Late-onset myasthenia gravis - CTLA4low genotype association and low-for-age thymic output of naïve T cells

Journal of Autoimmunity

Volumn 52, Issue , 2014, Pages 122-129

  Chuang, Wen Yu ^a,b,i   Ströbel, Philipp ^a,c,j   Bohlender Willke, Anna Lena ^c   Rieckmann, Peter ^a,k   Nix, Wilfred ^d   Schalke, Berthold ^e   Gold, Ralf ^f,l   Opitz, Andreas ^a,m   Klinker, Erdwine ^a   Inoue, Masayoshi ^a,n   Müller Hermelink, Hans Konrad ^a   Saruhan Direskeneli, Güher ^g   Bugert, Peter ^c   Willcox, Nick ^h,o   Marx, Alexander ^a,c  

^a UNIVERSITY OF WÜRZBURG   (Germany)

^b CHANG GUNG UNIVERSITY COLLEGE OF MEDICINE   (Taiwan)

^c UNIVERSITY OF HEIDELBERG   (Germany)

^d JOHANNES GUTENBERG UNIVERSITY   (Germany)

^e UNIVERSITY OF REGENSBURG   (Germany)

^f RUHR UNIVERSITY BOCHUM   (Germany)

^g ISTANBUL UNIVERSITY   (Turkey)

^h UNIVERSITY OF OXFORD   (United Kingdom)

ⁱ CHANG GUNG MEMORIAL HOSPITAL   (Taiwan)

^j UNIVERSITY OF GÖTTINGEN   (Germany)

^k KLINIKUM BAMBERG   (Germany)

^l ST JOSEF HOSPITAL   (Germany)

^m Hautklinik Kassel   (Germany)

ⁿ OSAKA UNIVERSITY   (Japan)

^o DRK Blutspendedienst Baden Württember e Hessen gGmbH   (Germany)

more..

Author keywords

AIRE; CTLA4; Myasthenia gravis; Myoid cells; Thymus; TRECs

Indexed keywords

AUTOANTIBODY; AUTOANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GENOMIC DNA; T LYMPHOCYTE RECEPTOR; CTLA4 PROTEIN, HUMAN;

ADULT; AGED; ALLELE; ARTICLE; CLINICAL FEATURE; COHORT ANALYSIS; CONTROLLED STUDY; FEMALE; GENETIC ASSOCIATION; GENOTYPE; HISTOPATHOLOGY; HUMAN; IMMUNOGENETICS; LATE ONSET MYASTHENIA GRAVIS; MAJOR CLINICAL STUDY; MALE; MONONUCLEAR CELL; MYASTHENIA GRAVIS; ONSET AGE; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; RESTRICTION FRAGMENT LENGTH POLYMORPHISM; T LYMPHOCYTE; THYMECTOMY; THYMOMA; THYMOMA ASSOCIATED MYASTHENIA GRAVIS; THYMUS; BLOOD; CAUCASIAN; HUMAN CELL; IMMUNOLOGICAL TOLERANCE; IMMUNOREGULATION; PATHOGENESIS; CELL COUNT; CELL DIFFERENTIATION; COMPLICATION; GENE FREQUENCY; GENETIC POLYMORPHISM; GENETIC PREDISPOSITION; GENETICS; IMMUNOLOGY; METABOLISM; MIDDLE AGED; NUCLEOTIDE SEQUENCE; THYMOCYTE; VERY ELDERLY;

AGED; AGED, 80 AND OVER; CELL COUNT; CELL DIFFERENTIATION; CTLA-4 ANTIGEN; DNA MUTATIONAL ANALYSIS; EUROPEAN CONTINENTAL ANCESTRY GROUP; FEMALE; GENE FREQUENCY; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HUMANS; IMMUNE TOLERANCE; MALE; MIDDLE AGED; MYASTHENIA GRAVIS; POLYMORPHISM, GENETIC; T-LYMPHOCYTES; THYMOCYTES; THYMOMA; THYMUS GLAND; THYMUS NEOPLASMS;

EID: 84904289646     PISSN: 08968411     EISSN: 10959157     Source Type: Journal    
DOI: 10.1016/j.jaut.2013.12.006     Document Type: Article

References (82)

