T-cell reactivity to myelin proteolipid protein drives the development of brainstem and cerebellar lesions in multiple sclerosis

Pender, M. P., Csurhes, P. A. and Greer, J. M. (2006). T-cell reactivity to myelin proteolipid protein drives the development of brainstem and cerebellar lesions in multiple sclerosis. In: 8th International Conference on Neuroimmunology, Nagoya, Japan, (78-79). 15-19 October 2006. doi:10.1016/j.jneuroim.2006.07.002


Author Pender, M. P.
Csurhes, P. A.
Greer, J. M.
Title of paper T-cell reactivity to myelin proteolipid protein drives the development of brainstem and cerebellar lesions in multiple sclerosis
Conference name 8th International Conference on Neuroimmunology
Conference location Nagoya, Japan
Conference dates 15-19 October 2006
Journal name Journal of Neuroimmunology   Check publisher's open access policy
Place of Publication Amsterdam, Netherlands
Publisher Elsevier BV
Publication Year 2006
Year available 2006
Sub-type Published abstract
DOI 10.1016/j.jneuroim.2006.07.002
ISSN 0165-5728
1872-8421
0169-5088
Volume 178
Issue Supplement 1
Start page 78
End page 79
Total pages 2
Language eng
Abstract/Summary The mechanisms responsible for the localization of lesions in multiple sclerosis (MS) are currently unknown. To investigate this, we performed HLA-DR and HLA-DQ typing and examined T-cell reactivity to myelin proteins in 121 patients with MS not on immunomodulatory therapy, 71 healthy subjects and 47 patients with other diseases of the central nervous system (CNS). We found that 47.0% of MS patients with brainstem or cerebellar lesions, as determined by clinical assessment and/or magnetic resonance imaging, had increased circulating T-cell reactivity to an immunodominant region of myelin proteolipid protein (PLP184–209), compared to 10.0% of MS patients without brainstem or cerebellar lesions, 11.3% of healthy subjects and 19.1% of patients with other CNS diseases (p<0.0006). We also found that 78.6% of MS patients with brainstem or cerebellar lesions carried HLA-DR4, DR7 or DR13 alleles, whereas only 28.9% of patients without brainstem or cerebellar lesions carried these alleles (p=0.00000003). Furthermore, 60.9% of MS patients carrying HLA-DR4, DR7 or DR13 alleles had increased T-cell reactivity to PLP184–209, compared to 12.2% of MS patients not carrying these HLA alleles p=0.0001). Interestingly, H-2k mice immunized with PLP184–209 also develop inflammatory demyelinating lesions predominantly in the brainstem and cerebellum. Our results indicate that T-cell reactivity to PLP184–209 drives the development of brainstem and cerebellar lesions in MS. In patients carrying HLA-DR4, DR7 or DR13 alleles, therapy with altered peptide ligands based on PLP184–209 might prevent the development of brainstem and cerebellar lesions.
Subjects 320207 Autoimmunity
300504 Immunology
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Conference Paper
Collection: School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Google Scholar Search Google Scholar
Created: Thu, 03 Feb 2011, 12:51:58 EST by Mr Peter Csurhes on behalf of Medicine - Royal Brisbane and Women's Hospital