open access

Vol 56, No 3 (2022)
Research Paper
Submitted: 2021-10-13
Accepted: 2022-01-11
Published online: 2022-02-04
Get Citation

Different blood-brain-barrier disruption profiles in multiple sclerosis, neuromyelitis optica spectrum disorders, and neuropsychiatric systemic lupus erythematosus

Michalina Jasiak-Zatońska1, Anna Pietrzak2, Aleksandra Wyciszkiewicz2, Ewa Więsik-Szewczyk3, Katarzyna Pawlak-Buś4, Piotr Leszczyński4, Wojciech Kozubski2, Sławomir Michalak1, Alicja Kalinowska-Łyszczarz1
·
Pubmed: 35118639
·
Neurol Neurochir Pol 2022;56(3):246-255.
Affiliations
  1. Department of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, Poznan, Poland
  2. Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland
  3. Department of Internal Medicine, Pulmonology, Allergy and Clinical Immunology, Central Clinical Hospital of the Ministry of National Defence, Military Institute of Medicine, Warsaw, Poland
  4. Department of Rheumatology, Rehabilitation and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland

open access

Vol 56, No 3 (2022)
RESEARCH PAPERS — LEADING TOPIC
Submitted: 2021-10-13
Accepted: 2022-01-11
Published online: 2022-02-04

Abstract

Aim of the study. To assess differences in BBB damage profiles by measuring serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and S100 calcium-binding protein B (S100B) in relapsing-remitting multiple sclerosis (RRMS), neuromyelitis optica spectrum disorders (NMOsd), and neuropsychiatric systemic lupus erythematosus (NPSLE) patients.

Clinical rationale for the study. Blood-brain-barrier (BBB) disruption is one of the key pathological processes involved in various demyelinating diseases of the central nervous system (CNS) and is associated with shedding of cell adhesion molecules and S100B into the serum compartment. Therefore, making an assessment of serum levels of the above-mentioned molecules could provide information about disease pathogenesis, severity of BBB disruption, and disease activity.

Material and methods. We recruited 42 RRMS, 19 NMOsd and 35 NPSLE patients. Subjects were treated with beta-interferons or glatiramer acetate (RRMS), oral steroids and/or azathioprine (NMOsd, NPSLE), other immunosuppressants (NPSLE), or antimalarials (NPSLE). The clinical condition of the patients was assessed using the Kurtzke Expanded Disability Status Scale for MS and NMOsd, and the Systemic Lupus Erythematosus Disease Activity Index for NPSLE. Serum levels of sVCAM-1, sPECAM-1, sICAM-1 and S100B were determined using enzyme-linked immunosorbent assay (ELISA).

Results. We found the lowest levels of sPECAM-1, sICAM-1 and S100B in sera from NMOsd patients. The highest levels of sPECAM-1 and sICAM-1 were observed in NPSLE, and in NPSLE and MS, respectively. There were no statistically significant differences in sVCAM-1 levels between the examined groups. In MS and NMOsd, there was a negative correlation between the EDSS score and the following molecules: sPECAM-1, sICAM-1 and S100B.

Conclusions and clinical implications. We conclude that there is a different profile of blood-brain-barrier disruption reflected by cell adhesion molecules shedding in the spectrum of autoimmune CNS disorders with disseminated white matter lesions. These molecules could become new biomarkers to be used in CNS demyelinating diseases differential diagnoses and monitoring disease activity, but further studies on larger groups of patients are necessary.

Abstract

Aim of the study. To assess differences in BBB damage profiles by measuring serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and S100 calcium-binding protein B (S100B) in relapsing-remitting multiple sclerosis (RRMS), neuromyelitis optica spectrum disorders (NMOsd), and neuropsychiatric systemic lupus erythematosus (NPSLE) patients.

Clinical rationale for the study. Blood-brain-barrier (BBB) disruption is one of the key pathological processes involved in various demyelinating diseases of the central nervous system (CNS) and is associated with shedding of cell adhesion molecules and S100B into the serum compartment. Therefore, making an assessment of serum levels of the above-mentioned molecules could provide information about disease pathogenesis, severity of BBB disruption, and disease activity.

