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Published in: BMC Neurology 1/2015

Open Access 01-12-2015 | Research article

MS in South Asians in England: early disease onset and novel pattern of myelin autoimmunity

Authors: Richard S Nicholas, Vassiliki Kostadima, Maya Hanspal, Benjamin R Wakerley, Ruhena Sergeant, Saskia Decuypere, Omar Malik, Rosemary J Boyton, Daniel M Altmann

Published in: BMC Neurology | Issue 1/2015

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Abstract

Background

Epidemiological studies describe a latitude gradient for increased MS prevalence and a preponderance of disease in Caucasian individuals. However, individuals from other ethnic backgrounds and low-risk regions can acquire a raised risk through migration. Nearly a fifth of the London population is of Asian/Asian-British origin and a significant proportion of referrals are from this group.

Methods

We investigated whether there were differences in timing, presentation, severity, and immunology of disease (with respect to CD4 myelin epitope recognition) between individuals in London with MS who were either of S. Asian or Caucasian origin. Individuals of S. Asian origin with MS were compared with healthy S. Asian controls, individuals with MS and of Caucasian origin and Caucasian controls.

Results

Age at MS onset is significantly lower in the S. Asian group, attributable to earlier onset specifically in UK-born individuals, though clinical presentation is similar. Analysis of CD4 autoimmunity to myelin antigens shows disease in S. Asian individuals to encompass recognition of novel epitopes; immunity to MBP116-130 in S. Asian individuals was highly disease-specific.

