Prediction and Pathogenesis in Type 1 Diabetes

Immunity

Volumn 32, Issue 4, 2010, Pages 468-478

  Ziegler, Anette G ^a   Nepom, Gerald T ^b  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^b BENAROYA RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIBODY; AUTOANTIGEN; HLA ANTIGEN; INTERFERON ANTIBODY; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; MONOCLONAL ANTIBODY CD3; NON RECEPTOR PROTEIN TYROSINE PHOSPHATASE 22; RAPAMYCIN; BIOLOGICAL MARKER;

ANTIGEN ANTIBODY REACTION; AUTOIMMUNE DISEASE; CD4+ T LYMPHOCYTE; CLINICAL TRIAL; DIABETOGENESIS; DISEASE COURSE; DISEASE MARKER; DISEASE PREDISPOSITION; GENETIC ASSOCIATION; GENETIC RISK; GENETIC VARIABILITY; GENOTYPE; HOMEOSTASIS; HUMAN; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; IMMUNOPATHOGENESIS; IMMUNOREGULATION; IMMUNOSTIMULATION; INSULIN DEPENDENT DIABETES MELLITUS; JUVENILE RHEUMATOID ARTHRITIS; NONHUMAN; PREDICTION; PRIORITY JOURNAL; REVIEW; SYSTEMIC LUPUS ERYTHEMATOSUS; ANIMAL; GENETIC PREDISPOSITION; GENETICS; IMMUNOLOGY; RISK FACTOR;

ANIMALS; BIOLOGICAL MARKERS; DIABETES MELLITUS, TYPE 1; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; HUMANS; RISK FACTORS;

EID: 77951891703     PISSN: 10747613     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.immuni.2010.03.018     Document Type: Review

References (98)

1. Achenbach P., Koczwara K., Knopff A., Naserke H., Ziegler A.G., Bonifacio E. Mature high-affinity immune responses to (pro)insulin anticipate the autoimmune cascade that leads to type 1 diabetes. J. Clin. Invest. 2004, 114:589-597.
2. Achenbach P., Warncke K., Reiter J., Naserke H.E., Williams A.J., Bingley P.J., Bonifacio E., Ziegler A.G. Stratification of type 1 diabetes risk on the basis of islet autoantibody characteristics. Diabetes 2004, 53:384-392.
3. Achenbach P., Warncke K., Reiter J., Williams A.J., Ziegler A.G., Bingley P.J., Bonifacio E. Type 1 diabetes risk assessment: Improvement by follow-up measurements in young islet autoantibody-positive relatives. Diabetologia 2006, 49:2969-2976.
4. Achenbach P., Schlosser M., Williams A.J., Yu L., Mueller P.W., Bingley P.J., Bonifacio E. Combined testing of antibody titer and affinity improves insulin autoantibody measurement: Diabetes Antibody Standardization Program. Clin. Immunol. 2007, 122:85-90.
5. Achenbach P., Lampasona V., Landherr U., Koczwara K., Krause S., Grallert H., Winkler C., Pflüger M., Illig T., Bonifacio E., Ziegler A.G. Autoantibodies to zinc transporter 8 and SLC30A8 genotype stratify type 1 diabetes risk. Diabetologia 2009, 52:1881-1888.
6. Allantaz F., Chaussabel D., Stichweh D., Bennett L., Allman W., Mejias A., Ardura M., Chung W., Smith E., Wise C., et al. Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade. J. Exp. Med. 2007, 204:2131-2144.
7. Aly T.A., Ide A., Jahromi M.M., Barker J.M., Fernando M.S., Babu S.R., Yu L., Miao D., Erlich H.A., Fain P.R., et al. Extreme genetic risk for type 1A diabetes. Proc. Natl. Acad. Sci. USA 2006, 103:14074-14079.
8. Arechiga A.F., Habib T., He Y., Zhang X., Zhang Z.Y., Funk A., Buckner J.H. Cutting edge: The PTPN22 allelic variant associated with autoimmunity impairs B cell signaling. J. Immunol. 2009, 182:3343-3347.
