Myelin basic protein autoantibodies, white matter disease and stroke outcome

Abstract

Antibodies to brain antigens are present in stroke survivors. In this study, we assessed autoantibody responses to white matter antigens, their correlation to white matter disease and stroke outcome. Antibody titers (immunoglobulin G [igG]) to myelin basic protein (MBP), proteolipid protein (PLP) and tetanus toxoid (TT) were available at one or more time points for 112 subjects with ischemic stroke. In comparison to the control subjects (N=40), there was a global decrease in IgG titers to TT early after stroke. Patients with white matter disease on magnetic resonance imaging had elevated titers of antibodies to both MBP and PLP at 30 days after stroke, and anti-MBP antibodies were associated with worse outcome. The potential pathologic consequences of antibodies to white matter, especially MBP, is deserving of further investigation.

Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke

“…Shibata and colleagues evaluated Ig titers in patients with IS, noting that stroke was associated with a quick decrease in the titer of anti-tetanus toxoid IgG antibodies; that patients with white matter disease showed higher IgG antibodies titers to MBP and proteolipid protein; and finally confirmed the above-mentioned findings by Becker and co-workers [121], showing worse long-term outcome in association with high antibody titers to MBP. This latter evidence is very interesting suggesting the real possibility that some antibodies do play a pivotal role in the pathophysiology of IS [122]. …”

Antibodies to myelin basic protein are associated with cognitive decline after stroke

“…Antibodies to CNS antigens like MBP, N-methyl-D-aspartate (NMDA) receptors and neurofilaments are detected in stroke survivors (Bornstein, Aronovich, 2001, Dambinova, Khounteev, 2003, Kalev-Zylinska, Symes, 2013, Shibata, Cain, 2012). Whether these antibodies are a mere epiphenomenon of brain injury or contribute to the late sequelae of stroke is unclear.…”

“…At least some of these autoantibodies could contribute to delayed cognitive dysfunction and other sequelae of stroke. What represents a clinically relevant increase in antibody titers is unknown, but it is clear that overall serum IgG falls after stroke (Liesz et al , 2015, Shibata, Cain, 2012). This observation suggests that comparing specific IgG titers of stroke patients to controls may be a flawed approach that underestimates the true effect of the antibodies that arise after stroke.…”

“…Serum antibody titers to MBP, PLP, and TT were determined in subjects with stroke as well as in controls as described (Shibata, Cain, 2012). Briefly, antibody titers (immunoglobulin G [IgG]) to TT were determined using a commercially available enzyme-linked immunosorbent assay (ELISA) kit (IBL International).…”

“…In human stroke survivors there are autoantibodies against brain antigens in blood (Bornstein et al , 2001, Dambinova et al , 2003, Kalev-Zylinska et al , 2013, Shibata et al , 2012) and B cells in the stroke lesions of those with dementia (Doyle, Quach, 2015). In addition to the humoral responses, cellular responses against brain antigens also occur after stroke and both appear to predictive of functional outcome (Becker et al , 2011, Becker et al , 2005, Shibata, Cain, 2012). The contribution of these immune responses to cognitive outcomes, however, has not been evaluated.…”