Material and methods. We recruited 42 RRMS, 19 NMOsd and 35 NPSLE patients. Subjects were treated with beta-interferons or glatiramer acetate (RRMS), oral steroids and/or azathioprine (NMOsd, NPSLE), other immunosuppressants (NPSLE), or antimalarials (NPSLE). The clinical condition of the patients was assessed using the Kurtzke Expanded Disability Status Scale for MS and NMOsd, and the Systemic Lupus Erythematosus Disease Activity Index for NPSLE. Serum levels of sVCAM-1, sPECAM-1, sICAM-1 and S100B were determined using enzyme-linked immunosorbent assay (ELISA).

Results. We found the lowest levels of sPECAM-1, sICAM-1 and S100B in sera from NMOsd patients. The highest levels of sPECAM-1 and sICAM-1 were observed in NPSLE, and in NPSLE and MS, respectively. There were no statistically significant differences in sVCAM-1 levels between the examined groups. In MS and NMOsd, there was a negative correlation between the EDSS score and the following molecules: sPECAM-1, sICAM-1 and S100B.

Conclusions and clinical implications. We conclude that there is a different profile of blood-brain-barrier disruption reflected by cell adhesion molecules shedding in the spectrum of autoimmune CNS disorders with disseminated white matter lesions. These molecules could become new biomarkers to be used in CNS demyelinating diseases differential diagnoses and monitoring disease activity, but further studies on larger groups of patients are necessary.

Get Citation

Keywords

blood-brain barrier breakdown, multiple sclerosis, systemic lupus erythematosus, neuromyelitis optica spectrum disorders, adhesion molecules

Supp./Additional Files (3)
Supplementary Figure 1
View
45KB
Supplementary Table 1
Download
14KB
Supplementary Table 2
Download
15KB
About this article
Title

Different blood-brain-barrier disruption profiles in multiple sclerosis, neuromyelitis optica spectrum disorders, and neuropsychiatric systemic lupus erythematosus

Journal

Neurologia i Neurochirurgia Polska

Issue

Vol 56, No 3 (2022)

Article type

Research Paper

Pages

246-255

Published online

2022-02-04

Page views

5392

Article views/downloads

1192

DOI

10.5603/PJNNS.a2022.0013

Pubmed

35118639

Bibliographic record

Neurol Neurochir Pol 2022;56(3):246-255.

Keywords

blood-brain barrier breakdown
multiple sclerosis
systemic lupus erythematosus
neuromyelitis optica spectrum disorders
adhesion molecules

Authors

Michalina Jasiak-Zatońska
Anna Pietrzak
Aleksandra Wyciszkiewicz
Ewa Więsik-Szewczyk
Katarzyna Pawlak-Buś
Piotr Leszczyński
Wojciech Kozubski
Sławomir Michalak
Alicja Kalinowska-Łyszczarz

