Research
We study human autoimmunity; in particular we aim to understand why autoimmunity often occurs during recovery from T cell lymphopenia.
People with multiple sclerosis, treated with the highly effective lymphocyte depleting antibody alemtuzumab offer a rare opportunity to study this phenomenon directly in humans, as 1 in 3 patients develop a new autoimmune disease after treatment (mainly thyroid). Using this “human model” we have shown that rebound T cell reconstitution via the proliferation of cells that have escaped depletion is antagonistic to tolerance. We now ask:
1) Can autoimmunity after alemtuzumab be reduced by promoting T cell production via the thymus? In collaboration with Alasdair Coles, we are testing this approach in an MRC-funded trial (CAMTHY).
2) Why do regulatory T cells (which expand more rapidly than non-Tregs) fail to prevent reconstitution associated autoimmunity? This question forms the basis of a Wellcome-Trust funded project.
Publications
Accelerated lymphocyte recovery after alemtuzumab therapy for multiple sclerosis does not predict disease activity. Onajite Kousin-Ezewu, Laura Azzopardi, Richard A. Parker, Orla Tuohy, Alastair Compston, Alasdair Coles, Joanne Jones. Neurology. 2014 May 16.
Human autoimmunity after lymphocyte depletion is due to homeostatic T-cell proliferation. J. L. Jones, S. A. J. Thompson, P. Loh, J. L. Davies, O. C. Tuohy, A. J. Curry, L. Azzopardi, G. Hill-Cawthorne, M. T. Fahey, D. A. S. Compston, A. J. Coles. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20200-5.
Predicting autoimmunity after alemtuzumab treatment of multiple sclerosis. Azzopardi L, Thompson SA, Harding KE, Cossburn M, Robertson N, Compston A, Coles AJ, Jones JL. J Neurol Neurosurg Psychiatry. 2013 Dec 24.
Immune competence after alemtuzumab treatment of multiple sclerosis. McCarthy CL, Tuohy O, Compston DAS, Kumararatne DS, Coles AJ, Jones JL. Neurology. 2013 Sep 3;81(10):872-6.
Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity. Joanne L. Jones, Jane M. Anderson, Chia-Ling Phuah, Edward J. Fox, Krzysztof Selmaj, David Margolin, Stephen Lake, Alastair Wilkins, Daniel J. Webber, Alastair Compston, and Alasdair J. Coles. Brain. 2010 Aug; 133 (Pt 8):2232-47.
Serum IL-21 predicts the development of autoimmunity in humans following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H). Jones JL, Phuah CL, Cox AL, Thompson SJ, Shawcross J, Ban Ms, Walton A, Sawcer SJ, Compston DAS, Coles AJ. J Clin Invest. 2009 Jul;119(7):2052-61.
Alemtuzumab versus Interferon beta-1a in Early, Relapsing-Remitting Multiple Sclerosis. International CAMMS-223 Trial Study Group. N Engl J Med. 2008 Oct 23; 359(17):1786-801.
Clinical relevance of serum antibodies to extracellular N-methyl-d-aspartate receptor epitopes. Zandi MS, Paterson RW, Ellul MA, Jacobson L, Al-Diwani A, Jones JL, Cox AL, Lennox B, Stamelou M, Bhatia KP, Scott JM, Coles AJ, Kullmann DM, Vincent A. J. Neurol Neurosurg Psychiatry. 2014 Sep 22.
Alemtuzumab treatment of multiple sclerosis: long-term safety and efficacy. Tuohy O, Costelloe L, Hill-Cawthorne G, Bjornson I, Harding K, Robertson N, May K, Button T, Azzopardi L,Kousin-Ezewu O, Jones J, Compston DA, Coles A. J Neurol Neurosurg Psychiatry. 2014 May 21.
Mode of action and clinical studies with alemtuzumab. Jones JL, Coles AJ. Exp.Neurol. 2014 May 2.
