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Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial


Frank Waldron-Lynch and colleagues investigate immune cell biomarker responses in patients with type 1 diabetes following a single dose of recombinant interleukin-2.


Vyšlo v časopise: Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial. PLoS Med 13(10): e32767. doi:10.1371/journal.pmed.1002139
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1002139

Souhrn

Frank Waldron-Lynch and colleagues investigate immune cell biomarker responses in patients with type 1 diabetes following a single dose of recombinant interleukin-2.


Zdroje

1. Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet. 2014;383:69–82. doi: 10.1016/S0140-6736(13)60591-7 23890997

2. McKnight JA, Wild SH, Lamb MJ, Cooper MN, Jones TW, Davis EA, et al. Glycaemic control of Type 1 diabetes in clinical practice early in the 21st century: an international comparison. Diabet Med. 2015;32:1036–1050. doi: 10.1111/dme.12676 25510978

3. Miller KM, Foster NC, Beck RW, Bergenstal RM, DuBose SN, DiMeglio LA, et al. Current state of type 1 diabetes treatment in the U.S.: updated data from the T1D Exchange clinic registry. Diabetes Care. 2015;38:971–978. doi: 10.2337/dc15-0078 25998289

4. Herold KC, Gitelman SE, Willi SM, Gottlieb PA, Waldron-Lynch F, Devine L, et al. Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial. Diabetologia. 2013;56:391–400. doi: 10.1007/s00125-012-2753-4 23086558

5. Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, Becker DJ, Gitelman SE, Goland R, et al. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. N Engl J Med. 2009;361:2143–2152. doi: 10.1056/NEJMoa0904452 19940299

6. Keymeulen B, Vandemeulebroucke E, Ziegler AG, Mathieu C, Kaufman L, Hale G, et al. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med. 2005;352:2598–2608. doi: 10.1056/NEJMoa043980 15972866

7. Rigby MR, Harris KM, Pinckney A, DiMeglio LA, Rendell MS, Felner EI, et al. Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients. J Clin Invest. 2015;125:3285–3296. doi: 10.1172/JCI81722 26193635

8. Orban T, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, et al. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet. 2011;378:412–419. doi: 10.1016/S0140-6736(11)60886-6 21719096

9. Nelson MR, Tipney H, Painter JL, Shen J, Nicoletti P, Shen Y, et al. The support of human genetic evidence for approved drug indications. Nat Genet. 2015;47:856–860. doi: 10.1038/ng.3314 26121088

10. Cho JH, Feldman M. Heterogeneity of autoimmune diseases: pathophysiologic insights from genetics and implications for new therapies. Nat Med. 2015;21:730–738. doi: 10.1038/nm.3897 26121193

11. Todd JA, Aitman TJ, Cornall RJ, Ghosh S, Hall JR, Hearne CM, et al. Genetic analysis of autoimmune type 1 diabetes mellitus in mice. Nature. 1991;351:542–547. doi: 10.1038/351542a0 1675432

12. Yamanouchi J, Rainbow D, Serra P, Howlett S, Hunter K, Garner VE, et al. Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. Nat Genet. 2007;39:329–337. doi: 10.1038/ng1958 17277778

13. Vella A, Cooper JD, Lowe CE, Walker N, Nutland S, Widmer B, et al. Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms. Am J Hum Genet. 2005;76:773–779. doi: 10.1086/429843 15776395

14. Lowe CE, Cooper JD, Brusko T, Walker NM, Smyth DJ, Bailey R, et al. Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes. Nat Genet. 2007;39:1074–1082. doi: 10.1038/ng2102 17676041

15. Todd JA, Walker NM, Cooper JD, Smyth DJ, Downes K, Plagnol V, et al. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet. 2007;39:857–864. doi: 10.1038/ng2068 17554260

16. Dendrou CA, Plagnol V, Fung E, Yang JH, Downes K, Cooper JD, et al. Cell-specific protein phenotypes for the autoimmune locus IL2RA using a genotype-selectable human bioresource. Nat Genet. 2009;41:1011–1015. doi: 10.1038/ng.434 19701192

17. Garg G, Tyler JR, Yang JH, Cutler AJ, Downes K, Pekalski M, et al. Type 1 diabetes-associated IL2RA variation lowers IL-2 signaling and contributes to diminished CD4+CD25+ regulatory T cell function. J Immunol. 2012;188:4644–4653. doi: 10.4049/jimmunol.1100272 22461703

18. Thompson WS, Pekalski ML, Simons HZ, Smyth DJ, Castro-Dopico X, Guo H, et al. Multi-parametric flow cytometric and genetic investigation of the peripheral B cell compartment in human type 1 diabetes. Clin Exp Immunol. 2014;177:571–585. doi: 10.1111/cei.12362 24773525

19. Boyman O, Sprent J. The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol. 2012;12:180–190. doi: 10.1038/nri3156 22343569

20. Liao W, Lin JX, Leonard WJ. Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy. Immunity. 2013;38:13–25. doi: 10.1016/j.immuni.2013.01.004 23352221

21. Liston A, Gray DH. Homeostatic control of regulatory T cell diversity. Nat Rev Immunol. 2014;14:154–165. doi: 10.1038/nri3605 24481337