References (50)
  1. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018; 17(2): 162–173.
  2. Lennon VA, Kryzer TJ, Pittock SJ, et al. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med. 2005; 202(4): 473–477.
  3. Sato DK, Callegaro D, Lana-Peixoto MA, et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology. 2014; 82(6): 474–481.
  4. Jasiak-Zatońska M, Michalak S, Osztynowicz K, et al. Relationship between blood-brain permeability and antibodies against aquaporins in neuromyelitis optica spectrum disorders and multiple sclerosis patients. Neurol Neurochir Pol. 2022 [Epub ahead of print].
  5. Mostafa GA, Ibrahim DH, Shehab AA, et al. The role of measurement of serum autoantibodies in prediction of pediatric neuropsychiatric systemic lupus erythematosus. J Neuroimmunol. 2010; 227(1-2): 195–201.
  6. Magro Checa C, Cohen D, Bollen EL, et al. Demyelinating disease in SLE: is it multiple sclerosis or lupus? Best Pract Res Clin Rheumatol. 2013; 27(3): 405–424.
  7. Wingerchuk D. Neuromyelitis spectrum disorders. Continuum: Lifelong Learning in Neurology. 2010; 16: 105–121.
  8. Unterman A, Nolte JES, Boaz M, et al. Neuropsychiatric syndromes in systemic lupus erythematosus: a meta-analysis. Semin Arthritis Rheum. 2011; 41(1): 1–11.
  9. Mok MoY, Chan EYT, Wong WS, et al. Intrathecal immunoglobulin production in patients with systemic lupus erythematosus with neuropsychiatric manifestations. Ann Rheum Dis. 2007; 66(6): 846–847.
  10. Wingerchuk DM, Hogancamp WF, O'Brien PC, et al. The clinical course of neuromyelitis optica (Devic's syndrome). Neurology. 1999; 53(5): 1107–1114.
  11. Wingerchuk D, Lennon V, Lucchinetti C, et al. The spectrum of neuromyelitis optica. The Lancet Neurology. 2007; 6(9): 805–815.
  12. Wang Y, Zhu M, Liu C, et al. Blood Brain Barrier Permeability Could Be a Biomarker to Predict Severity of Neuromyelitis Optica Spectrum Disorders: A Retrospective Analysis. Front Neurol. 2018; 9: 648.
  13. Tomizawa Y, Yokoyama K, Saiki S, et al. Blood-brain barrier disruption is more severe in neuromyelitis optica than in multiple sclerosis and correlates with clinical disability. J Int Med Res. 2012; 40(4): 1483–1491.
  14. Elovaara I, Lällä M, Spåre E, et al. Methylprednisolone reduces adhesion molecules in blood and cerebrospinal fluid in patients with MS. Neurology. 1998; 51(6): 1703–1708.
  15. Rieckmann P, Altenhofen B, Riegel A, et al. Soluble adhesion molecules (sVCAM-1 and sICAM-1) in cerebrospinal fluid and serum correlate with MRI activity in multiple sclerosis. Ann Neurol. 1997; 41(3): 326–333.
  16. Losy J, Niezgoda A, Wender M. Increased serum levels of soluble PECAM-1 in multiple sclerosis patients with brain gadolinium-enhancing lesions. J Neuroimmunol. 1999; 99(2): 169–172.
  17. Dore-Duffy P, Washington R, Dragovic L. Expression of endothelial cell activation antigens in microvessels from patients with multiple sclerosis. Adv Exp Med Biol. 1993; 331: 243–248.
  18. Albelda S, Buck C. Integrins and other cell adhesion molecules. The FASEB Journal. 1990; 4(11): 2868–2880.
  19. Albelda S, Smith C, Ward P. Adhesion molecules and inflammatory injury. The FASEB Journal. 1994; 8(8): 504–512.
  20. Elangbam CS, Qualls CW, Dahlgren RR. Cell Adhesion Molecules—Update. Veterinary Pathology. 2016; 34(1): 61–73.
  21. Yang L, Froio RM, Sciuto TE, et al. ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-alpha-activated vascular endothelium under flow. Blood. 2005; 106(2): 584–592.
  22. Muller WA, Weigl SA, Deng X, et al. PECAM-1 is required for transendothelial migration of leukocytes. J Exp Med. 1993; 178(2): 449–460.
  23. Woodfin A, Voisin MB, Nourshargh S. PECAM-1: a multi-functional molecule in inflammation and vascular biology. Arterioscler Thromb Vasc Biol. 2007; 27(12): 2514–2523.
  24. Donato R, Cannon BR, Sorci G, et al. Functions of S100 proteins. Curr Mol Med. 2013; 13(1): 24–57.
  25. Michetti F, Corvino V, Geloso MC, et al. The S100B protein in biological fluids: more than a lifelong biomarker of brain distress. J Neurochem. 2012; 120(5): 644–659.
  26. Sedaghat F, Notopoulos A. S100 protein family and its application in clinical practice. Hippokratia. 2008; 12(4): 198–204.
  27. Marchi N, Cavaglia M, Fazio V, et al. Peripheral markers of blood-brain barrier damage. Clin Chim Acta. 2004; 342(1-2): 1–12.
