Relationship between blood-brain permeability and antibodies against aquaporins in neuromyelitis optica spectrum disorders and multiple sclerosis patients

Aim of the study.To evaluate serum anti-aquaporin antibodies profile, to measure serum levels of cell-cell adhesion molecules as potential markers of blood-brain barrier (BBB) permeability, and to assess their relationship in neuromyelitis optica spectrum disorders (NMOsd) and multiple sclerosis (MS). Clinical rationale for the study. Serum levels of cell-cell adhesion molecules could provide information about BBB disruption in demyelinating diseases of the central nervous system. Improved knowledge about differences in their profile in NMOsd and MS patients, as well as about their relationship with antibody serostatus, would facilitate early and accurate diagnosis. Material and methods. Sera from 20 NMOsd and 59 MS patients were collected and assessed for anti-aquaporin 4 antibodies (AQP4-IgG) and antibodies against myelin oligodendrocyte glycoprotein (MOG-Ab) using an indirect immunofluorescence test (IIFT). Anti-aquaporin 1 antibodies (AQP1-Ab), vascular endothelial growth factor (VEGF), and vascular endothelial cadherin (VE-Cadherin) levels were assessed using commercial enzyme-linked immunosorbent assay (ELISA) kits. For occludin (OCLN) and claudin-5 (CLDN5) serum levels, we employed home-made ELISAs elaborated in the Department of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, Poland. Results. AQP4-IgG appeared only in 6/20 NMOsd patients who were all originally AQP4-IgG seropositive. All MS and NMOsd patients were seronegative for MOG-Ab. Patients with MS had higher AQP1-Ab levels than those with NMOsd (median 782.32 vs. 203.16 pg/mL; p < 0.001). CLND5 levels were significantly higher in MS than in NMOsd patients (median 1.65 vs. 1.00 ng/mL; p = 0.004). No statistically significant differences between MS and NMOsd were found for OCLN, VEGF and VE-Cadherin serum levels. In MS, AQ1-Ab levels were significantly lower in MS patients treated with immunomodulatory drugs vs. the treatment--naive(median 712.46 pg/mL vs. 942.73 pg/mL, respectively). There was a positive correlation between CLDN5 and OCLN in both the MS and the NMOsd groups. Conclusions and clinical implications.There is a different BBB disruption profile in MS and NMOsd, reflected by significantly higher CLDN5 and AQP1-Ab levels in MS samples. AQP1-Ab can be considered as a promising indicator of BBB disruption possibly associated with astrocytopathy.

Automated summary

The aim of this study was to evaluate the serum profile of anti-aquaporin antibodies, measure levels of cell-cell adhesion molecules as potential markers of blood-brain barrier permeability, and assess their relationship in NMOsd and MS patients. The results indicated a different profile of BBB disruption between MS and NMOsd patients, with AQP1-Ab identified as a promising indicator possibly associated with astrocytopathy.