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Institute
  • Neurology Unit
  • Research Theme Beyond the Neuron
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    Dr Joanne Jones

    University Position
    Clinical Fellow

    Interests

    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.

    Key Publications

    Autoimmunity and long-term safety and efficacy of alemtuzumab for multiple sclerosis: Benefit/risk following review of trial and post-marketing data.

    DOI: http://doi.org/10.1177/13524585211061335
    Journal: Mult Scler
    E-pub date: 1 Apr 2022
    Authors: AJ Coles, JL Jones, P Vermersch, A Traboulsee, AD Bass, A Boster, A Chan, G Comi, Ó Fernández, G Giovannoni, E Kubala Havrdova, C LaGanke, X Montalban, C Oreja-Guevara, F Piehl, H Wiendl, T Ziemssen

    Safety and efficacy of bexarotene in patients with relapsing-remitting multiple sclerosis (CCMR One): a randomised, double-blind, placebo-controlled, parallel-group, phase 2a study.

    DOI: http://doi.org/10.1016/S1474-4422(21)00179-4
    Journal: Lancet Neurol
    E-pub date: 1 Sep 2021
    Authors: JWL Brown, NG Cunniffe, F Prados, B Kanber, JL Jones, E Needham, Z Georgieva, D Rog, OR Pearson, J Overell, D MacManus, RS Samson, J Stutters, C Ffrench-Constant, CAM Gandini Wheeler-Kingshott, C Moran, PD Flynn, AW Michell, RJM Franklin, S Chandran, DR Altmann, DT Chard, P Connick, AJ Coles

    The MS Remyelinating Drug Bexarotene (an RXR Agonist) Promotes Induction of Human Tregs and Suppresses Th17 Differentiation In Vitro.

    DOI: http://doi.org/10.3389/fimmu.2021.712241
    Journal: Front Immunol
    E-pub date: 1 Aug 2021
    Authors: CM Gaunt, DB Rainbow, RJ Mackenzie, LB Jarvis, HS Mousa, N Cunniffe, Z Georgieva, JW Brown, AJ Coles, JL Jones

    Periventricular magnetisation transfer ratio abnormalities in multiple sclerosis improve after alemtuzumab.

    DOI: http://doi.org/10.1177/1352458519852093
    Journal: Mult Scler
    E-pub date: 31 Aug 2020
    Authors: JWL Brown, F Prados Carrasco, A Eshaghi, CH Sudre, T Button, M Pardini, RS Samson, S Ourselin, CAG Wheeler-Kingshott, JL Jones, AJ Coles, DT Chard

    Peripheral innate immune and bacterial signals relate to clinical heterogeneity in Parkinson’s disease.

    DOI: http://doi.org/10.1016/j.bbi.2020.01.018
    Journal: Brain Behav Immun
    E-pub date: 1 Jul 2020
    Authors: RS Wijeyekoon, D Kronenberg-Versteeg, KM Scott, S Hayat, W-L Kuan, JR Evans, DP Breen, G Cummins, JL Jones, MR Clatworthy, RA Floto, RA Barker, CH Williams-Gray

    Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis.

    DOI: http://doi.org/10.1001/jama.2018.20588
    Journal: JAMA
    E-pub date: 15 Jan 2019
    Authors: JWL Brown, A Coles, D Horakova, E Havrdova, G Izquierdo, A Prat, M Girard, P Duquette, M Trojano, A Lugaresi, R Bergamaschi, P Grammond, R Alroughani, R Hupperts, P McCombe, V Van Pesch, P Sola, D Ferraro, F Grand'Maison, M Terzi, J Lechner-Scott, S Flechter, M Slee, V Shaygannejad, E Pucci, F Granella, V Jokubaitis, M Willis, C Rice, N Scolding, A Wilkins, OR Pearson, T Ziemssen, M Hutchinson, K Harding, J Jones, C McGuigan, H Butzkueven, T Kalincik, N Robertson, MSBase Study Group

    Monocyte Function in Parkinson’s Disease and the Impact of Autologous Serum on Phagocytosis.

    DOI: http://doi.org/10.3389/fneur.2018.00870
    Journal: Front Neurol
    E-pub date: 1 Aug 2018
    Authors: RS Wijeyekoon, D Kronenberg-Versteeg, KM Scott, S Hayat, JL Jones, MR Clatworthy, RA Floto, RA Barker, CH Williams-Gray

    Alemtuzumab-Induced Thyroid Dysfunction Exhibits Distinctive Clinical and Immunological Features.

    DOI: http://doi.org/10.1210/jc.2018-00359
    Journal: J Clin Endocrinol Metab
    E-pub date: 1 Aug 2018
    Authors: N Pariani, M Willis, I Muller, S Healy, T Nasser, A McGowan, G Lyons, J Jones, K Chatterjee, C Dayan, N Robertson, A Coles, C Moran

    Abnormalities of age-related T cell senescence in Parkinson’s disease.

