Biomarkers in multiple sclero'sis

Clinical Immunology

Volumn 161, Issue 1, 2015, Pages 51-58

  Housley, William J ^a   Pitt, David ^a   Hafler, David A ^a,b  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

Biomarkers; Multiple sclerosis

Indexed keywords

ANTIBODY; BIOLOGICAL MARKER; CD163 ANTIGEN; CXCL13 CHEMOKINE; GLIAL FIBRILLARY ACIDIC PROTEIN; IMMUNOGLOBULIN G; KIR4.1 ANTIBODY; LIPOPEPTIDE; MESSENGER RNA; MICRORNA; NATALIZUMAB; OLIGOCLONAL BAND; OSTEOPONTIN; PROTEIN; UNCLASSIFIED DRUG; VIRUS ANTIBODY; YKL 40 PROTEIN;

ANTIBODY TITER; ARTICLE; CEREBROSPINAL FLUID; DISEASE COURSE; GENE MAPPING; GENETIC PREDISPOSITION; GENETICS; MICROBIOME; MULTIPLE SCLEROSIS; NERVE DEGENERATION; NEUROFILAMENT; NUCLEAR MAGNETIC RESONANCE IMAGING; PRIORITY JOURNAL; T LYMPHOCYTE; TREATMENT RESPONSE; BRAIN; HUMAN; IMMUNOLOGY; JC VIRUS; PATHOLOGY; RADIOGRAPHY; SENSITIVITY AND SPECIFICITY;

ANTIBODIES, VIRAL; BIOMARKERS; BRAIN; HUMANS; IMMUNOGLOBULIN G; JC VIRUS; MAGNETIC RESONANCE IMAGING; MICRORNAS; MULTIPLE SCLEROSIS; SENSITIVITY AND SPECIFICITY;

EID: 84949315380     PISSN: 15216616     EISSN: 15217035     Source Type: Journal    
DOI: 10.1016/j.clim.2015.06.015     Document Type: Article

References (145)

1. Nylander A., Hafler D.A. Multiple sclerosis. J. Clin. Invest. Apr, 2012, 122:1180.
2. Sawcer S., et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature Aug 11, 2011, 476:214.
3. Patsopoulos N.A., et al. Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci. Ann. Neurol. Dec, 2011, 70:897.
4. C.International Multiple Sclerosis Genetics, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat. Genet. Nov, 2013, 45:1353.
5. Ascherio A. Environmental factors in multiple sclerosis. Expert. Rev. Neurother. Dec, 2013, 13:3.
6. McDonald W.I., et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann. Neurol. Jul, 2001, 50:121.
7. Polman C.H., et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann. Neurol. Feb, 2011, 69:292.
8. Polman C.H., et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann. Neurol. Dec, 2005, 58:840.
9. Miller D., Barkhof F., Montalban X., Thompson A., Filippi M. Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis. Lancet Neurol. May, 2005, 4:281.
10. Gunnarsson M., et al. Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab. Ann. Neurol. Jan, 2011, 69:83.
11. Jones J.L., et al. Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity. Brain Aug, 2010, 133:2232.
12. Lowenthal A., Vansande M., Karcher D. The differential diagnosis of neurological diseases by fractionating electrophoretically the CSF gamma-globulins. J. Neurochem. Aug, 1960, 6:51.
13. Yahr M.D., Kabat E.A. Cerebrospinal fluid and serum gamma globulin levels in multiple sclerosis: changes induced by large doses of prednisone. Transactions of the American Neurological Association 82nd Meeting 1957, 115.
14. Davenport R.D., Keren D.F. Oligoclonal bands in cerebrospinal fluids: significance of corresponding bands in serum for diagnosis of multiple sclerosis. Clin. Chem. Apr, 1988, 34:764.
