Can Anti-AQP4 Antibody Damage the Blood-Brain Barrier?

Abstract

Background: Aquaporin 4 (AQP4) is a water-channel protein predominantly expressed in astrocyte end feet that make up the blood-brain barrier (BBB). Recently, anti-AQP4 antibody has been identified as a specific biomarker of neuromyelitis optica (NMO). However, whether anti-AQP4 antibodies damage the BBB is unclear. Methods: We evaluated BBB damage in patients with NMO and multiple sclerosis by measuring albumin leakage (AL) and studied its correlation with anti-AQP4 antibody. Results: No obvious difference in AL was observed between patients with and without anti-AQP4 antibodies. In the multivariate analysis, anti-AQP4 antibody was not associated with BBB damage. Of the anti-AQP4-positive patients, 58.0% had normal AL values, and the degree of BBB damage was unrelated to the anti-AQP4 antibody titer. In addition, 41.9% of anti-AQP4-positive patients showed no gadolinium enhancement of the MRI. Conclusion: These results indicate that the presence of anti-AQP4 antibody alone in plasma is insufficient to disrupt the BBB.

Blood Brain Barrier Permeability Could Be a Biomarker to Predict Severity of Neuromyelitis Optica Spectrum Disorders: A Retrospective Analysis

“…Secondly, we find that BBB permeability is positively correlated to serum anti-AQP4-IgG titer. Whether merely serum anti-AQP4 IgG is sufficient to induce BBB disturbance is controversial ( 4 , 6 ). Asgari et al reported the BBB disturbance in mice after administering with anti-AQP4-IgG from NMO patients ( 4 ).…”

“…Asgari et al reported the BBB disturbance in mice after administering with anti-AQP4-IgG from NMO patients ( 4 ). However, Akaza et al found that anti-AQP4-IgG was not associated with BBB damage ( 6 ). Our results further support the first perspective, and establish the quantitative link between BBB permeability and serum anti-AQP4-IgG titer.…”

“…The BBB permeability was measured using albumin index, which is the albumin level ratio, CSF/serum, as previously reported ( 6 , 17 ). The levels of albumin in the serum and CSF were measured using enzyme-linked immunosorbent assay kits (Debo, Shanghai, China).…”

“…Shimizu et al further found that anti-AQP4 IgG positive sera from NMO patients may disrupt BBB by reducing the expression of tight junction proteins ( 5 ). Notably, anti-AQP4-IgG may be not the only kind of autoantibody leading to the disruption of BBB ( 5 , 6 ). Many molecules have been found to be associated with the disturbance of BBB, including glucose-regulated protein 78 autoantibody, vascular endothelial growth factor, CD40, IL-6, and so on ( 5 , 7 – 9 ).…”

Quotient of cerebrospinal fluid/serum immunoglobulin G as a predictive factor for non‐responders to intravenous methylprednisolone therapy in patients with relapsing neuromyelitis optica spectrum disorder: Implication for early initiation of plasmapheresis

“…The clinical data consisted of IVMP efficacy, 10 clinical findings and four CSF parameters. The clinical findings comprised of: (i) age at relapse; (ii) sex; (iii) EDSS (at baseline before relapse, before IVMP initiation during relapse, at 7 days after IVMP initiation, at discharge and differences in EDSS, such as [i] increase in EDSS between at baseline and before IVMP: ΔEDSS [baseline – pre‐IVMP]; [ii] decrease in EDSS between before IVMP and at 7 days after IVMP: ΔEDSS [pre‐IVMP – post‐IVMP]; [iii] those between 7 days after IVMP and at discharge: ΔEDSS [post‐IVMP – discharge]; and [iv] those between before IVMP and at discharge: ΔEDSS [pre‐IVMP – discharge]); (iv) lesion site (spinal cord or brain); (v) gadolinium (Gd) enhanced lesion on MRI; (vi) number of relapses (the first attack was defined as one); (vii) complication with other autoantibodies (coexistence or not); (viii) immunosuppressant drugs (oral prednisolone [PSL] dose before relapse, mg/day; frequency of calcineurin inhibitor [CNI] use, %); (ix) total dose of IVMP used at the relapse phase (g/3−6 days); and (x) time‐period from exacerbation to IVMP initiation (days) . The CSF parameters consisted of: (i) CSF‐cells (count/μL); (ii) CSF‐lactate dehydrogenase (CSF‐LDH; IU/L); (iii) CSF/serum quotient of albumin (Q‐ALB; Q‐ALB × 10 3 ), which is a marker of the permeability of the blood–brain barrier (BBB); and (iv) CSF/serum quotient of immunoglobulin G (Q‐IgG; Q‐IgG × 10 3 ) .…”