1. Lindstrom J.M., Lennon V.A., Seybold M.E., Whittingham S. Experimental autoimmune myasthenia gravis and myasthenia gravis: biochemical and immunochemical aspects. Ann NY Acad Sci 1976, 274:254-274.
2. Toyka K.V., Brachman D.B., Pestronk A., Kao I. Myasthenia gravis: passive transfer from man to mouse. Science 1975, 190:397-399.
3. Hoch W., McConville J., Helms S., Newsom-Davis J., Melms A., Vincent A. Auto-antobodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nature Med 2001, 7:365-368.
4. Verschuuren J.J., Huijbers M.G., Plomp J.J., Niks E.H., Molenaar P.C., Martinez-Martinez P., et al. Pathophysiology of myasthenia gravis with antibodies to the acetylcholine receptor, muscle-specific kinase and low-density lipoprotein receptor-related protein 4. Autoimmun Rev 2013, 12:918-923.
5. Higuchi O., Hamuro J., Motomura M., Yamanashi Y. Autoantibodies to low-density lipoprotein receptor-related protein 4 in myasthenia gravis. Ann Neurol 2011, 69:418-422.
6. Pevzner A., Schoser B., Peters K., Cosma N.C., Karakatsani A., Schalke B., et al. Anti-LRP4 autoantibodies in AChR- and MuSK-antibody-negative myasthenia gravis. JNeurol 2012, 259:427-435.
7. Zhang B., Tzartos J.S., Belimezi M., Ragheb S., Bealmear B., Lewis R.A., et al. Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis. Arch Neurol 2012, 69:445-451.
8. Marx A., Pfister F., Schalke B., Saruhan-Direskeneli G., Melms A., Ströbel P. The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmun Rev 2013, 12:875-884.
9. Ströbel P., Moritz R., Leite M.I., Willcox N., Chuang W.Y., Gold R., et al. The ageing and myasthenic thymus: a morphometric study validating a standard procedure in the histological workup of thymic specimens. JNeuroimmunol 2008, 201-202:64-73.
10. Gregersen P.K., Kosoy R., Lee A.T., Lamb J., Sussman J., McKee D., et al. Risk for myasthenia gravis maps to a (151) Pro→Ala change in TNIP1 and to human leukocyte antigen-B*08. Ann Neurol 2012, 72:927-935.
11. Marx A., Willcox N., Leite M.I., Chuang W.Y., Schalke B., Nix W., et al. Thymoma and paraneoplastic myasthenia gravis. Autoimmunity 2010, 43:413-427.
12. Aarli J.A. Myasthenia gravis in the elderly: is it different?. Ann NY Acad Sci 2008, 1132:238-243.
13. Myking A.O., Skeie G.O., Varhaug J.E., Andersen K.S., Gilhus N.E., Aarli J.A. The histomorphology of the thymus in late onset, non-thymoma myasthenia gravis. Eur J Neurol 1998, 5:401-405.
14. high genotype is associated with myasthenia gravis in thymoma patients. Ann Neurol 2005, 58:644-648.
15. Buckley C., Douek D., Newsom-Davis J., Vincent A., Willcox N. Mature, long-lived CD4+ and CD8+ T cells are generated by the thymoma in myasthenia gravis. Ann Neurol 2001, 50:64-72.
16. Gautel M., Lakey A., Barlow D.P., Holmes Z., Scales S., Leonard K., et al. Titin antibodies in myasthenia gravis: identification of a major immunogenic region of titin. Neurology 1993, 43:1581-1585.
17. Voltz R.D., Albrich W.C., Nägele A., Schumm F., Wick M., Freiburg A., et al. Paraneoplastic myasthenia gravis: detection of anti-MGT30 (titin) antibodies predicts thymic epithelial tumor. Neurology 1997, 49:1454-1457.
18. Zivković S.A., Clemens P.R. Lacomis. Characteristics of late-onset myasthenia gravis. JNeurol 2012, 259:2167-2171.
19. Compston D.A., Vincent A., Newsom-Davis J., Batchelor J.R. Clinical, pathological, HLA antigen and immunological evidence for disease heterogeneity in myasthenia gravis. Brain 1980, 103:579-601.
20. Somnier F.E., Keiding N., Paulson O.B. Epidemiology of myasthenia gravis in Denmark. A longitudinal and comprehensive population survey. Arch Neurol 1991, 48:733-739.
21. Aarli J.A., Romi F., Skeie G.O., Gilhus N.E. Myasthenia gravis in individuals over 40. Ann NY Acad Sci 2003, 998:424-431.