15. Poser C.M., et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann. Neurol. Mar, 1983, 13:227.
16. Ignacio R. Oligoclonal bands and MRI in clinically isolated syndromes: predicting conversion time to multiple sclerosis. J. Neurol. Jul, 2010, 257:1188.
17. Kuhle J., et al. Conversion from clinically isolated syndrome to multiple sclerosis: a large multicentre study. Mult. Scler. Feb 13 2015.
18. Stangel M., et al. The utility of cerebrospinal fluid analysis in patients with multiple sclerosis. Nat. Rev. Neurol. May, 2013, 9:267.
19. Barkhof F. MRI in multiple sclerosis: correlation with expanded disability status scale (EDSS). Mult. Scler. Aug, 1999, 5:283.
20. Fisniku L.K., et al. Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain Mar, 2008, 131:808.
21. Zivadinov R., Leist T.P. Clinical-magnetic resonance imaging correlations in multiple sclerosis. J. Neuroimaging 2005, 15:10S.
22. Li D.K., et al. MRI T2 lesion burden in multiple sclerosis: a plateauing relationship with clinical disability. Neurology May 9, 2006, 66:1384.
23. Prosperini L., Gallo V., Petsas N., Borriello G., Pozzilli C. One-year MRI scan predicts clinical response to interferon beta in multiple sclerosis. Eur. J. Neurol. Nov, 2009, 16:1202.
24. Rio J., et al. Measures in the first year of therapy predict the response to interferon beta in MS. Mult. Scler. Jul, 2009, 15:848.
25. Bruck W., et al. Inflammatory central nervous system demyelination: correlation of magnetic resonance imaging findings with lesion pathology. Ann. Neurol. Nov, 1997, 42:783.
26. Katz D., et al. Correlation between magnetic resonance imaging findings and lesion development in chronic, active multiple sclerosis. Ann. Neurol. Nov, 1993, 34:661.
27. Khoury S.J., et al. Longitudinal MRI in multiple sclerosis: correlation between disability and lesion burden. Neurology Nov, 1994, 44:2120.
28. Smith M.E., et al. Clinical worsening in multiple sclerosis is associated with increased frequency and area of gadopentetate dimeglumine-enhancing magnetic resonance imaging lesions. Ann. Neurol. May, 1993, 33:480.
29. Rocca M.A., et al. Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis. Lancet Neurol. Mar, 2015, 14:302.
30. Geurts J.J., Calabrese M., Fisher E., Rudick R.A. Measurement and clinical effect of grey matter pathology in multiple sclerosis. Lancet Neurol. Dec, 2012, 11:1082.
31. Barkhof F., Calabresi P.A., Miller D.H., Reingold S.C. Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat. Rev. Neurol. May, 2009, 5:256.
32. Polman C.H., et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med. Mar 2, 2006, 354:899.
33. Antoniol C., Stankoff B. Immunological markers for PML prediction in MS patients treated with natalizumab. Front. Immunol. 2014, 5:668.
34. Brew B.J., Davies N.W., Cinque P., Clifford D.B., Nath A. Progressive multifocal leukoencephalopathy and other forms of JC virus disease. Nat. Rev. Neurol. Dec, 2010, 6:667.
35. Outteryck O., et al. JC-virus seroconversion in multiple sclerosis patients receiving natalizumab. Mult. Scler. 2014, 20(7):822-829.
36. Olsson T., et al. Anti-JC virus antibody prevalence in a multinational multiple sclerosis cohort. Mult. Scler. Oct, 2013, 19:1533.
37. Plavina T., et al. Anti-JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal leukoencephalopathy. Ann. Neurol. Dec, 2014, 76:802.
38. Kuhle J., et al. Neurofilament light and heavy subunits compared as therapeutic biomarkers in multiple sclerosis. Acta Neurol. Scand. Dec, 2013, 128:e33.
39. Bielekova B., McDermott M.P. Will CSF biomarkers guide future therapeutic decisions in multiple sclerosis?. Neurology Apr 21, 2015, 84:1620.