22. Liu Z, Gerner MY, Van Panhuys N, Levine AG, Rudensky AY, Germain RN. Immune homeostasis enforced by co-localized effector and regulatory T cells. Nature. 2015;528:225–230. doi: 10.1038/nature16169 26605524

23. Setoguchi R, Hori S, Takahashi T, Sakaguchi S. Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J Exp Med. 2005;201:723–735. doi: 10.1084/jem.20041982 15753206

24. Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999;17:2105–2116. 10561265

25. Negrier S, Escudier B, Lasset C, Douillard JY, Savary J, Chevreau C, et al. Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Français d’Immunothérapie. N Engl J Med. 1998;338:1272–1278. doi: 10.1056/NEJM199804303381805 9562581

26. Sim GC, Martin-Orozco N, Jin L, Yang Y, Wu S, Washington E, et al. IL-2 therapy promotes suppressive ICOS+ Treg expansion in melanoma patients. J Clin Invest. 2014;124:99–110. doi: 10.1172/JCI46266 24292706

27. Tang Q, Adams JY, Penaranda C, Melli K, Piaggio E, Sgouroudis E, et al. Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity. 2008;28:687–697. doi: 10.1016/j.immuni.2008.03.016 18468463

28. Grinberg-Bleyer Y, Baeyens A, You S, Elhage R, Fourcade G, Gregoire S, et al. IL-2 reverses established type 1 diabetes in NOD mice by a local effect on pancreatic regulatory T cells. J Exp Med. 2010;207:1871–1878. doi: 10.1084/jem.20100209 20679400

29. Koreth J, Matsuoka K, Kim HT, McDonough SM, Bindra B, Alyea EP, et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011;365:2055–2066. doi: 10.1056/NEJMoa1108188 22129252

30. Koreth J, Kim HT, Jones KT, Lange PB, Reynolds CG, Chammas MJ, et al. Efficacy, durability, and response predictors of low-dose interleukin-2 therapy for chronic graft vs. host disease. Blood. 2016;128:130–137. doi: 10.1182/blood-2016-02-702852 27073224

31. Saadoun D, Rosenzwajg M, Joly F, Six A, Carrat F, Thibault V, et al. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med. 2011;365:2067–2077. doi: 10.1056/NEJMoa1105143 22129253

32. Humrich JY, von Spee-Mayer C, Siegert E, Alexander T, Hiepe F, Radbruch A, et al. Rapid induction of clinical remission by low-dose interleukin-2 in a patient with refractory SLE. Ann Rheum Dis. 2015;74:791–792. doi: 10.1136/annrheumdis-2014-206506 25609413

33. Castela E, Le Duff F, Butori C, Ticchioni M, Hofman P, Bahadoran P, et al. Effects of low-dose recombinant interleukin 2 to promote T-regulatory cells in alopecia areata. JAMA Dermatol. 2014;150:748–751. doi: 10.1001/jamadermatol.2014.504 24872229

34. Long SA, Rieck M, Sanda S, Bollyky JB, Samuels PL, Goland R, et al. Rapamycin/IL-2 combination therapy in patients with type 1 diabetes augments Tregs yet transiently impairs β-cell function. Diabetes. 2012. doi: 10.2337/db12-0049

35. Long SA, Buckner JH, Greenbaum CJ. IL-2 therapy in type 1 diabetes: “Trials” and tribulations. Clin Immunol. 2013;149:324–331. doi: 10.1016/j.clim.2013.02.005 23499139

36. Hartemann A, Bensimon G, Payan CA, Jacqueminet S, Bourron O, Nicolas N, et al. Low-dose interleukin 2 in patients with type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2013;1:295–305. doi: 10.1016/S2213-8587(13)70113-X 24622415

37. Low-dose rhIL-2 in patients with recently-diagnosed type 1 diabetes (DIABIL-2). ClinicalTrials.gov. 2016 Feb 15 [cited 26 Jul 2016]. Available: https://clinicaltrials.gov/ct2/show/NCT02411253.

38. Staeva-Vieira T, Peakman M, von Herrath M. Translational mini-review series on type 1 diabetes: immune-based therapeutic approaches for type 1 diabetes. Clin Exp Immunol. 2007;148:17–31. doi: 10.1111/j.1365-2249.2007.03328.x 17349010

39. Lernmark A, Larsson HE. Immune therapy in type 1 diabetes mellitus. Nat Rev Endocrinol. 2013;9:92–103. doi: 10.1038/nrendo.2012.237 23296174

40. Kenefeck R, Wang CJ, Kapadi T, Wardzinski L, Attridge K, Clough LE, et al. Follicular helper T cell signature in type 1 diabetes. J Clin Invest. 2015;125:292–303. doi: 10.1172/JCI76238 25485678

41. Ferreira RC, Simons HZ, Thompson WS, Cutler AJ, Dopico XC, Smyth DJ, et al. IL-21 production by CD4+ effector T cells and frequency of circulating follicular helper T cells are increased in type 1 diabetes patients. Diabetologia. 2015;58:781–790. doi: 10.1007/s00125-015-3509-8 25652388