9. Baekkeskov S., Aanstoot H.J., Christgau S., Reetz A., Solimena M., Cascalho M., Folli F., Richter-Olesen H., De Camilli P., Camilli P.D. Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 1990, 347:151-156.
10. Baisch J.M., Weeks T., Giles R., Hoover M., Stastny P., Capra J.D. Analysis of HLA-DQ genotypes and susceptibility in insulin-dependent diabetes mellitus. N. Engl. J. Med. 1990, 322:1836-1841.
11. Battaglia M., Stabilini A., Migliavacca B., Horejs-Hoeck J., Kaupper T., Roncarolo M.G. Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J. Immunol. 2006, 177:8338-8347.
12. Beeton C., Wulff H., Standifer N.E., Azam P., Mullen K.M., Pennington M.W., Kolski-Andreaco A., Wei E., Grino A., Counts D.R., et al. Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Proc. Natl. Acad. Sci. USA 2006, 103:17414-17419.
13. Begovich A.B., Carlton V.E., Honigberg L.A., Schrodi S.J., Chokkalingam A.P., Alexander H.C., Ardlie K.G., Huang Q., Smith A.M., Spoerke J.M., et al. A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am. J. Hum. Genet. 2004, 75:330-337.
14. Bennett S.T., Lucassen A.M., Gough S.C., Powell E.E., Undlien D.E., Pritchard L.E., Merriman M.E., Kawaguchi Y., Dronsfield M.J., Pociot F., et al. Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus. Nat. Genet. 1995, 9:284-292.
15. Bergholdt R., Brorsson C., Lage K., Nielsen J.H., Brunak S., Pociot F. Expression profiling of human genetic and protein interaction networks in type 1 diabetes. PLoS ONE 2009, 4:e6250.
16. Bielekova B., Sung M.H., Kadom N., Simon R., McFarland H., Martin R. Expansion and functional relevance of high-avidity myelin-specific CD4+ T cells in multiple sclerosis. J. Immunol. 2004, 172:3893-3904.
17. Bingley P.J. Interactions of age, islet cell antibodies, insulin autoantibodies, and first-phase insulin response in predicting risk of progression to IDDM in ICA+ relatives: The ICARUS data set. Islet Cell Antibody Register Users Study. Diabetes 1996, 45:1720-1728.
18. Bingley P.J., Christie M.R., Bonifacio E., Bonfanti R., Shattock M., Fonte M.T., Bottazzo G.F., Gale E.A. Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives. Diabetes 1994, 43:1304-1310.
19. Bingley P.J., Bonifacio E., Ziegler A.G., Schatz D.A., Atkinson M.A., Eisenbarth G.S. Proposed guidelines on screening for risk of type 1 diabetes. Diabetes Care 2001, 24:398. Immunology of Diabetes Society.
20. Bingley P.J., Bonifacio E., Mueller P.W. Diabetes antibody standardization program: First assay proficiency evaluation. Diabetes 2003, 52:1128-1136.
21. Bisikirska B., Colgan J., Luban J., Bluestone J.A., Herold K.C. TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs. J. Clin. Invest. 2005, 115:2904-2913.
22. Bonifacio E., Scirpoli M., Kredel K., Füchtenbusch M., Ziegler A.G. Early autoantibody responses in prediabetes are IgG1 dominated and suggest antigen-specific regulation. J. Immunol. 1999, 163:525-532.
23. Bonifacio E., Hummel M., Walter M., Schmid S., Ziegler A.G. IDDM1 and multiple family history of type 1 diabetes combine to identify neonates at high risk for type 1 diabetes. Diabetes Care 2004, 27:2695-2700.
24. Bonifacio E., Pflüger M., Marienfeld S., Winkler C., Hummel M., Ziegler A.G. Maternal type 1 diabetes reduces the risk of islet autoantibodies: Relationships with birthweight and maternal HbA(1c). Diabetologia 2008, 51:1245-1252.
25. Bottazzo G.F., Bosi E., Cull C.A., Bonifacio E., Locatelli M., Zimmet P., Mackay I.R., Holman R.R. IA-2 antibody prevalence and risk assessment of early insulin requirement in subjects presenting with type 2 diabetes (UKPDS 71). Diabetologia 2005, 48:703-708.