40. Disanto G., et al. Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome. J. Neurol. Neurosurg. Psychiatry Feb 25, 2015, http://dx.doi.org/10.1136/jnnp-2014-309690.
41. Salzer J., Svenningsson A., Sundstrom P. Neurofilament light as a prognostic marker in multiple sclerosis. Mult. Scler. Mar, 2010, 16:287.
42. Modvig S., et al. Cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain predict multiple sclerosis development and disability after optic neuritis. Mult. Scler. Feb 19, 2015.
43. Martinez M.A., et al. Glial and neuronal markers in cerebrospinal fluid predict progression in multiple sclerosis. Mult. Scler. Apr, 2015, 21:550.
44. Kuhle J., et al. Fingolimod and CSF neurofilament light chain levels in relapsing-remitting multiple sclerosis. Neurology Apr 21, 2015, 84:1639.
45. Romme Christensen J., et al. Natalizumab in progressive MS: results of an open-label, phase 2A, proof-of-concept trial. Neurology Apr 29, 2014, 82:1499.
46. Malmestrom C., Haghighi S., Rosengren L., Andersen O., Lycke J. Neurofilament light protein and glial fibrillary acidic protein as biological markers in MS. Neurology Dec 23, 2003, 61:1720.
47. Norgren N., et al. Neurofilament and glial fibrillary acidic protein in multiple sclerosis. Neurology Nov 9, 2004, 63:1586.
48. Rosengren L.E., Lycke J., Andersen O. Glial fibrillary acidic protein in CSF of multiple sclerosis patients: relation to neurological deficit. J. Neurol. Sci. Nov, 1995, 133:61.
49. Petzold A., et al. Markers for different glial cell responses in multiple sclerosis: clinical and pathological correlations. Brain Jul, 2002, 125:1462.
50. Cohen S.R., Herndon R.M., McKhann G.M. Radioimmunoassay of myelin basic protein in spinal fluid. An index of active demyelination. N. Engl. J. Med. Dec 23, 1976, 295:1455.
51. Whitaker J.N. Myelin encephalitogenic protein fragments in cerebrospinal fluid of persons with multiple sclerosis. Neurology Oct, 1977, 27:911.
52. Avsar T., et al. Protein biomarkers for multiple sclerosis: semi-quantitative analysis of cerebrospinal fluid candidate protein biomarkers in different forms of multiple sclerosis. Mult. Scler. Aug, 2012, 18:1081.
53. Massaro A.R., Tonali P. Cerebrospinal fluid markers in multiple sclerosis: an overview. Mult. Scler. Feb, 1998, 4:1.
54. Burman J., et al. Assessing tissue damage in multiple sclerosis: a biomarker approach. Acta Neurol. Scand. Aug, 2014, 130:81.
55. Verbeek M.M., De Jong D., Kremer H.P. Brain-specific proteins in cerebrospinal fluid for the diagnosis of neurodegenerative diseases. Ann. Clin. Biochem. Jan, 2003, 40:25.
56. Davis B.H., Zarev P.V. Human monocyte CD163 expression inversely correlates with soluble CD163 plasma levels. Cytometry B Clin. Cytom. Jan, 2005, 63:16.
57. Stilund M., et al. Soluble CD163 as a marker of macrophage activity in newly diagnosed patients with multiple sclerosis. PLoS ONE 2014, 9:e98588.
58. Fabriek B.O., et al. Proteolytic shedding of the macrophage scavenger receptor CD163 in multiple sclerosis. J. Neuroimmunol. Jul, 2007, 187:179.
59. Stilund M., et al. Biomarkers of inflammation and axonal degeneration/damage in patients with newly diagnosed multiple sclerosis: contributions of the soluble CD163 CSF/serum ratio to a biomarker panel. PLoS ONE 2015, 10:e0119681.