22. Romi F., Aarli J.A., Gilhus N.E. Myasthenia gravis patients with ryanodine receptor antibodies have distinctive clinical features. Eur J Neurol 2007, 14:617-620.
23. Ishii W., Matsuda M., Hanyuda M., Momose M., Nakayama J., Ehara T., et al. Comparison of the histological and immunohistochemical features of the thymus in young- and elderly-onset myasthenia gravis without thymoma. JClin Neurosci 2007, 14:110-115.
24. Maniaol A.H., Elsais A., Lorentzen Å.R., Owe J.F., Viken M.K., Sæther H., et al. Late onset myasthenia gravis is associated with HLA DRB1*15:01 in the Norwegian population. PLoS One 2012, 7:e36603.
25. Evoli A., Batocchi A.P., Minisci C., Di Schino C., Tonali P. Therapeutic options in ocular myasthenia gravis. Neuromuscul Disord 2001, 11:208-216.
26. Fraisse T., Labauge P., Camu W., Arlaud P., de Wazières B. Myasthenia gravis in the elderly: diagnosis, comorbidity and course: 45 cases. Presse Med 2007, 36:9-14.
27. + T-cells in late-onset myasthenia gravis: novel parallels with thymoma patients. JNeuroimmunol 2009, 216:85-91.
28. Marx A., Pfister F., Schalke B., Nix W., Ströbel P. Thymus pathology observed in the MGTX trial. Ann NY Acad Sci 2012, 1275:92-100.
29. Carr A.S., Cardwell C.R., McCarron P.O., McConville J. Asystematic review of population based epidemiological studies in Myasthenia Gravis. BMC Neurol 2010, 10:46.
30. Matsuda M., Dohi-Iijima N., Nakamura A., Sekijima Y., Morita H., Matsuzawa S., et al. Increase in incidence of elderly-onset patients with myasthenia gravis in Nagano Prefecture, Japan. Intern Med 2005, 44:572-577.
31. Pedersen E.G., Hallas J., Hansen K., Jensen P.E., Gaist D. Late-onset myasthenia not on the increase: a nationwide register study in Denmark, 1996-2009. Eur J Neurol 2013, 20:309-314.
32. Somnier F.E. Increasing incidence of late-onset anti-AChR antibody-seropositive myasthenia gravis. Neurology 2005, 65:928-930.
33. Vincent A., Clover L., Buckley C., Evans J.G., Rothwell P.M. Evidence of underdiagnosis of myasthenia gravis in older people. JNeurol Neurosurg Psychiatry 2003, 74:1105-1108.
34. Leite M.I., Ströbel P., Jones M., Micklem K., Moritz R., Gold R., et al. Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG. Ann Neurol 2005, 57:444-448.
35. Kirchner T., Schalke B., Melms A., von Kügelgen T., Müller-Hermelink H.K. Immunohistological patterns of non-neoplastic changes in the thymus in Myasthenia gravis. Virchows Arch B Cell Pathol Incl Mol Pathol 1986, 52:237-257.
36. Van de Velde R.L., Friedman N.B. Thymic myoid cells and myasthenia gravis. Am J Pathol 1970, 59:347-368.
37. Roxanis I., Micklem K., McConville J., Newsom-Davis J., Willcox N. Thymic myoid cells and germinal center formation in myasthenia gravis; possible roles in pathogenesis. JNeuroimmunol 2002, 125:185-197.
38. Marx A., Hohenberger P., Hoffmann H., Pfannschmidt J., Schnabel P., Hofmann H.S., et al. The autoimmune regulator AIRE in thymoma biology: autoimmunity and beyond. JThorac Oncol 2010, 5:S266-S272.
39. Ströbel P., Murumägi A., Klein R., Luster M., Lahti M., Krohn K., et al. Deficiency of the autoimmune regulator AIRE in thymomas is insufficient to elicit autoimmune polyendocrinopathy syndrome type 1 (APS-1). JPathol 2007, 211:563-571.
40. Scarpino S., Di Napoli A., Stoppacciaro A., Antonelli M., Pilozzi E., Chiarle R., et al. Expression of autoimmune regulator gene (AIRE) and T regulatory cells in human thymomas. Clin Exp Immunol 2007, 149:504-512.
41. Kyewski B., Peterson P. Aire, master of many trades. Cell 2010, 140:24-26.
42. Giraud M., Taubert R., Vandiedonck C., Ke X., Lévi-Strauss M., Pagani F., et al. An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymus. Nature 2007, 448:934-937.
43. Romi F., Gilhus N.E., Varhaug J.E., Myking A., Skeie G.O., Aarli J.A. Thymectomy and anti-muscle autoantibodies in late-onset myasthenia gravis. Eur J Neurol 2002, 9:55-61.