Conclusions

These findings emphasize the need to define disease profiles across ethnicities and identify environmental triggers conferring acquired risk. Such findings must inform choices for immunotherapeutic interventions suitable for all, across ethnicities.
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Literature
1.
2.
go back to reference Quintana FJ, Farez MF, Izquierdo G, Lucas M, Cohen IR, Weiner HL. Antigen microarrays identify CNS-produced autoantibodies in RRMS. Neurology. 2012;78:532–9.CrossRefPubMedPubMedCentral Quintana FJ, Farez MF, Izquierdo G, Lucas M, Cohen IR, Weiner HL. Antigen microarrays identify CNS-produced autoantibodies in RRMS. Neurology. 2012;78:532–9.CrossRefPubMedPubMedCentral
3.
go back to reference Hafler DA, Slavik JM, Anderson DE, O’Connor KC, De Jager P, Baecher-Allan C. Multiple sclerosis. Immunol Rev. 2005;204:208–31.CrossRefPubMed Hafler DA, Slavik JM, Anderson DE, O’Connor KC, De Jager P, Baecher-Allan C. Multiple sclerosis. Immunol Rev. 2005;204:208–31.CrossRefPubMed
4.
5.
go back to reference International MS Genetics Consortium. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011;476(7359):214–9.CrossRef International MS Genetics Consortium. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011;476(7359):214–9.CrossRef
6.
go back to reference International MS Genetics Consortium. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013;45:1353–60.CrossRef International MS Genetics Consortium. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013;45:1353–60.CrossRef
7.
go back to reference GAMES. Transatlantic multiple sclerosis genetics cooperative. A meta-analysis of whole genome linkage screens in multiple sclerosis. J Neuroimmunol. 2003;143:39–46.CrossRef GAMES. Transatlantic multiple sclerosis genetics cooperative. A meta-analysis of whole genome linkage screens in multiple sclerosis. J Neuroimmunol. 2003;143:39–46.CrossRef
8.
go back to reference Kankonkar S, Jeyanti G, Singhal BS, Shankarkumar U. Evidence for novel DRB1*15 allele association among clinically definite multiple sclerosis patients from Mumbai, India. Hum Immunol. 2003;64:478–82.CrossRefPubMed Kankonkar S, Jeyanti G, Singhal BS, Shankarkumar U. Evidence for novel DRB1*15 allele association among clinically definite multiple sclerosis patients from Mumbai, India. Hum Immunol. 2003;64:478–82.CrossRefPubMed
10.
go back to reference Pandit L. Insights into the changing perspectives of Multiple Sclerosis in India. Autoimmune Dis. 2011:937586. doi: 10.4061/2011/937586. Pandit L. Insights into the changing perspectives of Multiple Sclerosis in India. Autoimmune Dis. 2011:937586. doi: 10.4061/2011/937586.
11.
go back to reference Wadia NH, Bhatia K. Multiple sclerosis is prevalent in the Zoroastrians (Parsis) of India. Ann Neurol. 1990;28:177–9.CrossRefPubMed Wadia NH, Bhatia K. Multiple sclerosis is prevalent in the Zoroastrians (Parsis) of India. Ann Neurol. 1990;28:177–9.CrossRefPubMed
12.
go back to reference Bansil S, Singhal BS, Ahuja GK, Ladiwala U, Behari M, Friede R, et al. Comparison between multiple sclerosis in India and the United States: a case–control study. Neurology. 1996;46:385–7.CrossRefPubMed Bansil S, Singhal BS, Ahuja GK, Ladiwala U, Behari M, Friede R, et al. Comparison between multiple sclerosis in India and the United States: a case–control study. Neurology. 1996;46:385–7.CrossRefPubMed
13.
go back to reference Shibasaki H, McDonald WI, Kuroiwa Y. Racial modification of clinical picture of multiple sclerosis: comparison between British and Japanese patients. J Neurol Sci. 1981;49:253–71.CrossRefPubMed Shibasaki H, McDonald WI, Kuroiwa Y. Racial modification of clinical picture of multiple sclerosis: comparison between British and Japanese patients. J Neurol Sci. 1981;49:253–71.CrossRefPubMed
14.
go back to reference Pandit L, Ban M, Sawcer S, Singhal B, et al. Evaluation of the established non-MHC multiple sclerosis loci in an Indian population. Mult Scler. 2011;17:139–43.CrossRefPubMed Pandit L, Ban M, Sawcer S, Singhal B, et al. Evaluation of the established non-MHC multiple sclerosis loci in an Indian population. Mult Scler. 2011;17:139–43.CrossRefPubMed
15.
go back to reference Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors. Ann Neurol. 2007;61:504–13.CrossRefPubMed Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors. Ann Neurol. 2007;61:504–13.CrossRefPubMed
16.
go back to reference Handel AE, Giovannoni G, Ebers GC, Ramagopalan SV. Environmental factors and their timing in adult-onset multiple sclerosis. Nat Rev Neurol. 2010;6:156–66.CrossRefPubMed Handel AE, Giovannoni G, Ebers GC, Ramagopalan SV. Environmental factors and their timing in adult-onset multiple sclerosis. Nat Rev Neurol. 2010;6:156–66.CrossRefPubMed