60. Canto E., et al. Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes. Brain Apr, 2015, 138:918.
61. Peltomaa R., Paimela L., Harvey S., Helve T., Leirisalo-Repo M. Increased level of YKL-40 in sera from patients with early rheumatoid arthritis: a new marker for disease activity. Rheumatol. Int. Jul, 2001, 20:192.
62. Vos K., et al. Raised human cartilage glycoprotein-39 plasma levels in patients with rheumatoid arthritis and other inflammatory conditions. Ann. Rheum. Dis. Jul, 2000, 59:544.
63. Vind I., Johansen J.S., Price P.A., Munkholm P. Serum YKL-40, a potential new marker of disease activity in patients with inflammatory bowel disease. Scand. J. Gastroenterol. Jun, 2003, 38:599.
64. Comabella M., et al. Cerebrospinal fluid chitinase 3-like 1 levels are associated with conversion to multiple sclerosis. Brain Apr, 2010, 133:1082.
65. Legler D.F., et al. B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5. J. Exp. Med. Feb 16, 1998, 187:655.
66. Festa E.D., et al. Serum levels of CXCL13 are elevated in active multiple sclerosis. Mult. Scler. Nov, 2009, 15:1271.
67. Khademi M., et al. Cerebrospinal fluid CXCL13 in multiple sclerosis: a suggestive prognostic marker for the disease course. Mult. Scler. Mar, 2011, 17:335.
68. Brettschneider J., et al. The chemokine CXCL13 is a prognostic marker in clinically isolated syndrome (CIS). PLoS ONE 2010, 5:e11986.
69. Felgenhauer K., Reiber H. The diagnostic significance of antibody specificity indices in multiple sclerosis and herpes virus induced diseases of the nervous system. Clin. Investig. Jan, 1992, 70:28.
70. Salmi A.A. Virus antibodies in patients with multiple sclerosis. Ann. Clin. Res. Oct, 1973, 5:319.
71. Rosche B., et al. Measles IgG antibody index correlates with T2 lesion load on MRI in patients with early multiple sclerosis. PLoS ONE 2012, 7:e28094.
72. Brettschneider J., et al. IgG antibodies against measles, rubella, and varicella zoster virus predict conversion to multiple sclerosis in clinically isolated syndrome. PLoS ONE 2009, 4:e7638.
73. Jarius S., et al. The intrathecal, polyspecific antiviral immune response: specific for MS or a general marker of CNS autoimmunity?. J. Neurol. Sci. May 15, 2009, 280:98.
74. De Jager P.L., et al. Integrating risk factors: HLA-DRB1*1501 and Epstein-Barr virus in multiple sclerosis. Neurology Mar 25, 2008, 70:1113.
75. Skorstad G., Vandvik B., Vartdal F., Holmoy T. MS and clinically isolated syndromes: shared specificity but diverging clonal patterns of virus-specific IgG antibodies produced in vivo and by CSF B cells in vitro. Eur. J. Neurol. Oct, 2009, 16:1124.
76. Fenoglio C., et al. Expression and genetic analysis of miRNAs involved in CD4+ cell activation in patients with multiple sclerosis. Neurosci. Lett. Oct 17, 2011, 504:9.
77. Junker A., et al. MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain Dec, 2009, 132:3342.
78. Keller A., et al. Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls. PLoS ONE 2009, 4:e7440.
79. Lindberg R.L., Hoffmann F., Mehling M., Kuhle J., Kappos L. Altered expression of miR-17-5p in CD4+ lymphocytes of relapsing-remitting multiple sclerosis patients. Eur. J. Immunol. Mar, 2010, 40:888.
80. Otaegui D., et al. Differential micro RNA expression in PBMC from multiple sclerosis patients. PLoS ONE 2009, 4:e6309.
81. Ridolfi E., et al. Expression and genetic analysis of microRNAs involved in multiple sclerosis. Int. J. Mol. Sci. 2013, 14:4375.