    DOI: http://doi.org/10.1186/s12974-018-1206-5
    Journal: J Neuroinflammation
    E-pub date: 28 May 2018
    Authors: CH Williams-Gray, RS Wijeyekoon, KM Scott, S Hayat, RA Barker, JL Jones

    Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2.

    DOI: http://doi.org/10.1172/jci.insight.93739
    Journal: JCI Insight
    E-pub date: 17 Aug 2017
    Authors: ML Pekalski, AR García, RC Ferreira, DB Rainbow, DJ Smyth, M Mashar, J Brady, N Savinykh, XC Dopico, S Mahmood, S Duley, HE Stevens, NM Walker, AJ Cutler, F Waldron-Lynch, DB Dunger, C Shannon-Lowe, AJ Coles, JL Jones, C Wallace, JA Todd, LS Wicker

    A novel strategy to reduce the immunogenicity of biological therapies.

    DOI: http://doi.org/10.4049/jimmunol.1000422
    Journal: J Immunol
    E-pub date: 1 Jul 2010
    Authors: J Somerfield, GA Hill-Cawthorne, A Lin, MS Zandi, C McCarthy, JL Jones, M Willcox, D Shaw, SAJ Thompson, AS Compston, G Hale, H Waldmann, AJ Coles

    IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H).

    DOI: http://doi.org/10.1172/JCI37878
    Journal: J Clin Invest
    E-pub date: 1 Jul 2009
    Authors: JL Jones, C-L Phuah, AL Cox, SA Thompson, M Ban, J Shawcross, A Walton, SJ Sawcer, A Compston, AJ Coles

    Alemtuzumab vs. interferon beta-1a in early multiple sclerosis.

    DOI: http://doi.org/10.1056/NEJMoa0802670
    Journal: N Engl J Med
    E-pub date: 23 Oct 2008
    Authors: CAMMS223 Trial Investigators, AJ Coles, DAS Compston, KW Selmaj, SL Lake, S Moran, DH Margolin, K Norris, PK Tandon

    Publications

    Remyelination varies between and within lesions in multiple sclerosis following bexarotene.

    DOI: http://doi.org/10.1002/acn3.51662
    Journal: Ann Clin Transl Neurol
    E-pub date: 1 Oct 2022
    Authors: JWL Brown, F Prados, DR Altmann, B Kanber, J Stutters, NG Cunniffe, JL Jones, ZG Georgieva, EJ Needham, C Daruwalla, CG Wheeler-Kingshott, P Connick, S Chandran, R Franklin, D MacManus, R Samson, A Coles, D Chard

    Therapeutically expanded human regulatory T-cells are super-suppressive due to HIF1A induced expression of CD73.

    DOI: http://doi.org/10.1038/s42003-021-02721-x
    Journal: Commun Biol
    E-pub date: 14 Oct 2021
    Authors: LB Jarvis, DB Rainbow, V Coppard, SK Howlett, Z Georgieva, JL Davies, HK Mullay, J Hester, T Ashmore, A Van Den Bosch, JT Grist, AJ Coles, HS Mousa, S Pluchino, KT Mahbubani, JL Griffin, K Saeb-Parsy, F Issa, L Peruzzotti-Jametti, LS Wicker, JL Jones

    The MS remyelinating drug bexarotene (an RXR agonist) promotes induction of human Tregs and suppresses Th17 differentiation in vitro

    DOI: http://doi.org/10.1101/2021.02.17.431344
    Journal:
    E-pub date: 1 Aug 2021
    Authors: C Gaunt, D Rainbow, R Mackenzie, L Jarvis, H Mousa, N Cunniffe, Z Georgieva, W Brown, A Coles, J Jones

    Therapeutically expanded human regulatory T-cells are super- suppressive due to HIF1A induced expression of CD73.

    DOI: http://doi.org/10.21203/rs.3.rs-92789/v1
    Journal:
    E-pub date: 2 Mar 2021
    Authors: L Jarvis, D Rainbow, V Coppard, S Howlett, J Davies, H Mullay, J Hester, T Ashmore, AVD Bosch, J Grist, A Coles, H Mousa, S Pluchino, K Mahbubani, J Griffin, K Saeb-Parsy, F Issa, L Peruzzotti-Jametti, L Wicker, J Jones

    Neuroanatomical substrates of generalized brain dysfunction in COVID-19.

    DOI: http://doi.org/10.1007/s00134-020-06241-w
    Journal: Intensive Care Med
    E-pub date: 1 Jan 2021
    Authors: VFJ Newcombe, LRB Spindler, T Das, S Winzeck, K Allinson, EA Stamatakis, DK Menon, Cambridge NeuroCovid Imaging Collaborators

    Keratinocyte growth factor impairs human thymic recovery from lymphopenia.