26. Bottini N., Musumeci L., Alonso A., Rahmouni S., Nika K., Rostamkhani M., MacMurray J., Meloni G.F., Lucarelli P., Pellecchia M., et al. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat. Genet. 2004, 36:337-338.
27. Brusko T., Wasserfall C., McGrail K., Schatz R., Viener H.L., Schatz D., Haller M., Rockell J., Gottlieb P., Clare-Salzler M., Atkinson M. No alterations in the frequency of FOXP3+ regulatory T-cells in type 1 diabetes. Diabetes 2007, 56:604-612.
28. Castaño L., Ziegler A.G., Ziegler R., Shoelson S., Eisenbarth G.S. Characterization of insulin autoantibodies in relatives of patients with type I diabetes. Diabetes 1993, 42:1202-1209.
29. Chaussabel D., Quinn C., Shen J., Patel P., Glaser C., Baldwin N., Stichweh D., Blankenship D., Li L., Munagala I., et al. A modular analysis framework for blood genomics studies: Application to systemic lupus erythematosus. Immunity 2008, 29:150-164.
30. Concannon P., Rich S.S., Nepom G.T. Genetics of type 1A diabetes. N. Engl. J. Med. 2009, 360:1646-1654.
31. Dabelea D., Bell R.A., D'Agostino R.B., Imperatore G., Johansen J.M., Linder B., Liu L.L., Loots B., Marcovina S., Mayer-Davis E.J., et al. Incidence of diabetes in youth in the United States. JAMA 2007, 297:2716-2724. Writing Group for the SEARCH for Diabetes in Youth Study Group.
32. Danke N.A., Yang J., Greenbaum C., Kwok W.W. Comparative study of GAD65-specific CD4+ T cells in healthy and type 1 diabetic subjects. J. Autoimmun. 2005, 25:303-311.
33. Durinovic-Belló I., Boehm B.O., Ziegler A.G. Predominantly recognized proinsulin T helper cell epitopes in individuals with and without islet cell autoimmunity. J. Autoimmun. 2002, 18:55-66.
34. Durinovic-Belló I., Wu R.P., Gersuk V.H., Sanda S., Shilling H.G., Nepom G.T. Insulin gene VNTR genotype associates with frequency and phenotype of the autoimmune response to proinsulin. Genes Immun. 2010, 11:188-193.
35. Emery L.M., Babu S., Bugawan T.L., Norris J.M., Erlich H.A., Eisenbarth G.S., Rewers M. Newborn HLA-DR,DQ genotype screening: Age- and ethnicity-specific type 1 diabetes risk estimates. Pediatr. Diabetes 2005, 6:136-144.
36. Fourlanos S., Narendran P., Byrnes G.B., Colman P.G., Harrison L.C. Insulin resistance is a risk factor for progression to type 1 diabetes. Diabetologia 2004, 47:1661-1667.
37. Graham J., Hagopian W.A., Kockum I., Li L.S., Sanjeevi C.B., Lowe R.M., Schaefer J.B., Zarghami M., Day H.L., Landin-Olsson M., et al. Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes. Diabetes 2002, 51:1346-1355. Diabetes Incidence in Sweden Study Group, Swedish Childhood Diabetes Study GroupSwedish Childhood Diabetes Study Group.
38. Grant J., Bourcier K., Wallace S., Pan D., Conway A., Seyfert-Margolis V., Wallace P.K. Validated protocol for FoxP3 reveals increased expression in type 1 diabetes patients. Cytometry B Clin. Cytom. 2009, 76:69-78.
39. Hagopian W.A., Lernmark A., Rewers M.J., Simell O.G., She J.X., Ziegler A.G., Krischer J.P., Akolkar B. TEDDY-The Environmental Determinants of Diabetes in the Young: An observational clinical trial. Ann. N Y Acad. Sci. 2006, 1079:320-326.
40. Harley J.B., Alarcón-Riquelme M.E., Criswell L.A., Jacob C.O., Kimberly R.P., Moser K.L., Tsao B.P., Vyse T.J., Langefeld C.D., Nath S.K., et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat. Genet. 2008, 40:204-210. International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN).