82. Siegel S.R., Mackenzie J., Chaplin G., Jablonski N.G., Griffiths L. Circulating microRNAs involved in multiple sclerosis. Mol. Biol. Rep. May, 2012, 39:6219.
83. Cox M.B., et al. MicroRNAs miR-17 and miR-20a inhibit T cell activation genes and are under-expressed in MS whole blood. PLoS ONE 2010, 5:e12132.
84. Guerau-de-Arellano M., et al. Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity. Brain Dec, 2011, 134:3578.
85. Haghikia A., et al. Regulated microRNAs in the CSF of patients with multiple sclerosis: a case-control study. Neurology Nov 27, 2012, 79:2166.
86. Sievers C., et al. Altered microRNA expression in B lymphocytes in multiple sclerosis: towards a better understanding of treatment effects. Clin. Immunol. Jul, 2012, 144:70.
87. Thamilarasan M., Koczan D., Hecker M., Paap B., Zettl U.K. MicroRNAs in multiple sclerosis and experimental autoimmune encephalomyelitis. Autoimmun. Rev. Jan, 2012, 11:174.
88. Achiron A., Feldman A., Gurevich M. Molecular profiling of glatiramer acetate early treatment effects in multiple sclerosis. Dis. Markers 2009, 27:63.
89. Goertsches R.H., et al. Long-term genome-wide blood RNA expression profiles yield novel molecular response candidates for IFN-beta-1b treatment in relapsing remitting MS. Pharmacogenomics Feb, 2010, 11:147.
90. Hecker M., et al. Network analysis of transcriptional regulation in response to intramuscular interferon-beta-1a multiple sclerosis treatment. Pharmacogenomics J. Aug, 2012, 12:360.
91. Hecker M., et al. Reassessment of blood gene expression markers for the prognosis of relapsing-remitting multiple sclerosis. PLoS ONE 2011, 6:e29648.
92. Hong J., Zang Y.C., Hutton G., Rivera V.M., Zhang J.Z. Gene expression profiling of relevant biomarkers for treatment evaluation in multiple sclerosis. J. Neuroimmunol. Jul, 2004, 152:126.
93. Satoh J., et al. Microarray analysis identifies an aberrant expression of apoptosis and DNA damage-regulatory genes in multiple sclerosis. Neurobiol. Dis. Apr, 2005, 18:537.
94. Serrano-Fernandez P., et al. Time course transcriptomics of IFNB1b drug therapy in multiple sclerosis. Autoimmunity Mar, 2010, 43:172.
95. Singh M.K., et al. Gene expression changes in peripheral blood mononuclear cells from multiple sclerosis patients undergoing beta-interferon therapy. J. Neurol. Sci. Jul 15, 2007, 258:52.
96. Sturzebecher S., et al. Expression profiling identifies responder and non-responder phenotypes to interferon-beta in multiple sclerosis. Brain Jun, 2003, 126:1419.
97. Weinstock-Guttman B., et al. Genomic effects of IFN-beta in multiple sclerosis patients. J. Immunol. Sep 1, 2003, 171:2694.
98. Raphael I., Webb J., Stuve O., Haskins W., Forsthuber T. Body fluid biomarkers in multiple sclerosis: how far we have come and how they could affect the clinic now and in the future. Expert. Rev. Clin. Immunol. Jan, 2015, 11:69.
99. Cao Y., et al. Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis. Sci. Transl. Med. 2014, 7(287):287ra74.
100. Martin R., et al. A myelin basic protein peptide is recognized by cytotoxic T cells in the context of four HLA-DR types associated with multiple sclerosis. J. Exp. Med. Jan 1, 1991, 173:19.
101. Ota K., et al. T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature Jul 12, 1990, 346:183.
102. Pette M., et al. Myelin basic protein-specific T lymphocyte lines from MS patients and healthy individuals. Neurology Nov, 1990, 40:1770.