17.
go back to reference Dean G, Elian M. Age at immigration to England of Asian and Caribbean immigrants and the risk of developing multiple sclerosis. J Neurol Neurosurg Psychiatry. 1997;63:565–8.CrossRefPubMedPubMedCentral Dean G, Elian M. Age at immigration to England of Asian and Caribbean immigrants and the risk of developing multiple sclerosis. J Neurol Neurosurg Psychiatry. 1997;63:565–8.CrossRefPubMedPubMedCentral
18.
go back to reference Kurtzke JF, Delasnerie-Lauprêtre N, Wallin MT. Multiple sclerosis in North African migrants to France. Acta Neurol Scand. 1998;98:302–9.CrossRefPubMed Kurtzke JF, Delasnerie-Lauprêtre N, Wallin MT. Multiple sclerosis in North African migrants to France. Acta Neurol Scand. 1998;98:302–9.CrossRefPubMed
19.
go back to reference Cree BA, Reich DE, Khan O, De Jager PL, Nakashima I, Takahashi T, et al. Modification of multiple sclerosis phenotypes by African ancestry at HLA. Arch Neurol. 2009;66:226–33.CrossRefPubMedPubMedCentral Cree BA, Reich DE, Khan O, De Jager PL, Nakashima I, Takahashi T, et al. Modification of multiple sclerosis phenotypes by African ancestry at HLA. Arch Neurol. 2009;66:226–33.CrossRefPubMedPubMedCentral
20.
go back to reference Isobe N, Gourraud PA, Harbo HF, Caillier SJ, Santaniello A, Khankhanian P, et al. Genetic risk variants in African Americans with multiple sclerosis. Neurology. 2013;8:219–27.CrossRef Isobe N, Gourraud PA, Harbo HF, Caillier SJ, Santaniello A, Khankhanian P, et al. Genetic risk variants in African Americans with multiple sclerosis. Neurology. 2013;8:219–27.CrossRef
21.
go back to reference Roxburgh RH, Seaman SR, Masterman T, Hensiek AE, et al. Multiple sclerosis severity score: using disability and disease duration to rate disease severity. Neurology. 2005;64:1144–51.CrossRefPubMed Roxburgh RH, Seaman SR, Masterman T, Hensiek AE, et al. Multiple sclerosis severity score: using disability and disease duration to rate disease severity. Neurology. 2005;64:1144–51.CrossRefPubMed
22.
go back to reference McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121–7.CrossRefPubMed McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121–7.CrossRefPubMed
23.
go back to reference Yonkers NL, Rodriguez B, Post AB, Asaad R, Jones L, Lederman MM, et al. HIV coinfection impairs CD28-mediated costimulation of hepatitis C virus-specific CD8 cells. J Infect Dis. 2006;194(3):391–400.CrossRefPubMed Yonkers NL, Rodriguez B, Post AB, Asaad R, Jones L, Lederman MM, et al. HIV coinfection impairs CD28-mediated costimulation of hepatitis C virus-specific CD8 cells. J Infect Dis. 2006;194(3):391–400.CrossRefPubMed
24.
go back to reference Perz JB, Szydlo R, Sergeant R, Sanz J, O'Shea D, Khan T, et al. Impact of HLA class I and class II DNA high-resolution HLA typing on clinical outcome in adult unrelated stem cell transplantation after in vivo T-cell depletion with alemtuzumab. Transpl Immunol. 2007;182:179–85.CrossRef Perz JB, Szydlo R, Sergeant R, Sanz J, O'Shea D, Khan T, et al. Impact of HLA class I and class II DNA high-resolution HLA typing on clinical outcome in adult unrelated stem cell transplantation after in vivo T-cell depletion with alemtuzumab. Transpl Immunol. 2007;182:179–85.CrossRef
25.
go back to reference Goebels N, Hofstetter H, Schmidt S, Brunner C, Wekerle H, Hohlfeld R. Repertoire dynamics of autoreactive T cells in multiple sclerosis patients and healthy subjects: epitope spreading versus clonal persistence. Brain. 2000;123(Pt 3):508–18.CrossRefPubMed Goebels N, Hofstetter H, Schmidt S, Brunner C, Wekerle H, Hohlfeld R. Repertoire dynamics of autoreactive T cells in multiple sclerosis patients and healthy subjects: epitope spreading versus clonal persistence. Brain. 2000;123(Pt 3):508–18.CrossRefPubMed
26.
go back to reference Meinl E, Weber F, Drexler K, Morelle C, Ott M, Saruhan-Direskeneli G, et al. Myelin basic protein-specific T lymphocyte repertoire in multiple sclerosis. Complexity of the response and dominance of nested epitopes due to recruitment of multiple T cell clones. J Clin Invest. 1993;92:2633–43.CrossRefPubMedPubMedCentral Meinl E, Weber F, Drexler K, Morelle C, Ott M, Saruhan-Direskeneli G, et al. Myelin basic protein-specific T lymphocyte repertoire in multiple sclerosis. Complexity of the response and dominance of nested epitopes due to recruitment of multiple T cell clones. J Clin Invest. 1993;92:2633–43.CrossRefPubMedPubMedCentral
27.