41. Hemminki K., Li X., Sundquist J., Sundquist K. Familial association between type 1 diabetes and other autoimmune and related diseases. Diabetologia 2009, 52:1820-1828.
42. Hummel M., Bonifacio E., Schmid S., Walter M., Knopff A., Ziegler A.G. Brief communication: Early appearance of islet autoantibodies predicts childhood type 1 diabetes in offspring of diabetic parents. Ann. Intern. Med. 2004, 140:882-886.
43. Jackson A., McWilliams C., Kaizer E., Chaussabel D., Glaser C., Noguchi H., Matsumoto S., Levy M.F., Naziruddin B. Gene expression profiling of human pancreatic islets undergoing a simulated process of instant blood-mediated inflammatory reaction. Transplant. Proc. 2008, 40:430-432.
44. Jin Y., Chen X., Podolsky R., Hopkins D., Makala L.H., Muir A., She J.X. APC dysfunction is correlated with defective suppression of T cell proliferation in human type 1 diabetes. Clin. Immunol. 2009, 130:272-279.
45. Kulmala P., Savola K., Petersen J.S., Vähäsalo P., Karjalainen J., Löppönen T., Dyrberg T., Akerblom H.K., Knip M. Prediction of insulin-dependent diabetes mellitus in siblings of children with diabetes. A population-based study. J. Clin. Invest. 1998, 101:327-336. The Childhood Diabetes in Finland Study Group.
46. Kyogoku C., Langefeld C.D., Ortmann W.A., Lee A., Selby S., Carlton V.E., Chang M., Ramos P., Baechler E.C., Batliwalla F.M., et al. Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am. J. Hum. Genet. 2004, 75:504-507.
47. Ladner M.B., Bottini N., Valdes A.M., Noble J.A. Association of the single nucleotide polymorphism C1858T of the PTPN22 gene with type 1 diabetes. Hum. Immunol. 2005, 66:60-64.
48. LaGasse J.M., Brantley M.S., Leech N.J., Rowe R.E., Monks S., Palmer J.P., Nepom G.T., McCulloch D.K., Hagopian W.A. Successful prospective prediction of type 1 diabetes in schoolchildren through multiple defined autoantibodies: An 8-year follow-up of the Washington State Diabetes Prediction Study. Diabetes Care 2002, 25:505-511. Washington State Diabetes Prediction Study.
49. Lambert A.P., Gillespie K.M., Thomson G., Cordell H.J., Todd J.A., Gale E.A., Bingley P.J. Absolute risk of childhood-onset type 1 diabetes defined by human leukocyte antigen class II genotype: A population-based study in the United Kingdom. J. Clin. Endocrinol. Metab. 2004, 89:4037-4043.
50. Lampasona V., Petrone A., Tiberti C., Capizzi M., Spoletini M., di Pietro S., Songini M., Bonicchio S., Giorgino F., Bonifacio E., et al. Zinc transporter 8 antibodies complement GAD and IA-2 antibodies in the identification and characterization of adult-onset autoimmune diabetes: Non Insulin Requiring Autoimmune Diabetes (NIRAD) 4. Diabetes Care 2010, 33:104-108. Non Insulin Requiring Autoimmune Diabetes (NIRAD) Study Group.
51. Lawson J.M., Tremble J., Dayan C., Beyan H., Leslie R.D., Peakman M., Tree T.I. Increased resistance to CD4+CD25hi regulatory T cell-mediated suppression in patients with type 1 diabetes. Clin. Exp. Immunol. 2008, 154:353-359.
52. Lindley S., Dayan C.M., Bishop A., Roep B.O., Peakman M., Tree T.I. Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes. Diabetes 2005, 54:92-99.
53. Link M., Salur L., Kisand K., Rajasalu T., Tillmann V., Uibo R. Higher FoxP3 mRNA expression in peripheral blood mononuclear cells of GAD65 or IA-2 autoantibody-positive compared with autoantibody-negative persons. APMIS 2008, 116:896-902.
54. Long S.A., Walker M.R., Rieck M., James E., Kwok W.W., Sanda S., Pihoker C., Greenbaum C., Nepom G.T., Buckner J.H. Functional islet-specific Treg can be generated from CD4+CD25- T cells of healthy and type 1 diabetic subjects. Eur. J. Immunol. 2009, 39:612-620.
