Proof-of-concept, randomized, controlled clinical trial of bacillus-calmette-guerin for treatment of long-term type 1 diabetes

PLoS ONE

Volumn 7, Issue 8, 2012, Pages

  Faustman, Denise L ^a   Wang, Limei ^a   Okubo, Yoshiaki ^a   Burger, Douglas ^a   Ban, Liqin ^a   Man, Guotong ^a   Zheng, Hui ^a   Schoenfeld, David ^a   Pompei, Richard ^a   Avruch, Joseph ^a   Nathan, David M ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BCG VACCINE; C PEPTIDE; GLUTAMATE DECARBOXYLASE; INSULIN; PLACEBO; THERACYS; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG;

ADULT; ARTICLE; AUTOIMMUNITY; BLOOD SAMPLING; CONTROLLED STUDY; DISEASE ASSOCIATION; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; EPSTEIN BARR VIRUS INFECTION; FEMALE; HUMAN; HUMAN CELL; INNATE IMMUNITY; INSULIN BLOOD LEVEL; INSULIN DEPENDENT DIABETES MELLITUS; LONG TERM CARE; MAJOR CLINICAL STUDY; MALE; OUTCOME ASSESSMENT; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; REGULATORY T LYMPHOCYTE; UNITED STATES;

ADULT; AUTOANTIBODIES; AUTOIMMUNITY; BCG VACCINE; BIOLOGICAL MARKERS; C-PEPTIDE; CASE-CONTROL STUDIES; DIABETES MELLITUS, TYPE 1; DOUBLE-BLIND METHOD; FEMALE; GLUTAMATE DECARBOXYLASE; HERPESVIRUS 4, HUMAN; HUMANS; INSULIN-SECRETING CELLS; MALE; MIDDLE AGED; PLACEBOS; T-LYMPHOCYTES; TUMOR NECROSIS FACTOR-ALPHA;

HUMAN HERPESVIRUS 4; MYCOBACTERIUM BOVIS BCG; RODENTIA;

EID: 84864692611     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0041756     Document Type: Article

References (56)