    DOI: http://doi.org/10.1172/jci.insight.125377
    Journal: JCI Insight
    E-pub date: 7 May 2019
    Authors: AJ Coles, L Azzopardi, O Kousin-Ezewu, HK Mullay, SA Thompson, L Jarvis, J Davies, S Howlett, D Rainbow, J Babar, TJ Sadler, JWL Brown, E Needham, K May, ZG Georgieva, AE Handel, S Maio, M Deadman, I Rota, G Holländer, S Dawson, D Jayne, R Seggewiss-Bernhardt, DC Douek, JD Isaacs, JL Jones

    A case of anaphylaxis to alemtuzumab.

    DOI: http://doi.org/10.1007/s00415-019-09214-2
    Journal: J Neurol
    E-pub date: 1 Mar 2019
    Authors: CJS Nye, A Wagner, O Kousin-Ezewu, JL Jones, AJ Coles

    Hemophagocytic Lymphohistiocytosis in 2 Patients with Multiple Sclerosis Treated With Alemtuzumab

    DOI: http://doi.org/10.1212/WNL.0000000000005420
    Journal: Neurology
    E-pub date: 1 May 2018
    Authors: M Saarela, K Senthil, JL Jones, P Tienari, M Soilu-hanninen, L Airas, A Coles, J Saarinen

    Imaging intralesional heterogeneity of sodium concentration in multiple sclerosis: Initial evidence from 23Na-MRI.

    DOI: http://doi.org/10.1016/j.jns.2018.01.027
    Journal: J Neurol Sci
    E-pub date: 15 Apr 2018
    Authors: JT Grist, F Riemer, MA McLean, T Matys, F Zaccagna, SF Hilborne, JP Mason, I Patterson, R Slough, J Kaggie, SS Deen, MJ Graves, JL Jones, AJ Coles, FA Gallagher

    Alemtuzumab use in neuromyelitis optica spectrum disorders: a brief case series.

    DOI: http://doi.org/10.1007/s00415-015-7925-y
    Journal: JOURNAL OF NEUROLOGY
    E-pub date: 1 Aug 2016
    Authors: L Azzopardi, AL Cox, CL McCarthy, JL Jones, AJ Coles

    Predicting autoimmunity after alemtuzumab treatment of multiple sclerosis.

    DOI: http://doi.org/10.1136/jnnp-2013-307042
    Journal: J Neurol Neurosurg Psychiatry
    E-pub date: 1 Jul 2014
    Authors: L Azzopardi, SAJ Thompson, KE Harding, M Cossburn, N Robertson, A Compston, AJ Coles, JL Jones

    Accelerated lymphocyte recovery after alemtuzumab does not predict multiple sclerosis activity.

    DOI: http://doi.org/10.1212/WNL.0000000000000520
    Journal: Neurology
    E-pub date: 17 Jun 2014
    Authors: O Kousin-Ezewu, L Azzopardi, RA Parker, O Tuohy, A Compston, A Coles, J Jones

    Human autoimmunity after lymphocyte depletion is caused by homeostatic T-cell proliferation.

    DOI: http://doi.org/10.1073/pnas.1313654110
    Journal: Proc Natl Acad Sci U S A
    E-pub date: 10 Dec 2013
    Authors: JL Jones, SAJ Thompson, P Loh, JL Davies, OC Tuohy, AJ Curry, L Azzopardi, G Hill-Cawthorne, MT Fahey, A Compston, AJ Coles

    First use of alemtuzumab in Balo’s concentric sclerosis: a case report.

    DOI: http://doi.org/10.1177/1352458513498129
    Journal: Mult Scler
    E-pub date: 1 Oct 2013
    Authors: JWL Brown, AJ Coles, JL Jones

    Immune competence after alemtuzumab treatment of multiple sclerosis.

    DOI: http://doi.org/10.1212/WNL.0b013e3182a35215
    Journal: Neurology
    E-pub date: 3 Sep 2013
    Authors: CL McCarthy, O Tuohy, DAS Compston, DS Kumararatne, AJ Coles, JL Jones

    Autoimmune disease after alemtuzumab treatment for multiple sclerosis in a multicenter cohort.

    DOI: http://doi.org/10.1212/WNL.0b013e318228bec5
    Journal: Neurology
    E-pub date: 9 Aug 2011
    Authors: M Cossburn, AA Pace, J Jones, R Ali, G Ingram, K Baker, C Hirst, J Zajicek, N Scolding, M Boggild, T Pickersgill, Y Ben-Shlomo, A Coles, NP Robertson

    Predicting Autoimmunity Following Treatment of Multiple Sclerosis with Alemtuzumab

    DOI: http://doi.org/10.1016/j.clim.2010.03.310
    Journal: CLINICAL IMMUNOLOGY
    E-pub date: 1 Aug 2010
    Authors: J Jones, A Compston, A Coles