55. Long S.A., Cerosaletti K., Bollyky P.L., Tatum M., Shilling H., Zhang S., Zhang Z.Y., Pihoker C., Sanda S., Greenbaum C., Buckner J.H. Defects in IL-2R signaling contribute to diminished maintenance of FOXP3 expression in CD4(+)CD25(+) regulatory T-cells of type 1 diabetic subjects. Diabetes 2010, 59:407-415.
56. Lu J., Li Q., Xie H., Chen Z.J., Borovitskaya A.E., Maclaren N.K., Notkins A.L., Lan M.S. Identification of a second transmembrane protein tyrosine phosphatase, IA-2beta, as an autoantigen in insulin-dependent diabetes mellitus: Precursor of the 37-kDa tryptic fragment. Proc. Natl. Acad. Sci. USA 1996, 93:2307-2311.
57. Luczyński W., Stasiak-Barmuta A., Urban R., Urban M., Florys B., Hryszko M. Lower percentages of T regulatory cells in children with type 1 diabetes - preliminary report. Pediatr Endocrinol Diabetes Metab 2009, 15:34-38.
58. Mayr A., Schlosser M., Grober N., Kenk H., Ziegler A.G., Bonifacio E., Achenbach P. GAD autoantibody affinity and epitope specificity identify distinct immunization profiles in children at risk for type 1 diabetes. Diabetes 2007, 56:1527-1533.
59. Monti P., Scirpoli M., Rigamonti A., Mayr A., Jaeger A., Bonfanti R., Chiumello G., Ziegler A.G., Bonifacio E. Evidence for in vivo primed and expanded autoreactive T cells as a specific feature of patients with type 1 diabetes. J. Immunol. 2007, 179:5785-5792.
60. Monti P., Scirpoli M., Maffi P., Piemonti L., Secchi A., Bonifacio E., Roncarolo M.G., Battaglia M. Rapamycin monotherapy in patients with type 1 diabetes modifies CD4+CD25+FOXP3+ regulatory T-cells. Diabetes 2008, 57:2341-2347.
61. Muraro P.A., Pette M., Bielekova B., McFarland H.F., Martin R. Human autoreactive CD4+ T cells from naive CD45RA+ and memory CD45RO+ subsets differ with respect to epitope specificity and functional antigen avidity. J. Immunol. 2000, 164:5474-5481.
62. Naserke H.E., Bonifacio E., Ziegler A.G. Immunoglobulin G insulin autoantibodies in BABYDIAB offspring appear postnatally: Sensitive early detection using a protein A/G-based radiobinding assay. J. Clin. Endocrinol. Metab. 1999, 84:1239-1243.
63. Naserke H.E., Bonifacio E., Ziegler A.G. Prevalence, characteristics and diabetes risk associated with transient maternally acquired islet antibodies and persistent islet antibodies in offspring of parents with type 1 diabetes. J. Clin. Endocrinol. Metab. 2001, 86:4826-4833.
64. Oling V., Marttila J., Knip M., Simell O., Ilonen J. Circulating CD4+CD25 high regulatory T cells and natural killer T cells in children with newly diagnosed type 1 diabetes or with diabetes-associated autoantibodies. Ann. N Y Acad. Sci. 2007, 1107:363-372.
65. Onengut-Gumuscu S., Ewens K.G., Spielman R.S., Concannon P. A functional polymorphism (1858C/T) in the PTPN22 gene is linked and associated with type I diabetes in multiplex families. Genes Immun. 2004, 5:678-680.
66. Oresic M., Simell S., Sysi-Aho M., Näntö-Salonen K., Seppänen-Laakso T., Parikka V., Katajamaa M., Hekkala A., Mattila I., Keskinen P., et al. Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes. J. Exp. Med. 2008, 205:2975-2984.
67. Palmer J.P., Asplin C.M., Clemons P., Lyen K., Tatpati O., Raghu P.K., Paquette T.L. Insulin antibodies in insulin-dependent diabetics before insulin treatment. Science 1983, 222:1337-1339.