44. Douek D.C., McFarland R.D., Keiser P.H., Gage E.A., Massey J.M., Haynes B.F., et al. Changes in thymic function with age and during the treatment of HIV infection. Nature 1998, 396:690-695.
45. Willcox N., Leite M.I., Kadota Y., Jones M., Meager A., Subrahmanyam P., et al. Autoimmunizing mechanisms in thymoma and thymus. Ann NY Acad Sci 2008, 1132:163-173.
46. Hoffacker V., Schultz A., Tiesinga J.J., Gold R., Schalke B., Nix W., et al. Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease. Blood 2000, 96:3872-3879.
47. + T cells in thymomas. Blood 2002, 100:159-166.
48. Namba T., Brunner N.G., Grob D. Myasthenia gravis in patients with thymoma, with particular reference to onset after thymectomy. Medicine (Baltimore) 1978, 57:411-433.
49. Giraud M., Beaurain G., Yamamoto A.M., Eymard B., Tranchant C., Gajdos P., et al. Linkage of HLA to myasthenia gravis and genetic heterogeneity depending on anti-titin antibodies. Neurology 2001, 57:1555-1560.
50. Hapnes L., Willcox N., Oftedal B.E., Owe J.F., Gilhus N.E., Meager A., et al. Radioligand-binding assay reveals distinct autoantibody preferences for type I interferons in APS I and myasthenia gravis subgroups. JClin Immunol 2012, 32:230-237.
51. Kisand K., Bøe Wolff A.S., Podkrajsek K.T., Tserel L., Link M., Kisand K.V., et al. Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. JExp Med 2010, 207:299-308.
52. Meager A., Wadhwa M., Dilger P., Bird C., Thorpe R., Newsom-Davis J., et al. Anti-cytokine autoantibodies in autoimmunity: preponderance of neutralizing autoantibodies against interferon-alpha, interferon-omega and interleukin-12 in patients with thymoma and/or myasthenia gravis. Clin Exp Immunol 2003, 132:128-136.
53. Meloni A., Furcas M., Cetani F., Marcocci C., Falorni A., Perniola R., et al. Autoantibodies against type I interferons as an additional diagnostic criterion for autoimmune polyendocrine syndrome type I. JClin Endocrinol Metab 2008, 93:4389-4397.
54. Alseth E.H., Nakkestad H.L., Aarseth J., Gilhus N.E., Skeie G.O. Interleukin-10 promoter polymorphisms in myasthenia gravis. JNeuroimmunol 2009, 210:63-66.
55. Vandiedonck C., Capdevielle C., Giraud M., Krumeich S., Jais J.P., Eymard B., et al. Association of the PTPN22*R620W polymorphism with autoimmune myasthenia gravis. Ann Neurol 2006, 59:404-407.
56. gain-of-function+1858T(+) genotypes correlate with low IL-2 expression in thymomas and predispose to myasthenia gravis. Genes Immun 2009, 10:667-672.
57. Vandiedonck C., Raffoux C., Eymard B., Tranchant C., Dulmet E., Krumeich S., et al. Association of HLA-A in autoimmune myasthenia gravis with thymoma. JNeuroimmunol 2009, 210:120-123.
58. Machens A., Löliger C., Pichlmeier U., Emskötter T., Busch C., Izbicki J.R. Correlation of thymic pathology with HLA in myasthenia gravis. Clin Immunol 1999, 91:296-301.
59. Janer M., Cowland A., Picard J., Campbell D., Pontarotti P., Newsom-Davis J., et al. Asusceptibility region for myasthenia gravis extending into the HLA-class I sector telomeric to HLA-C. Hum Immunol 1999, 60:909-917.
60. Saruhan-Direskeneli G., Kiliç A., Parman Y., Serdaroǧlu P., Deymeer F. HLA-DQ poly-morphism in Turkish patients with myasthenia gravis. Hum Immunol 2006, 67:352-358.
61. Testi M., Terracciano C., Guagnano A., Testa G., Marfia G.A., Pompeo E., et al. Association of HLA-DQB1*05:02 and DRB1*16 Alleles with Late-Onset, Nonthymomatous, AChR-Ab-Positive Myasthenia Gravis. Autoimmune Dis 2012, 2012:541760.
62. Baranzini S.E. The genetics of autoimmune diseases: a networked perspective. Curr Opin Immunol 2009, 21:596-605.
63. Ueda H., Howson J.M., Esposito L., Heward J., Snook H., Chamberlain G., et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 2003, 423:506-511.
