Contributions
Abstract: EP1494
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Neurobiology
Blood-brain barrier (BBB) disruption is one of the key pathological processes involved in the Central Nervous System (CNS) autoimmunity. However, the exact role of BBB disruption in the immunopathomechanism of different CNS diseases with disseminated white matter lesions remains unknown. BBB damage may be defined by the increase of concentrations of cell adhesion molecules, which shed into the serum compartment upon BBB destruction. The aim of the present study was to assess the differences in the profile of BBB damage in relapsing-remitting multiple sclerosis (RRMS), neuromyelitis optica spectrum disorders (NMOsd) and neuropsychiatric systemic lupus erythematosus (NPSLE) patients.
We recruited 46 RRMS (median age 38), 19 NMOsd (median age 45) and 35 NPSLE patients (median age 32). All RRMS subjects were treatment-naïve, while NPSLE and NMOsd were on low doses of oral steroids plus azathioprine (NMOsd, NPSLE) or cyclophosphamide (NPSLE). Serum samples were obtained from study subjects and kept frozen at -80°C until further analysis. Serum sVCAM1, sPECAM1, sICAM1 , and VE-Cadherin levels were determined using ELISA, according to manufacturer´s instructions [BioVendor Laboratory Medicine, Inc. Czech Republik and R&D Systems Inc. Minneapolis].
We found that ICAM-1, PECAM-1 and VE-Cadherin serum levels were significantly lower in MS (median ICAM-1 386 ng/ml, PECAM-1 85 ng/ml, VE-Cadherin 4002 pg/ml) and NMOsd (median ICAM-1 319 ng/ml, PECAM-184 ng/ml, VE-Cadherin 4490 pg/ml) than in NPSLE (ICAM-1 median 483 ng/ml, PECAM-1 119 ng/ml, VE-Cadherin 6258 pg/ml). On the contrary, VCAM-1 was significantly higher in NMOsd (median 1024 ng/ml) than in MS (median 839 ng/ml), but comparable for MS and NPSLE (median 830 ng/ml).
To conclude, there is a different profile of cell adhesion molecules shedding in the spectrum of autoimmune CNS disorders with disseminated white matter lesions. Interestingly, all adhesion molecules levels, except for VCAM-1, are increased in NPSLE, as compared to NMOsd and MS. Although NMOsd is attributed to astrocyte pathology, and MS is primarily demyelinating, the pathomechanism of BBB disruption seems similar, especially when compared with lupus. Should these findings be repeated on larger populations, the BBB disruption profile could serve as another differentiation tool between MS, NMOsd and NPSLE.
Disclosure: The study was supported by the National Science Centre grant 2012/07/B/NZ6/03529.
Alicja Kalinowska-Lyszczarz (AKL), Mikolaj A. Pawlak (MAP), Slawomir Michalak (SM) and Wojciech Kozubski (WK) received speaker honoraria and/or travel grants and/or research grants from Teva Poland (AKL, MAP, SM, WK), Bayer Poland (AKL, SM, WK), Merck Poland (AKL, SM, WK), Novartis Poland (AKL, MAP, WK), Biogen Poland (AKL, MAP, SM, WK), Roche (AKL, MAP, SM, WK), Sanofi-Genzyme Poland (AKŁ, SM, WK). Ewa Wiesik-Szewczyk received speaker honoraria from CSL Behring, Shire and Kedrion. Katarzyna Pawlak-Bus, Piotr Leszczynski and Michalina Jasiak-Zatonska have nothing to disclose.
Abstract: EP1494
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Neurobiology
Blood-brain barrier (BBB) disruption is one of the key pathological processes involved in the Central Nervous System (CNS) autoimmunity. However, the exact role of BBB disruption in the immunopathomechanism of different CNS diseases with disseminated white matter lesions remains unknown. BBB damage may be defined by the increase of concentrations of cell adhesion molecules, which shed into the serum compartment upon BBB destruction. The aim of the present study was to assess the differences in the profile of BBB damage in relapsing-remitting multiple sclerosis (RRMS), neuromyelitis optica spectrum disorders (NMOsd) and neuropsychiatric systemic lupus erythematosus (NPSLE) patients.
We recruited 46 RRMS (median age 38), 19 NMOsd (median age 45) and 35 NPSLE patients (median age 32). All RRMS subjects were treatment-naïve, while NPSLE and NMOsd were on low doses of oral steroids plus azathioprine (NMOsd, NPSLE) or cyclophosphamide (NPSLE). Serum samples were obtained from study subjects and kept frozen at -80°C until further analysis. Serum sVCAM1, sPECAM1, sICAM1 , and VE-Cadherin levels were determined using ELISA, according to manufacturer´s instructions [BioVendor Laboratory Medicine, Inc. Czech Republik and R&D Systems Inc. Minneapolis].
We found that ICAM-1, PECAM-1 and VE-Cadherin serum levels were significantly lower in MS (median ICAM-1 386 ng/ml, PECAM-1 85 ng/ml, VE-Cadherin 4002 pg/ml) and NMOsd (median ICAM-1 319 ng/ml, PECAM-184 ng/ml, VE-Cadherin 4490 pg/ml) than in NPSLE (ICAM-1 median 483 ng/ml, PECAM-1 119 ng/ml, VE-Cadherin 6258 pg/ml). On the contrary, VCAM-1 was significantly higher in NMOsd (median 1024 ng/ml) than in MS (median 839 ng/ml), but comparable for MS and NPSLE (median 830 ng/ml).
To conclude, there is a different profile of cell adhesion molecules shedding in the spectrum of autoimmune CNS disorders with disseminated white matter lesions. Interestingly, all adhesion molecules levels, except for VCAM-1, are increased in NPSLE, as compared to NMOsd and MS. Although NMOsd is attributed to astrocyte pathology, and MS is primarily demyelinating, the pathomechanism of BBB disruption seems similar, especially when compared with lupus. Should these findings be repeated on larger populations, the BBB disruption profile could serve as another differentiation tool between MS, NMOsd and NPSLE.
Disclosure: The study was supported by the National Science Centre grant 2012/07/B/NZ6/03529.
Alicja Kalinowska-Lyszczarz (AKL), Mikolaj A. Pawlak (MAP), Slawomir Michalak (SM) and Wojciech Kozubski (WK) received speaker honoraria and/or travel grants and/or research grants from Teva Poland (AKL, MAP, SM, WK), Bayer Poland (AKL, SM, WK), Merck Poland (AKL, SM, WK), Novartis Poland (AKL, MAP, WK), Biogen Poland (AKL, MAP, SM, WK), Roche (AKL, MAP, SM, WK), Sanofi-Genzyme Poland (AKŁ, SM, WK). Ewa Wiesik-Szewczyk received speaker honoraria from CSL Behring, Shire and Kedrion. Katarzyna Pawlak-Bus, Piotr Leszczynski and Michalina Jasiak-Zatonska have nothing to disclose.