103. Raddassi K., et al. Increased frequencies of myelin oligodendrocyte glycoprotein/MHC class II-binding CD4 cells in patients with multiple sclerosis. J. Immunol. Jul 15, 2011, 187:1039.
104. Lennon V.A., Kryzer T.J., Pittock S.J., Verkman A.S., Hinson S.R. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J. Exp. Med. Aug 15, 2005, 202:473.
105. Owens G.P., Burgoon M.P., Devlin M.E., Gilden D.H. Extraction and purification of active IgG from SSPE and MS brain. J. Virol. Methods Nov, 1997, 68:119.
106. Meinl E., Derfuss T., Krumbholz M., Probstel A.K., Hohlfeld R. Humoral autoimmunity in multiple sclerosis. J. Neurol. Sci. Jul 15, 2011, 306:180.
107. Olsen M.L., Sontheimer H. Functional implications for Kir4.1 channels in glial biology: from K+ buffering to cell differentiation. J. Neurochem. Nov, 2008, 107:589.
108. Srivastava R., et al. Potassium channel KIR4.1 as an immune target in multiple sclerosis. N. Engl. J. Med. Jul 12, 2012, 115.
109. Chabas D., et al. The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science Nov 23, 2001, 294:1731.
110. Sinclair C., Mirakhur M., Kirk J., Farrell M., McQuaid S. Up-regulation of osteopontin and alphaBeta-crystallin in the normal-appearing white matter of multiple sclerosis: an immunohistochemical study utilizing tissue microarrays. Neuropathol. Appl. Neurobiol. Jun, 2005, 31:292.
111. Comabella M., et al. Plasma osteopontin levels in multiple sclerosis. J. Neuroimmunol. Jan, 2005, 158:231.
112. Szalardy L., et al. Evaluating biomarkers of neuronal degeneration and neuroinflammation in CSF of patients with multiple sclerosis-osteopontin as a potential marker of clinical severity. J. Neurol. Sci. Aug 15, 2013, 331:38.
113. Vogt M.H., et al. Osteopontin levels and increased disease activity in relapsing-remitting multiple sclerosis patients. J. Neuroimmunol. Oct, 2004, 155:155.
114. Vogt M.H., Lopatinskaya L., Smits M., Polman C.H., Nagelkerken L. Elevated osteopontin levels in active relapsing-remitting multiple sclerosis. Ann. Neurol. Jun, 2003, 53:819.
115. Wen S.R., et al. Increased levels of IL-23 and osteopontin in serum and cerebrospinal fluid of multiple sclerosis patients. J. Neuroimmunol. Mar, 2012, 244:94.
116. Bornsen L., Khademi M., Olsson T., Sorensen P.S., Sellebjerg F. Osteopontin concentrations are increased in cerebrospinal fluid during attacks of multiple sclerosis. Mult. Scler. Jan, 2011, 17:32.
117. Kivisakk P., et al. Evaluation of circulating osteopontin levels in an unselected cohort of patients with multiple sclerosis: relevance for biomarker development. Mult. Scler. Apr, 2014, 20:438.
118. Runia T.F., van Meurs M., Nasserinejad K., Hintzen R.Q. No evidence for an association of osteopontin plasma levels with disease activity in multiple sclerosis. Mult. Scler. Oct, 2014, 20:1670.
119. Lee Y.K., Menezes J.S., Umesaki Y., Mazmanian S.K. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. U. S. A. Mar 15, 2011, 108(Suppl. 1):4615.
120. Ochoa-Reparaz J., et al. Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis. J. Immunol. Nov 15, 2009, 183:6041.
121. Wu H.J., et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity Jun 25, 2010, 32:815.
122. Clark R.B., et al. Serine lipids of Porphyromonas gingivalis are human and mouse Toll-like receptor 2 ligands. Infect. Immun. Sep, 2013, 81:3479.
123. Farrokhi V., et al. Bacterial lipodipeptide, lipid 654, is a microbiome-associated biomarker for multiple sclerosis. Clin. Transl. Immunol. Nov, 2013, 2:e8.