64. Carreno B.M., Bennett F., Chau T.A., Ling V., Luxenberg D., Jussif J., et al. CTLA-4 (CD152) can inhibit T cell activation by two different mechanisms depending on its level of cell surface expression. JImmunol 2000, 165:1352-1356.
65. Verhagen J., Genolet R., Britton G.J., Stevenson B.J., Sabatos-Peyton C.A., Dyson J., et al. CTLA-4 controls the thymic development of both conventional and regulatory T cells through modulation of the TCR repertoire. Proc Natl Acad Sci USA 2013, 110:E221-E230.
66. Palmer E. Negative selection - clearing out the bad apples from the T-cell repertoire. Nat Rev Immunol 2003, 3:383-391.
67. Anjos S., Nguyen A., Ounissi-Benkalha H., Tessier M.C., Polychronakos C. Acommon autoimmunity predisposing signal peptide variant of the cytotoxic T-lymphocyte antigen 4 results in inefficient glycosylation of the susceptibility allele. JBiol Chem 2002, 277:46478-46486.
68. Sarzotti M., Patel D.D., Li X., Ozaki D.A., Cao S., Langdon S., et al. Tcell repertoire development in humans with SCID after nonablative allogeneic marrow transplantation. JImmunol 2003, 170:2711-2718.
69. Tackenberg B., Kruth J., Bartholomaeus J.E., Schlegel K., Oertel W.H., Willcox N., et al. Clonal expansions of CD4+ B helper T cells in autoimmune myasthenia gravis. Eur J Immunol 2007, 37:849-863.
70. Hug A., Korporal M., Schröder I., Haas J., Glatz K., Storch-Hagenlocher B., et al. Thymic export function and T cell homeostasis in patients with relapsing remitting multiple sclerosis. JImmunol 2003, 171:432-437.
71. Kayser C., Alberto F.L., da Silva N.P., Andrade L.E. Decreased number of T cells bearing TCR rearrangement excision circles (TREC) in active recent onset systemic lupus erythematosus. Lupus 2004, 13:906-911.
72. Koetz K., Bryl E., Spickschen K., O'Fallon W.M., Goronzy J.J., Weyand C.M. Tcell homeostasis in patients with rheumatoid arthritis. Proc Natl Acad Sci USA 2000, 97:9203-9208.
73. Bagos P.G., Karnaouri A.C., Nikolopoulos G.K., Hamodrakas S.J. No evidence for association of CTLA-4 gene polymorphisms with the risk of developing multiple sclerosis: a meta-analysis. Mult Scler 2007, 13:156-168.
74. Chang W.W., Zhang L., Yao Y.S., Su H. Association between CTLA-4 exon-1+49A/G polymorphism and systemic lupus erythematosus: an updated analysis. Mol Biol Rep 2012, 39:9159-9165.
75. Li X., Zhang C., Zhang J., Zhang Y., Wu Z., Yang L., et al. Polymorphisms in the CTLA-4 gene and rheumatoid arthritis susceptibility: a meta-analysis. JClin Immunol 2012, 32:530-539.
76. Tang M.J., Zhou Z.B. Association of the CTLA-4+49A/G polymorphism with rheumatoid arthritis in Chinese Han population. Mol Biol Rep 2013, 40:2627-2631.
77. Lee Y.H., Harley J.B., Nath S.K. CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis. Hum Genet 2005, 116:361-367.
78. Sempowski G.D., Thomasch J.R., Gooding M.E., Hale L.P., Edwards L.J., Ciafaloni E., et al. Effect of of thymectomy on human peripheral blood T cell pools in myasthenia gravis. JImmunol 2001, 166:2808-2817.
79. Hazenberg M.D., Verschuren M.C., Hamann D., Miedema F., van Dongen J.J. Tcell receptor excision circles as markers for recent thymic emigrants: basic aspects, technical approach, and guidelines for interpretation. JMol Med (Berl) 2001, 79:631-640. Curr Opin Allergy Clin Immunol 2011;11:517-24.
80. Somech R. T-cell receptor excision circles in primary immunodeficiencies and other T-cell immune disorders.
81. Bains I., Thiébaut R., Yates A.J., Callard R. Quantifying thymic export: combining models of naive T cell proliferation and TCR excision circle dynamics gives an explicit measure of thymic output. JImmunol 2009, 183:4329-4336.
82. Bernasconi P., Barberis M., Baggi F., Passerini L., Cannone M., Arnoldi E., et al. Increased toll-like receptor 4 expression in thymus of myasthenic patients with thymitis and thymic involution. Am J Pathol 2005, 167:129-139.