68. Pascual V., Allantaz F., Patel P., Palucka A.K., Chaussabel D., Banchereau J. How the study of children with rheumatic diseases identified interferon-alpha and interleukin-1 as novel therapeutic targets. Immunol. Rev. 2008, 223:39-59.
69. *0602 is associated with dominant protection from diabetes even among islet cell antibody-positive first-degree relatives of patients with IDDM. Diabetes 1995, 44:608-613.
70. Pugliese A., Zeller M., Fernandez A., Zalcberg L.J., Bartlett R.J., Ricordi C., Pietropaolo M., Eisenbarth G.S., Bennett S.T., Patel D.D. The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes. Nat. Genet. 1997, 15:293-297.
71. Putnam A.L., Vendrame F., Dotta F., Gottlieb P.A. CD4+CD25high regulatory T cells in human autoimmune diabetes. J. Autoimmun. 2005, 24:55-62.
72. Putnam A.L., Brusko T.M., Lee M.R., Liu W., Szot G.L., Ghosh T., Atkinson M.A., Bluestone J.A. Expansion of human regulatory T-cells from patients with type 1 diabetes. Diabetes 2009, 58:652-662.
73. Rabin D.U., Pleasic S.M., Shapiro J.A., Yoo-Warren H., Oles J., Hicks J.M., Goldstein D.E., Rae P.M. Islet cell antigen 512 is a diabetes-specific islet autoantigen related to protein tyrosine phosphatases. J. Immunol. 1994, 152:3183-3188.
74. Redondo M.J., Jeffrey J., Fain P.R., Eisenbarth G.S., Orban T. Concordance for islet autoimmunity among monozygotic twins. N. Engl. J. Med. 2008, 359:2849-2850.
75. Rieck M., Arechiga A., Onengut-Gumuscu S., Greenbaum C., Concannon P., Buckner J.H. Genetic variation in PTPN22 corresponds to altered function of T and B lymphocytes. J. Immunol. 2007, 179:4704-4710.
76. Rubio-Cabezas O., Minton J.A., Caswell R., Shield J.P., Deiss D., Sumnik Z., Cayssials A., Herr M., Loew A., Lewis V., et al. Clinical heterogeneity in patients with FOXP3 mutations presenting with permanent neonatal diabetes. Diabetes Care 2009, 32:111-116.
77. Ryden A., Stechova K., Durilova M., Faresjö M. Switch from a dominant Th1-associated immune profile during the pre-diabetic phase in favour of a temporary increase of a Th3-associated and inflammatory immune profile at the onset of type 1 diabetes. Diabetes Metab. Res. Rev. 2009, 25:335-343.
78. Sanjeevi C.B., Landin-Olsson M., Kockum I., Dahlquist G., Lernmark A. Effects of the second HLA-DQ haplotype on the association with childhood insulin-dependent diabetes mellitus. Tissue Antigens 1995, 45:148-152.
79. Schenker M., Hummel M., Ferber K., Walter M., Keller E., Albert E.D., Janka H.U., Kastendiek C., Sorger M., Louwen F., Ziegler A.G. Early expression and high prevalence of islet autoantibodies for DR3/4 heterozygous and DR4/4 homozygous offspring of parents with Type I diabetes: The German BABYDIAB study. Diabetologia 1999, 42:671-677.
80. Schneider A., Rieck M., Sanda S., Pihoker C., Greenbaum C., Buckner J.H. The effector T cells of diabetic subjects are resistant to regulation via CD4+ FOXP3+ regulatory T cells. J. Immunol. 2008, 181:7350-7355.
81. Smyth D., Cooper J.D., Collins J.E., Heward J.M., Franklyn J.A., Howson J.M., Vella A., Nutland S., Rance H.E., Maier L., et al. Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus. Diabetes 2004, 53:3020-3023.
82. Srikanta S., Ganda O.P., Rabizadeh A., Soeldner J.S., Eisenbarth G.S. First-degree relatives of patients with type I diabetes mellitus. Islet-cell antibodies and abnormal insulin secretion. N. Engl. J. Med. 1985, 313:461-464.
