The blood brain barrier and neuropsychiatric lupus: new perspectives in light of advances in understanding the neuroimmune interface

Abstract

Experts have previously postulated a linkage between lupus associated vascular pathology and abnormal brain barriers in the immunopathogenesis of neuropsychiatric lupus. Nevertheless, there are some discrepancies between the experimental evidence, or its interpretation, and the working hypotheses prevalent in this field; specifically, that a primary contributor to neuropsychiatric disease in lupus is permeabilization of the blood brain barrier. In this commonly held view, any contribution of the other known brain barriers, including the blood-cerebrospinal fluid and meningeal barriers, is mostly excluded from the discussion. In this review we will shed light on some of the blood brain barrier hypotheses and try to trace their roots. In addition, we will suggest new research directions to allow for confirmation of alternative interpretations of the experimental evidence linking the pathology of intra-cerebral vasculature to the pathogenesis of neuropsychiatric lupus.

Tertiary lymphoid structures in the choroid plexus in neuropsychiatric lupus

“…Furthermore, our recent work evaluating BBB function and routes of immune penetration into the CNS has proved revealing in the model used herein; BBB function in particular as it relates to interendothelial tight junctions appears to be mostly conserved, and the CP is in fact a conduit for immunoglobulin transmission and lymphocyte migration (37). The various potential modes of immune migration through the CNS in SLE have been recently reviewed, including discussion of the relative roles of the BBB and CP, as well as the potential involvement of dural lymphatics and the glymphatic pathways (46).…”

“…However, the relationship between serum autoantibodies and brain pathology in SLE is inconsistent (41)(42)(43)(44). Although there has been speculation regarding potential routes of entry for neuropathic autoantibodies into the CNS of patients with SLE (45), there is little direct evidence of blood-brain barrier (BBB) or other blood-CNS barrier disruption (46). This does not, however, preclude production of neuropathic autoantibodies in localized, ectopic lymphoid structures, as has been recently reported in lupus nephritis (22).…”

Neuropsychiatric Lupus Erythematosus: Future Directions and Challenges; a Systematic Review and Survey

“…This syndrome is different from other aspects of SLE because it can occur without any serological changes. Focal disease in the form of focal seizures or stroke is caused by lupus-related coagulopathies (6). However, diffuse disease varies considerably among patients; symptoms include memory impairment, anxiety, general cognitive decline, and depression (7).…”

Neuropsychiatric SLE: From Immune Mechanisms to Clinical Management

“…The brain is immunoprivileged due to the existence of multiple barriers regulating entry of immune cells and compounds such as antibodies. As a result, it has long been thought that some kinds of disruption in these barriers are necessary for NPSLE disease to manifest [19]. This notion is further supported by the observation that some SLE patients have brain reactive autoantibodies in their sera but do not have neuropsychiatric disease [20,21].…”