  28. Wingerchuk DM, Banwell B, Bennett JL, et al. International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015; 85(2): 177–189.
  29. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011; 69(2): 292–302.
  30. Nived O, Sturfelt G, Liang MH, et al. The ACR nomenclature for CNS lupus revisited. Lupus. 2003; 12(12): 872–876.
  31. Chang BL, Ro LS, Chen CM, et al. Serum levels of cell adhesion molecules in patients with neuromyelitis optica spectrum disorder. Ann Clin Transl Neurol. 2020; 7(10): 1854–1861.
  32. Uzawa A, Mori M, Masuda S, et al. Markedly elevated soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1 levels, and blood-brain barrier breakdown in neuromyelitis optica. Arch Neurol. 2011; 68(7): 913–917.
  33. Kapica-Topczewska K, Collin F, Tarasiuk J, et al. Clinical and epidemiological characteristics of multiple sclerosis patients receiving disease-modifying treatment in Poland. Neurol Neurochir Pol. 2020; 54(2): 161–168.
  34. Elovaara I, Ukkonen M, Leppäkynnäs M, et al. Adhesion molecules in multiple sclerosis: relation to subtypes of disease and methylprednisolone therapy. Arch Neurol. 2000; 57(4): 546–551.
  35. Rieckmann P, Altenhofen B, Riegel A, et al. Correlation of soluble adhesion molecules in blood and cerebrospinal fluid with magnetic resonance imaging activity in patients with multiple sclerosis. Mult Scler. 1998; 4(3): 178–182.
  36. Giovannoni G, Lai M, Thorpe J, et al. Longitudinal study of soluble adhesion molecules in multiple sclerosis: correlation with gadolinium enhanced magnetic resonance imaging. Neurology. 1997; 48(6): 1557–1565.
  37. Hartung HP, Reiners K, Archelos JJ, et al. Circulating adhesion molecules and tumor necrosis factor receptor in multiple sclerosis: correlation with magnetic resonance imaging. Ann Neurol. 1995; 38(2): 186–193.
  38. Minagar A, Jy W, Jimenez JJ, et al. Elevated plasma endothelial microparticles in multiple sclerosis. Neurology. 2001; 56(10): 1319–1324.
  39. Minagar A, Alexander JS. Blood-brain barrier disruption in multiple sclerosis. Mult Scler. 2003; 9(6): 540–549.
  40. da Rosa Franchi Santos LF, Stadtlober NP, Costa Dall'Aqua LG, et al. Increased adhesion molecule levels in systemic lupus erythematosus: relationships with severity of illness, autoimmunity, metabolic syndrome and cortisol levels. Lupus. 2018; 27(3): 380–388.
  41. Janssen BA, Luqmani RA, Gordon C, et al. Correlation of blood levels of soluble vascular cell adhesion molecule-1 with disease activity in systemic lupus erythematosus and vasculitis. Br J Rheumatol. 1994; 33(12): 1112–1116.
  42. Lassmann H. Pathology and disease mechanisms in different stages of multiple sclerosis. J Neurol Sci. 2013; 333(1-2): 1–4.
  43. Shimizu F, Nishihara H, Kanda T. Blood-brain barrier dysfunction in immuno-mediated neurological diseases. Immunol Med. 2018; 41(3): 120–128.
  44. Małecka I, Przybek-Skrzypecka J, Kurowska K, et al. Clinical and laboratory parameters by age for patients diagnosed with multiple sclerosis between 2000 and 2015. Neurol Neurochir Pol. 2021; 55(4): 387–393.
  45. Massaro AR, Michetti F, Laudisio A, et al. Myelin basic protein and S-100 antigen in cerebrospinal fluid of patients with multiple sclerosis in the acute phase. Ital J Neurol Sci. 1985; 6(1): 53–56.
  46. Missler U, Wandinger KP, Wiesmann M, et al. Acute exacerbation of multiple sclerosis increases plasma levels of S-100 protein. Acta Neurol Scand. 1997; 96(3): 142–144.
  47. Bartosik-Psujek H, Psujek M, Jaworski J, et al. Total tau and S100b proteins in different types of multiple sclerosis and during immunosuppressive treatment with mitoxantrone. Acta Neurol Scand. 2011; 123(4): 252–256.
  48. Schenatto CB, Xavier RM, Bredemeier M, et al. Raised serum S100B protein levels in neuropsychiatric lupus. Ann Rheum Dis. 2006; 65(6): 829–831.
  49. Yang Xy, Lin J, Lu Xy, et al. Expression of S100B protein levels in serum and cerebrospinal fluid with different forms of neuropsychiatric systemic lupus erythematosus. Clin Rheumatol. 2008; 27(3): 353–357.
  50. Fujii C, Tokuda T, Ishigami N, et al. Usefulness of serum S100B as a marker for the acute phase of aquaporin-4 autoimmune syndrome. Neurosci Lett. 2011; 494(1): 86–88.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp. z o.o., ul. Świętokrzyska 73, 80–180 Gdańsk, Poland
tel.:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: viamedica@viamedica.pl