83. Standifer N.E., Burwell E.A., Gersuk V.H., Greenbaum C.J., Nepom G.T. Changes in autoreactive T cell avidity during type 1 diabetes development. Clin. Immunol. 2009, 132:312-320.
84. Tree T.I., Roep B.O., Peakman M. A mini meta-analysis of studies on CD4+CD25+ T cells in human type 1 diabetes: Report of the Immunology of Diabetes Society T Cell Workshop. Ann. N Y Acad. Sci. 2006, 1079:9-18.
85. Turunen J.A., Wessman M., Forsblom C., Kilpikari R., Parkkonen M., Pöntynen N., Ilmarinen T., Ulmanen I., Peltonen L., Groop P.H. Association analysis of the AIRE and insulin genes in Finnish type 1 diabetic patients. Immunogenetics 2006, 58:331-338.
86. Vafiadis P., Bennett S.T., Todd J.A., Nadeau J., Grabs R., Goodyer C.G., Wickramasinghe S., Colle E., Polychronakos C. Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus. Nat. Genet. 1997, 15:289-292.
87. Vang T., Congia M., Macis M.D., Musumeci L., Orrú V., Zavattari P., Nika K., Tautz L., Taskén K., Cucca F., et al. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat. Genet. 2005, 37:1317-1319.
88. Velaga M.R., Wilson V., Jennings C.E., Owen C.J., Herington S., Donaldson P.T., Ball S.G., James R.A., Quinton R., Perros P., Pearce S.H. The codon 620 tryptophan allele of the lymphoid tyrosine phosphatase (LYP) gene is a major determinant of Graves' disease. J. Clin. Endocrinol. Metab. 2004, 89:5862-5865.
89. Verge C.F., Gianani R., Kawasaki E., Yu L., Pietropaolo M., Jackson R.A., Chase H.P., Eisenbarth G.S. Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes 1996, 45:926-933.
90. Vrabelova Z., Hrotekova Z., Hladikova Z., Bohmova K., Stechova K., Michalek J. CD 127- and FoxP3+ expression on CD25+CD4+ T regulatory cells upon specific diabetogeneic stimulation in high-risk relatives of type 1 diabetes mellitus patients. Scand. J. Immunol. 2008, 67:404-410.
91. Wang X., Jia S., Geoffrey R., Alemzadeh R., Ghosh S., Hessner M.J. Identification of a molecular signature in human type 1 diabetes mellitus using serum and functional genomics. J. Immunol. 2008, 180:1929-1937.
92. Wenzlau J.M., Juhl K., Yu L., Moua O., Sarkar S.A., Gottlieb P., Rewers M., Eisenbarth G.S., Jensen J., Davidson H.W., Hutton J.C. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc. Natl. Acad. Sci. USA 2007, 104:17040-17045.
93. Wildin R.S., Ramsdell F., Peake J., Faravelli F., Casanova J.L., Buist N., Levy-Lahad E., Mazzella M., Goulet O., Perroni L., et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat. Genet. 2001, 27:18-20.
94. Yang Z., Zhou Z., Huang G., Ling H., Yan X., Peng J., Li X. The CD4(+) regulatory T-cells is decreased in adults with latent autoimmune diabetes. Diabetes Res. Clin. Pract. 2007, 76:126-131.
95. Yang J., Danke N., Roti M., Huston L., Greenbaum C., Pihoker C., James E., Kwok W.W. CD4+ T cells from type 1 diabetic and healthy subjects exhibit different thresholds of activation to a naturally processed proinsulin epitope. J. Autoimmun. 2008, 31:30-41.
96. Yu J., Yu L., Bugawan T.L., Erlich H.A., Barriga K., Hoffman M., Rewers M., Eisenbarth G.S. Transient antiislet autoantibodies: Infrequent occurrence and lack of association with " genetic" risk factors. J. Clin. Endocrinol. Metab. 2000, 85:2421-2428.
97. Ziegler A.G., Standl E., Albert E., Mehnert H. HLA-associated insulin autoantibody formation in newly diagnosed type I diabetic patients. Diabetes 1991, 40:1146-1149.
98. Ziegler A.G., Hummel M., Schenker M., Bonifacio E. Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: The 2-year analysis of the German BABYDIAB Study. Diabetes 1999, 48:460-468.