Exome sequencing in single cells from the cerebrospinal fluid in multiple sclerosis. A Kemppinen, A Baker, W Liao, B Fiddes, J Jones, A Compston, M Ban, S Sawcer. Journal of Multiple Sclerosis 2014 April 16
Non-myeloablative autologous stem cell transplantation modifies immune balance in multiple sclerosis . Sofia V. Abrahamsson, Daniela Angelini, Amy N. Dubinsky, Esther Morel, Unsong Oh, Joanne Jones, Daniele Carassiti, Richard Reynolds, Marco Salvetti, Peter Calabresi, Alasdair Coles, Luca Battistini, Roland Martin, Richard K. Burt, and Paolo A. Muraro. Brain. 2013 Sep;136(Pt 9):2888-903.
First use of alemtuzumab in Balo's concentric sclerosis. Brown W, Coles AJ, and Jones JL. Mult Scler. 2013 Oct;19(12):1673-5.
Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis. Grant A Hill-Cawthorne, Tom Button, Orla Tuohy, Joanne L Jones, Karen May, Jennifer Somerfield, Alison Green, Gavin Giovannoni, D Alastair S Compston, Michael T Fahey and Alasdair J Coles. J. Neurol Neurosurg Psychiatry. 2012 Mar; 83(3):298-304.
Secondary autoimmune diseases following alemtuzumab therapy for multiple sclerosis. Costelloe L, Jones J, Coles A. Expert Rev Neurotherapy 2012 Mar 12(3): 335-41.
Radiologically compatible CLIPPERS may conceal a number of pathologies. Jones JL, Dean AF, Antoun N, Scoffings DJ, Burnet NG, Coles AJ. Brain. 2011 Aug; 134(Pt 8):e187
Autoimmune disease after alemtuzumab treatment for multiple sclerosis in a multicenter cohort. Cossburn M, Pace AA, Jones JL, Ali R, Ingram G, Baker K, Hirst C, Zajicek J, Scolding N, Boggild M, Pickersgill T, Ben-Shlomo Y, Coles A, Robertson NP. Neurology 2011 Aug 9; 77(6):573-9
New treatment strategies in multiple sclerosis Jones JL, Coles AJ. Exp.Neurol. 2010 Sep;225(1):34-9.
B-cell reconstitution and BAFF after alemtuzumab (Campath-1H) treatment of multiple sclerosis. Thompson SA, Jones JL, Cox AL, Compston DA, Coles AJ. J Clin Immunol, 2010 Jan; 30 (1): 99-105.
Alemtuzumab in the treatment of IVIG-dependent chronic inflammatory demyelinating polyneuropathy. Marsh EA, Hirst CL, Llewelyn JG, Cossburn MD, Reilly MM, Krishnan A, Doran M, Ryan AM, Coles AJ, Jones JL, Robertson NP. J Neurol. 2010 Jun; 257(6):913-9.
A novel strategy to reduce the immunogenicity of biological therapies. Somerfield J, Hill-Cawthorne GA, Lin A, Zandi MS, McCarthy C, Jones JL, Wilcox M, Shaw D, Thompson SA, Compston AS, Hale G, Waldmann H, Coles AJ. J.Immunol. 2010 Jul 1; 185(1):763-8.
Spotlight on Alemtuzumab. Jones JL, Coles AJ. International Journal of MS 2009 Sep;16(3):77-81
Campath-1H Treatment of Multiple Sclerosis. Jones JL, Coles AJ. Neurodegenerative Diseases. 2008; 5:27-31
The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy in relapsing-remitting and secondary progressive disease. Coles AJ, Cox A, Le Page E, Jones JL, Trip SA, Deans J, Seaman S, Miller DH, Hale G, Waldmann H, Compston DA: 2006: J Neurol. 2006 Jan;253(1):98-108.
The basics of Microarrays. Jones JL. Advances in Clinical Neuroscience. 2006; 6(1): 29-31.
Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Cox A, Thompson SA, JonesJL, Robertson VH, Hale G, Waldmann H, Compston DA, Coles AJ. European Journal of Immunology, 2005; 35:3332-42.
