BOTULINUM NEUROTOXIN (BONT/A) AS AN INDUCER OF ACUTE ANTERIOR UVEITIS IN HLA B27 PATIENTS: A LITERATURE REVIEW
DOI:
https://doi.org/10.53555/yxrfep25Keywords:
HLA B27, Anterior Uveitis, Botulinum Neurotoxin, AntigenAbstract
Background: HLA B27 related acute anterior uveitis is a chronic recurrent inflammation of uvea mainly in anterior chamber. The underlying mechanism seems to involves autoimmunity and autoinflammatory. Antigen has been proposed as a trigger, but its precise role is unclear.
Aim: We systematically searched evidence for the involvement of antigen, including BoNT/A in triggering HLA-B27 associated disease.
Methods: We searched four data base including Pubmed, Ebscohost, Sciencedirect, and Google Scholar. We also review the immunologic response to BoNT/A, its amino acid sequence, and homology with human protein
Results: Eight studies reviewed which include the role of antigen in triggering uveitis. Four studies favour autoinflammatory pathway which involves B27 homodimer formation and its interaction with TH-17. Four studies favour autoimmunity pathway which involves molecular mimicry and activation of self reactive CD8+ T-Cells. All of which centralize the role of dendritic cells as antigen presenting cells. Five studies describe immune response to BoNT/A. BoNT/A capable of activating innate and immune system. Using BLAST program from NCBI, we found BoNT/A homology with cytokeratine 8.
Conclusion: Two possible pathway on how antigen might trigger HLA B27 AAU. The first is through uveitogenic capacity of the antigen. The second mechanism is through homodimer formation. BoNT/A might induce uveitis in HLA B27 individual through induction of homodimer and activation of self-reactive CD8+ T-Cells due to shared homology with cytokeratine 8 that is extensively expressed in human uvea
References
Tsirouki T, Dastiridou A, Symeonidis C, Tounakaki O, Brazitikou I, Kalogeropoulos C, et al. A Focus on the Epidemiology of Uveitis. Ocul Immunol Inflamm. 2018;26(1):2-16.
Khan MA, Haroon M, Rosenbaum JT. Acute Anterior Uveitis and Spondyloarthritis: More Than Meets the Eye. Current Rheumatology Reports. 2015;17(9).
Whitcup SM. Anterior Uveitis. In: Nussenblatt RB, Whitcup SM, editors. Uveitis : fundamentals and clinical practice. 4 ed. United States of America: Elsevier; 2010. p. 251-63.
Torres S, Borges S, Artiles A. HLA-B27 and Clinical Features of Acute Anterior Uveitis in Cuba. Ocular Immunology and Inflammation. 2012;21(2):119-23.
Kopplin LJ, Mount G, Suhler EB. Review for Disease of the Year: Epidemiology of HLA-B27 Associated Ocular Disorders. Ocul Immunol Inflamm. 2016;24(4):470-5.
Zhang L, Zhang YJ, Chen J, Huang XL, Fang GS, Yang LJ, et al. The association of HLA-B27 and Klebsiella pneumoniae in ankylosing spondylitis: A systematic review. Microb Pathog. 2018;117:49-54.
Wakefield D, Yates W, Amjadi S, McCluskey P. HLA-B27 Anterior Uveitis: Immunology and Immunopathology. Ocul Immunol Inflamm. 2016;24(4):450-9.
Bowness P. Hla-B27. Annu Rev Immunol. 2015;33:29-48.
Abbas AK, Lichtman AH, Pillai S. Basic Immunology; Functions and Disorders of the Immune System. 5 ed. United States of America: Elsevier; 2016.
Oshima M, Deitiker PR, Jankovic J, Duane DD, Aoki KR, Atassi MZ. Human T-cell responses to botulinum neurotoxin: proliferative responses in vitro of lymphocytes from botulinum neurotoxin A-treated movement disorder patients. J Neuroimmunol. 2011;237(1-2):66-72.
Santos SG, Lynch S, Campbell EC, Antoniou AN, Powis SJ. Induction of HLA-B27 heavy chain homodimer formation after activation in dendritic cells. Arthritis Res Ther. 2008;10(4):R100.