1. Kodama S, Davis M, Faustman DL, (2005) The therapeutic potential of tumor necrosis factor for autoimmune disease: a mechanistically based hypothesis. Cell Mol Life Sci 62: 1850-1862.
2. Satoh J, Seino H, Abo T, (1989) Recombinant human tumor necrosis factor a suppresses autoimmune diabetes in nonobese diabetic mice. J Clin Invest 84: 1345-1348.
3. Grewal IS, Grewal KD, Wong FS, Picarella DE, Janeway CA, et al. (1996) Local expression of transgene encoded TNF alpha in islets prevents autoimmune diabetes in non-obese diabetic (NOD) mice by preventing the development of autoreactive islet specific T cells. J Exp Med 184: 1963-1974.
4. Ban L, Zhang J, Wang L, Kuhtreiber W, Burger D, et al. (2008) Selective death of autoreactive T cells in human diabetes by TNF or TNF receptor 2 agonism. Proc Natl Acad Sci U S A 105: 13644-13649.
5. Qin HY, Chaturvedi P, Singh B, (2004) In vivo apoptosis of diabetogenic T cells in NOD mice by IFN-γ/TNF-α. Int Immunol 16: 1723-1732.
6. Christen U, Von Herrath MG, (2002) Apoptosis of autoreactive CD8 lymphocytes as a potential mechanism for the abrogation of type 1 diabetes by islet-specific TNF-alpha expression at a time when the autoimmune process is already ongoing. Ann N Y Acad Sci 958: 166-169.
7. Ryu S, Kodama S, Ryu K, Schoenfeld DA, Faustman DL, (2001) Reversal of established autoimmune diabetes by restoration of endogenous beta cell function. J Clin Invest 108: 63-72.
8. Kodama S, Kuhtreiber W, Fujimura S, Dale EA, Faustman DL, (2003) Islet regeneration during the reversal of autoimmune diabetes in NOD mice. Science 302: 1223-1227.
9. Rahman MM, McFadden G, (2006) Modulation of tumor necrosis factor by microbial pathogens. PLoS Pathog 2: e4.
10. Harada M, Kishimoto Y, Makino S, (1990) Prevention of overt diabetes and insulitis in NOD mice by a single BCG vaccination. Diabetes Res Clin Prac 8: 85-89.
11. Sadelain MWJ, Hui-Yu Q, Lauzon J, Singh B, (1990) Prevention of type I diabetes in NOD mice by adjuvant immunotherapy. Diabetes 39: 583-589.
12. McInerney MF, Pek SB, Thomas DW, (1991) Prevention of insulitis and diabetes onset by treatment with complete Freund's adjuvant in NOD mice. Diabetes 40: 715-725.
13. Shehadeh N, Calcinaro F, Bradley BJ, Bruchlim I, Vardi P, et al. (1994) Effect of adjuvant therapy on development of diabetes in mouse and man [see comments]. Lancet 343: 706-707.
14. Burger DE, Wang L, Ban L, Okubo Y, Kuhtreiber WM, et al. (2011) Novel automated blood separations validate whole cell biomarkers. PLoS One 6: e22430.
15. Pinkse GG, Tysma OH, Bergen CA, Kester MG, Ossendorp F, et al. (2005) Autoreactive CD8 T cells associated with beta cell destruction in type 1 diabetes. Proc Natl Acad Sci U S A 102: 18425-18430.
16. Achenbach P, Lampasona V, Landherr U, Koczwara K, Krause S, et al. (2009) Autoantibodies to zinc transporter 8 and SLC30A8 genotype stratify type 1 diabetes risk. Diabetologia 52: 1881-1888.
17. Castiblanco J, Anaya J-M, (2008) The I kappa BL gene polymorphism influences risk of acquiring systemic lupus erythematosus and Sjogren's syndrome. Human Immunology 69: 45-51.
18. Trials CoSfS-N-PCR, Policy BoHS (2001) Small Clinical Trials: Issues and Challenges: The National Academies Press.
19. Devergne O, Hatzivassiliou E, Izumi KM, Kaye KM, Kleijnen MF, et al. (1996) Association of TRAF1, TRAF2, and TRAF3 with an Epstein-Barr virus LMP1 domain important for B-lymphocyte transformation: role in NF-kappaB activation. Mol Cell Biol 16: 7098-7108.
20. Sanjeevi CB, Das AK, Shtauvere-Brameus A, (2002) BCG vaccination and GAD65 and IA-2 autoantibodies in autoimmune diabetes in southern India. Ann N Y Acad Sci 958: 293-296.
21. Braghi S, Bonifacio E, Secchi A, Di Carlo V, Pozza G, et al. (2000) Modulation of humoral islet autoimmunity by pancreas allotransplantation influences allograft outcome in patients with type 1 diabetes. Diabetes 49: 218-224.
22. Bosi E, Braghi S, Maffi P, Scirpoli M, Bertuzzi F, et al. (2001) Autoantibody response to islet transplantation in type 1 diabetes. Diabetes 50: 2464-2471.
23. Pozzilli P, (1997) BCG vaccine in insulin-dependent diabetes mellitus. IMDIAB Group. Lancet 349: 1520-1521.
24. Allen HF, Klingensmith GJ, Jensen P, Simoes E, Hayward A, et al. (1999) Effect of Bacillus Calmette-Guerin vaccination on new-onset type 1 diabetes. A randomized clinical study. Diabetes Care 22: 1703-1707.
25. Elliott JF, Marlin KL, Couch RM, (1998) Effect of bacille Calmette-Guerin vaccination on C-peptide secretion in children newly diagnosed with IDDM. Diabetes Care 21: 1691-1693.
26. Ristori G, Buzzi MG, Sabatini U, Giugni E, Bastianello S, et al. (1999) Use of Bacille Calmette-Guerin (BCG) in multiple sclerosis. Neurology 53: 1588-1589.
27. Paolillo A, Buzzi MG, Giugni E, Sabatini U, Bastianello S, et al. (2003) The effect of Bacille Calmette-Guerin on the evolution of new enhancing lesions to hypointense T1 lesions in relapsing remitting MS. Journal of Neurology 250: 247-248.
28. Khan M, Aydin M, (2012) Effect of BCG vaccine in the prevention of type 1 diabetes mellitus. Contemp J Med 2: 1-8.