go back to reference Pender MP, Csurhes PA, Greer JM, Mowat PD, Henderson RD, Cameron KD, et al. Surges of increased T cell reactivity to an encephalitogenic region of myelin proteolipid protein occur more often in patients with multiple sclerosis than in healthy subjects. J Immunol. 2000;16:5322–31.CrossRef Pender MP, Csurhes PA, Greer JM, Mowat PD, Henderson RD, Cameron KD, et al. Surges of increased T cell reactivity to an encephalitogenic region of myelin proteolipid protein occur more often in patients with multiple sclerosis than in healthy subjects. J Immunol. 2000;16:5322–31.CrossRef
28.
go back to reference Muraro PA, Cassiani-Ingoni R, Chung K, Packer AN, Sospedra M, Martin R. Clonotypic analysis of cerebrospinal fluid T cells during disease exacerbation and remission in a patient with multiple sclerosis. J Neuroimmunol. 2006;171(1–2):177–83.CrossRefPubMed Muraro PA, Cassiani-Ingoni R, Chung K, Packer AN, Sospedra M, Martin R. Clonotypic analysis of cerebrospinal fluid T cells during disease exacerbation and remission in a patient with multiple sclerosis. J Neuroimmunol. 2006;171(1–2):177–83.CrossRefPubMed
29.
go back to reference Lutterotti A, Yousef S, Sputtek A, Stürner KH, Stellmann JP, Breiden P. Antigen-specific tolerance by autologous myelin peptide-coupled cells: a phase 1 trial in multiple sclerosis. Sci Transl Med. 2013;5(188):188ra75.CrossRefPubMedPubMedCentral Lutterotti A, Yousef S, Sputtek A, Stürner KH, Stellmann JP, Breiden P. Antigen-specific tolerance by autologous myelin peptide-coupled cells: a phase 1 trial in multiple sclerosis. Sci Transl Med. 2013;5(188):188ra75.CrossRefPubMedPubMedCentral
30.
go back to reference Minohara M, Ochi H, Matsushita S, Irie A, Nishimura Y, Kira J. Differences between T-cell reactivities to major myelin protein-derived peptides in opticospinal and conventional forms of multiple sclerosis and healthy controls. Tissue Antigens. 2001;57:447–56.CrossRefPubMed Minohara M, Ochi H, Matsushita S, Irie A, Nishimura Y, Kira J. Differences between T-cell reactivities to major myelin protein-derived peptides in opticospinal and conventional forms of multiple sclerosis and healthy controls. Tissue Antigens. 2001;57:447–56.CrossRefPubMed
31.
go back to reference Birnbaum ME, Mendoza JL, Sethi DK, Dong S, Glanville J, Dobbins J, et al. Deconstructing the peptide-MHC specificity of T cell recognition. Cell. 2014;157:1073–87.CrossRefPubMedPubMedCentral Birnbaum ME, Mendoza JL, Sethi DK, Dong S, Glanville J, Dobbins J, et al. Deconstructing the peptide-MHC specificity of T cell recognition. Cell. 2014;157:1073–87.CrossRefPubMedPubMedCentral
32.
go back to reference McElroy JP, Cree BA, Caillier SJ, Gregersen PK, Herbert J, Khan OA, et al. Refining the association of MHC with multiple sclerosis in African Americans. Hum Mol Genet. 2010;19:3080–8.CrossRefPubMedPubMedCentral McElroy JP, Cree BA, Caillier SJ, Gregersen PK, Herbert J, Khan OA, et al. Refining the association of MHC with multiple sclerosis in African Americans. Hum Mol Genet. 2010;19:3080–8.CrossRefPubMedPubMedCentral
33.
go back to reference Steinman L. Immunology of relapse and remission in multiple sclerosis. Annu Rev Immunol. 2014;32:257–81.CrossRefPubMed Steinman L. Immunology of relapse and remission in multiple sclerosis. Annu Rev Immunol. 2014;32:257–81.CrossRefPubMed
34.
go back to reference Davies S, Nicholson T, Laura M, Giovannoni G, Altmann DM. Spread of T lymphocyte immune responses to myelin epitopes with duration of multiple sclerosis. J Neuropath Exp Neurol. 2005;64:371–7.CrossRefPubMed Davies S, Nicholson T, Laura M, Giovannoni G, Altmann DM. Spread of T lymphocyte immune responses to myelin epitopes with duration of multiple sclerosis. J Neuropath Exp Neurol. 2005;64:371–7.CrossRefPubMed
35.
go back to reference Juryńczyk M, Walczak A, Jurewicz A, Jesionek-Kupnicka D, Szczepanik M, Selmaj K. Immune regulation of multiple sclerosis by transdermally applied myelin peptides. Ann Neurol. 2010;68:593–601.CrossRefPubMed Juryńczyk M, Walczak A, Jurewicz A, Jesionek-Kupnicka D, Szczepanik M, Selmaj K. Immune regulation of multiple sclerosis by transdermally applied myelin peptides. Ann Neurol. 2010;68:593–601.CrossRefPubMed
Metadata
Title
MS in South Asians in England: early disease onset and novel pattern of myelin autoimmunity
Authors
Richard S Nicholas
Vassiliki Kostadima
Maya Hanspal
Benjamin R Wakerley
Ruhena Sergeant
Saskia Decuypere
Omar Malik
Rosemary J Boyton
Daniel M Altmann
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2015
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-015-0324-2

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