Antibodies to microtubule‐associated protein 2 in patients with neuropsychiatric systemic lupus erythematosus

Abstract

Objective. Microtubule-associated protein 2 (MAP-2), a cellular protein restricted to neurons, is important in the control of cytoskeletal integrity and other neuronal functions. We undertook this study to examine the presence of autoantibodies to MAP-2 in neuropsychiatric systemic lupus erythematosus (NPSLE).Methods. Sera from 100 patients with SLE, 74 patients with other neurologic disorders and injuries (including cerebrovascular accidents, brain trauma, brain tumors, and demyelinating disorders), and 60 normal controls were examined both by enzyme immunoassays and by Western immunoblotting for autoantibodies to MAP-2. Sera designated positive for antibodies to MAP-2 were required to be positive in both assays.Results. Seventeen percent of SLE patients had autoantibodies to MAP-2, in contrast to 4% of neurologic injury/disease control patients (P ‫؍‬ 0.028) and 1.7% of normal controls. In SLE, anti-MAP-2 positivity in both assays was associated with neuropsychiatric symptoms in 76.5% of patients, whereas the absence of anti-MAP-2 was associated with neuropsychiatric symptoms in 19.7% of patients (P ‫؍‬ 0.0002). The neuropsychiatric symptoms in the former group included psychosis, seizure, neuropathy, and cerebritis.Conclusion. Autoantibodies to MAP-2, a neuronrestricted cytoskeletal protein, appear to be another immune marker for NPSLE.

Characterization of discriminant human brain antigenic targets in neuropsychiatric systemic lupus erythematosus using an immunoproteomic approach

“…Using this approach, we confirmed recent reports by showing that MAP-2B and triosephosphate isomerase are brain antigenic targets in NPSLE (20,47,48). In contrast, anti-septin 7 antibodies were never observed in our patients with NPSLE.…”

“…Moreover, anti-triosephosphate isomerase antibodies have recently been found in CSF from patients with NPSLE (47). Whatever the pathogenic or regulatory role of anti-MAP-2B and anti-triosephosphate isomerase antibodies, they have recently been identified as good markers of NPSLE (20,48).…”

“…Several investigators have sought to identify autoantibodies that could bind directly to neurons and could serve as diagnostic markers in NPSLE (14)(15)(16)(17)(18)(19). Recently, sera collected from patients with SLE were tested for the presence of antibodies to microtubuleassociated protein 2 (MAP-2) and were detected in NPSLE patients in particular (20).…”

Pathogenesis of neurocognitive and neuropsychiatric manifestations in childhood-onset lupus: an overview

“…This is where MAP-2 is a cellular protein exclusively found in neurons, essential to cytoskeletal integrity so seems a plausible neurological antigen. 86,87 Ongoing work into glutamate receptor biology may be relevant in elucidating insights into the underlying pathogenesis of NPSLE. It is known that a subset of anti-dsDNA antibodies cross react with the N-methyl-D-aspartate receptor (NMDAR).…”

Relationship between elevated cerebrospinal fluid levels of plasminogen activator inhibitor 1 and neuronal destruction in patients with neuropsychiatric systemic lupus erythematosus

“…Levels of neuronal and astrocytic degradation products, such as neurofilament triplet protein (NFL) and glial fibrillary acidic protein (GFAP), are highly elevated in the cerebrospinal fluid (CSF) of SLE patients with neuropsychiatric involvement (5), suggesting that there is neuronal and astrocytic damage in this disease. Production of autoantibodies against brain structures (6,7), deposition of immune complexes in the central nervous system (CNS) (8), and intrathecal release of proinflammatory cytokines, e.g., interleukin-6 (IL-6) and IL-8 (9), may directly contribute to nervous system tissue injury. Besides immunologic processes, abnormalities of hemostasis might play a role in the pathogenesis of NPSLE, since one of the typical histopathologic changes found at autopsy in NPSLE patients is the presence of multifocal microinfarcts, seen particularly in the cerebral cortex and brain stem (10).…”