29. Sadelain MW, Qin HY, Sumoski W, Parfrey N, Singh B, et al. (1990) Prevention of diabetes in the BB rat by early immunotherapy using Freund's adjuvant. Journal of Autoimmunity 3: 671-680.
30. Okubo Y, Kanazawa Y, Oikawa Y, Miyazaki JI, Shimada A, (2006) Islet hypertrophy observed in "reversed". diabetic NOD mouse after pancreatic beta cell line administration Diabetes A 281: 1193.
31. Enayati PJ, Papadakis KA, (2005) Association of Anti-tumor Necrosis Factor Therapy With the Development of Multiple Sclerosis. J Clin Gastroenterol 39: 303-306.
32. Sicotte NL, Voskuhl RR, (2001) Onset of multiple sclerosis associated with anti-TNF therapy. Neurology 57: 1885-1888.
33. Thomas CW Jr, Weinshenker BG, Sandborn WJ, (2004) Demyelination during anti-tumor necrosis factor alpha therapy with infliximab for Crohn's disease. Inflamm Bowel Dis 10: 28-31.
34. van Oosten BW, Barkhof F, Truyen L, Boringa JB, Bertelsmann FW, et al. (1996) Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology 47: 1531-1534.
35. Boulton JG, Bourne JT, (2007) Unstable diabetes in a patient receiving anti-TNF-alpha for rheumatoid arthritis. Rheumatology 46: 178-179.
36. Ramos-Casals M, Brito-Zeron P, Soto MJ, Cuadrado MJ, Khamashta MA, (2008) Autoimmune diseases induced by TNF-targeted therapies. Best Practice & Research in Clinical Rheumatology 22: 847-861.
37. Ko JM, Gottlieb AB, Kerbleski JF, (2009) Induction and exacerbation of psoriasis with TNF-blockade therapy: A review and analysis of 127 cases. Journal of Dermatological Treatment 20: 100-108.
38. Hayashi T, Faustman D, (1999) NOD mice are defective in proteasome production and activation of NF- kappaB. Mol Cell Biol 19: 8646-8659.
39. Hayashi T, Faustman DL, (2001) Selected contribution: Association of gender-related LMP2 inactivation with autoimmune pathogenesis. J Appl Physiol 91: 2804-2815.
40. Hayashi T, Kodama S, Faustman DL, (2000) Reply to 'LMP2 expression and proteasome activity in NOD mice'. Nat Med 6: 1065-1066.
41. Guo D, Li M, Zhang Y, Yang P, Eckenrode S, et al. (2004) A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes. Nat Genet 36: 837-841.
42. Wong HK, Kammer GM, Dennis G, Tsokos GC, (1999) Abnormal NF-kappa B activity in T lymphocytes from patients with systemic lupus erythematosus is associated with decreased p65-RelA protein expression. J Immunol 163: 1682-1689.
43. Kessel A, Rosner I, Rozenbaum M, Zisman D, Sagiv A, et al. (2004) Increased CD8+ T cell apoptosis in scleroderma is associated with low levels of NF-kappa B. J Clin Immunol. 24: 30-36.
44. Valero R, Baron ML, Guerin S, Beliard S, Lelouard H, et al. (2002) A defective NF-kappa B/RelB pathway in autoimmune-prone New Zealand black mice is associated with inefficient expansion of thymocyte and dendritic cells. J Immunol 169: 185-192.
45. Zaiss DMW, Bekker CPJ, Grone A, Lie BA, Sijts AJAM, (2011) Proteasome Immunosubunits Protect against the Development of CD8 T Cell-Mediated Autoimmune Diseases. Journal of Immunology 187: 2302-2309.
46. Bohren KM, Nadkarni V, Song JH, Gabbay KH, Owerbach D, (2004) A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus. J Biol Chem 279: 27233-27238.
47. Vereecke L, Beyaert R, van Loo G, (2009) The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology. Trends in Immunology 30: 383-391.
48. Trynka G, Zhernakova A, Romanos J, Franke L, Hunt KA, et al. (2009) Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappa B signalling. Gut 58: 1078-1083.
49. Zhang G-L, Zou Y-F, Feng X-L, Shi H-J, Du X-F, et al. (2011) Association of the NFKBIA gene polymorphisms with susceptibility to autoimmune and inflammatory diseases: a meta-analysis. Inflammation Research 60: 11-18.
50. Till A, Rosenstiel P, Krippner-Heidenreich A, Mascheretti-Croucher S, Croucher PJ, et al. (2005) The Met-196-> Arg variation of human tumor necrosis factor receptor 2 (TNFR2) affects TNF-alpha-induced apoptosis by impaired NF-kappaB signaling and target gene expression. J Biol Chem 280: 5994-6004.
51. Allcock RJN, de la Concha EG, Fernandez-Arquero M, Vigil P, Conejero L, et al. (1999) Susceptibility to multiple sclerosis mediated by HLA-DRB1 is influenced by a second gene telomeric of the TNF cluster. Human Immunology 60: 1266-1273.
52. Allcock RJN, Christiansen FT, Price P, (1999) The central MHC gene IKBL carries a structural polymorphism that is associated with HLA-A3,B7,DR15. Immunogenetics 49: 660-665.
53. Miterski B, Bohringer S, Klein W, Sindern E, Haupts M, et al. (2002) Inhibitors in the NFkappaB cascade comprise prime candidate genes predisposing to multiple sclerosis, especially in selected combinations. Genes Immun 3: 211-219.
54. Wandinger KP, Sturzebecher CS, Bielekova B, Detore G, Rosenwald A, et al. (2001) Complex immunomodulatory effects of interferon-beta in multiple sclerosis include the upregulation of T helper 1-associated marker genes. Annals of Neurology 50: 349-357.
55. Fu Y, Yan G, Shi L, Faustman D, (1998) Antigen processing and autoimmunity. Evaluation of mRNA abundance and function of HLA-linked genes. Annals of the New York Academy of Sciences 842: 138-155.
56. Steffes MW, Sibley S, Jackson M, Thomas W, (2003) Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care 26: 832-836.