Bowness P, Ridley A, Shaw J, Chan AT, Wong-Baeza I, Fleming M, et al. Th17 cells expressing KIR3DL2+ and responsive to HLA-B27 homodimers are increased in ankylosing spondylitis. J Immunol. 2011;186(4):2672-80.
van Tok MN, Satumtira N, Dorris M, Pots D, Slobodin G, van de Sande MG, et al. Innate Immune Activation Can Trigger Experimental Spondyloarthritis in HLA-B27/Hubeta2m Transgenic Rats. Front Immunol. 2017;8:920.
van Tok MN, Na S, Lao CR, Alvi M, Pots D, van de Sande MGH, et al. The Initiation, but Not the Persistence, of Experimental Spondyloarthritis Is Dependent on Interleukin-23 Signaling. Front Immunol. 2018;9:1550.
Wildner G, Diedrichs-Mohring M, Thurau SR. Induction of arthritis and uveitis in Lewis rats by antigenic mimicry of peptides from HLA-B27 and cytokeratin. Eur J Immunol. 2002;32(1):299-306.
Diedrichs-Mohring M, Wildner G. Immunostimulatory and immunomodulatory peptides derived from the alpha1 domain of HLA-B27 in experimental autoimmune diseases in Lewis rats. Immunobiology. 2005;209(10):711-7.
Tedeschi V, Vitulano C, Cauli A, Paladini F, Piga M, Mathieu A, et al. The Ankylosing Spondylitis-associated HLAB*2705 presents a B*0702-restricted EBV epitope and sustains the clonal amplification of cytotoxic T cells in patients. Mol Med. 2016;22:215-23.
Tedeschi V, Alba J, Paladini F, Paroli M, Cauli A, Mathieu A, et al. Unusual Placement of an EBV Epitope into the Groove of the Ankylosing Spondylitis-Associated HLA-B27 Allele Allows CD8+ T Cell Activation. Cells. 2019;8(6).
Kim YJ, Kim JH, Lee KJ, Choi MM, Kim YH, Rhie GE, et al. Botulinum neurotoxin type A induces TLR2-mediated inflammatory responses in macrophages. PLoS One. 2015;10(4):e0120840.
Oshima M, Deitiker P, Jankovic J, Atassi MZ. The Regions on the Light Chain of Botulinum Neurotoxin Type A Recognized by T Cells from Toxin-Treated Cervical Dystonia Patients. The Complete Human T-Cell Recognition Map of the Toxin Molecule. Immunol Invest. 2018;47(1):18-39.
Oshima M, Deitiker P, Jankovic J, Atassi MZ. Submolecular recognition regions of the HN domain of the heavy chain of botulinum neurotoxin type A by T cells from toxin-treated cervical dystonia patients. J Neuroimmunol. 2016;300:36-46.
Vlata Z, Tsatsakis A, Tzagournissakis M, Krambovitis E. Evaluation of specific immune responses to BoNT/A and tetanus toxoid in patients undergoing treatment for neurologic disorders. Endocr Metab Immune Disord Drug Targets. 2012;12(3):268-73.
Information NCFB. Basic Local Alignment Search Tool 2020 [cited 2020 June 15] Available from: blast.ncbi.nlm.nih.gov/.
Jurtz V, Paul S, Andreatta M, Marcatili P, Peters B, Nielsen M. NetMHCpan-4.0: Improved Peptide–MHC Class I Interaction Predictions Integrating Eluted Ligand and Peptide Binding Affinity Data. The Journal of Immunology,. 2017;199(9):3360-8.
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Licensing
Ninety Nine Publication publishes articles under the Creative Commons Attribution 4.0 International License (CC BY 4.0). This licensing allows for any use of the work, provided the original author(s) and source are credited, thereby facilitating the free exchange and use of research for the advancement of knowledge.
Detailed Licensing Terms
Attribution (BY): Users must give appropriate credit, provide a link to the license, and indicate if changes were made. Users may do so in any reasonable manner, but not in any way that suggests the licensor endorses them or their use.
No Additional Restrictions: Users may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.