124. Altshuler D., Daly M.J., Lander E.S. Genetic mapping in human disease. Science Nov 7, 2008, 322:881.
125. Anderson M.S., et al. Projection of an immunological self shadow within the thymus by the aire protein. Science Nov 15, 2002, 298:1395.
126. Hindorff L.A., et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl. Acad. Sci. U. S. A. Jun 9, 2009, 106:9362.
127. Welter D., et al. The NHGRI GWAS catalog, a curated resource of SNP-trait associations. Nucleic Acids Res. Jan, 2014, 42:D1001.
128. C.International Multiple Sclerosis Genetics, et al. Risk alleles for multiple sclerosis identified by a genomewide study. N. Engl. J. Med. Aug 30, 2007, 357:851.
129. Cozen W., et al. A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32. Blood Jan 12, 2012, 119:469.
130. Hunt K.A., et al. Rare and functional SIAE variants are not associated with autoimmune disease risk in up to 66,924 individuals of European ancestry. Nat. Genet. Jan, 2012, 44:3.
131. Farh K.K., et al. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature 2014, 518:337-343.
132. Genomes Project C., et al. An integrated map of genetic variation from 1,092 human genomes. Nature Nov 1, 2012, 491:56.
133. Cotsapas C., et al. Pervasive sharing of genetic effects in autoimmune disease. PLoS Genet. Aug, 2011, 7:e1002254.
134. Schneider A., et al. In active relapsing-remitting multiple sclerosis, effector T cell resistance to adaptive T(regs) involves IL-6-mediated signaling. Sci. Transl. Med. Jan 30, 2013, 5:170ra15.
135. Housley W.J., et al. Genetic variants associated with autoimmunity drive NFκB signaling and responses to inflammatory stimuli. Sci. Transl. Med. 2015, 7(291):291ra93.
136. Goris A., et al. Genetic variants are major determinants of CSF antibody levels in multiple sclerosis. Brain Mar, 2015, 138:632.
137. Buck D., et al. Genetic variants in the immunoglobulin heavy chain locus are associated with the IgG index in multiple sclerosis. Ann. Neurol. Jan, 2013, 73:86.
138. Idiman E., Ozakbas S., Dogan Y., Kosehasanogullari G. The significance of oligoclonal bands in multiple sclerosis: relevance of demographic and clinical features, and immunogenetic backgrounds. J. Neuroimmunol. Jul 25, 2009, 212:121.
139. Imrell K., Landtblom A.M., Hillert J., Masterman T. Multiple sclerosis with and without CSF bands: clinically indistinguishable but immunogenetically distinct. Neurology Sep 26, 2006, 67:1062.
140. Kikuchi S., et al. HLA-related subpopulations of MS in Japanese with and without oligoclonal IgG bands. Human leukocyte antigen. Neurology Feb 25, 2003, 60:647.
141. Leone M.A., et al. Association of genetic markers with CSF oligoclonal bands in multiple sclerosis patients. PLoS ONE 2013, 8:e64408.
142. Mero I.L., et al. Oligoclonal band status in Scandinavian multiple sclerosis patients is associated with specific genetic risk alleles. PLoS ONE 2013, 8:e58352.
143. Romero-Pinel L., et al. Association of HLA-DRB1*15 allele and CSF oligoclonal bands in a Spanish multiple sclerosis cohort. Eur. J. Neurol. Oct, 2011, 18:1258.
144. Wu J.S., et al. Presence of CSF oligoclonal bands (OCB) is associated with the HLA-DRB1 genotype in a West Australian multiple sclerosis cohort. J. Neurol. Sci. Jan 15, 2010, 288:63.
145. Yoshimura S., et al. Genetic and infectious profiles influence cerebrospinal fluid IgG abnormality in Japanese multiple sclerosis patients. PLoS ONE 2014, 9:e95367.