these neuroinflammatory processes.
Toward targeted treatments for NPSLE ?
Neuropsychiatric lupus remains a complex, poorly understood
condition that is difficult to treat, particularly in its diffuse forms. This
review highlights a major shift in the therapeutic paradigm, moving from broad
immunosuppression toward more targeted strategies.
New approaches—whether targeting B cells, inhibiting
cytokines, or modulating neuroinflammation—offer promising prospects for
improving patient management.
Beyond these advances, this work underscores the importance
of better including NPSLE patients in clinical trials to properly assess the
real-world effectiveness of these treatments. The next steps will be to
validate these strategies in dedicated clinical trials, deepen understanding of
the underlying mechanisms—particularly at the level of the blood–brain barrier
and microglia—and develop truly personalized treatments at the intersection of
immunology and neuroscience.
Read next : Lupus under
control?
About the author – Ana Espino
PhD in Immunology, specialized in Virology
As a scientific writer, Ana is passionate about bridging the gap
between research and real-world impact. With expertise in immunology, virology,
oncology, and clinical studies, she makes complex science clear and accessible.
Her mission: to accelerate knowledge sharing and empower evidence-based
decisions 