42. Waldron-Lynch F, Kareclas P, Irons K, Walker NM, Mander A, Wicker LS, et al. Rationale and study design of the Adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D): a non-randomised, open label, adaptive dose finding trial. BMJ Open. 2014;4:e005559. doi: 10.1136/bmjopen-2014-005559 24898091

43. Yang JH, Cutler AJ, Ferreira RC, Reading JL, Cooper NJ, Wallace C, et al. Natural variation in interleukin-2 sensitivity influences regulatory T-cell frequency and function in individuals with long-standing type 1 diabetes. Diabetes. 2015;64:3891–3902. doi: 10.2337/db15-0516 26224887

44. Rainbow DB, Yang X, Burren O, Pekalski ML, Smyth DJ, Klarqvist MD, et al. Epigenetic analysis of regulatory T cells using multiplex bisulfite sequencing. Eur J Immunol. 2015;45:3200–3203. doi: 10.1002/eji.201545646 26420295

45. Glezer EN, Stengelin M, Aghvanyan A, Nikolenko GN, Roy D, Higgins M, et al. Cytokine immunoassays with sub-fg/ml detection limits. AAPS 2014 National Biotechnology Conference; 19–21 May 2014; San Diego, CA, US.

46. Bell CJ, Sun Y, Nowak UM, Clark J, Howlett S, Pekalski ML, et al. Sustained in vivo signaling by long-lived IL-2 induces prolonged increases of regulatory T cells. J Autoimmun. 2015;56:66–80. doi: 10.1016/j.jaut.2014.10.002 25457307

47. Downes K, Marcovecchio ML, Clarke P, Cooper JD, Ferreira RC, Howson JM, et al. Plasma concentrations of soluble IL-2 receptor α (CD25) are increased in type 1 diabetes and associated with reduced C-peptide levels in young patients. Diabetologia. 2014;57:366–372. doi: 10.1007/s00125-013-3113-8 24264051

48. Heywood J, Evangelou M, Goymer D, Kennet J, Anselmiova K, Guy C, et al. Effective recruitment of participants to a phase I study using the internet and publicity releases through charities and patient organisations: analysis of the adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D). Trials. 2015;16:86. doi: 10.1186/s13063-015-0583-7 25881192

49. Konrad MW, Hemstreet G, Hersh EM, Mansell PW, Mertelsmann R, Kolitz JE, et al. Pharmacokinetics of recombinant interleukin 2 in humans. Cancer Res. 1990;50:2009–2017. 2317789

50. Duhen T, Duhen R, Lanzavecchia A, Sallusto F, Campbell DJ. Functionally distinct subsets of human FOXP3+ Treg cells that phenotypically mirror effector Th cells. Blood. 2012;119:4430–4440. doi: 10.1182/blood-2011-11-392324 22438251

51. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977–986. 8366922

52. Kuhtreiber WM, Washer SL, Hsu E, Zhao M, Reinhold P, Burger D, et al. Low levels of C-peptide have clinical significance for established Type 1 diabetes. Diabet Med. 2015;32:1346–1353. doi: 10.1111/dme.12850 26172028

53. Ito S, Bollard CM, Carlsten M, Melenhorst JJ, Biancotto A, Wang E, et al. Ultra-low dose interleukin-2 promotes immune-modulating function of regulatory T cells and natural killer cells in healthy volunteers. Mol Ther. 2014;22:1388–1395. doi: 10.1038/mt.2014.50 24686272

54. Electronic Medicines Compendium. Proleukin. 2015 Jan 20 [cited 17 Mar 2016]. Available: http://www.medicines.org.uk/emc/medicine/19322.

55. Itano AA, Sims MJ, Siu G. Mechanistic medicine: novel strategies for clinical trials. Autoimmunity. 2010;43:560–571. doi: 10.3109/08916931003674782 20429849

56. Truman LA, Pekalski ML, Kareclas P, Evangelou M, Walker NM, Howlett J, et al. Protocol of the adaptive study of IL-2 dose frequency on regulatory T cells in type 1 diabetes (DILfrequency): a mechanistic, non-randomised, repeat dose, open-label, response-adaptive study. BMJ Open. 2015;5:e009799. doi: 10.1136/bmjopen-2015-009799 26646829

57. Bielekova B, Catalfamo M, Reichert-Scrivner S, Packer A, Cerna M, Waldmann TA, et al. Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci U S A. 2006;103:5941–5946. doi: 10.1073/pnas.0601335103 16585503

58. Herold KC, Gitelman SE, Ehlers MR, Gottlieb PA, Greenbaum CJ, Hagopian W, et al. Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders. Diabetes. 2013;62:3766–3774. doi: 10.2337/db13-0345 23835333

59. Waldron-Lynch F, Henegariu O, Deng S, Preston-Hurlburt P, Tooley J, Flavell R, et al. Teplizumab induces human gut-tropic regulatory cells in humanized mice and patients. Sci Transl Med. 2012;4:118ra12. doi: 10.1126/scitranslmed.3003401 22277969

60. Chatenoud L, Primo J, Bach JF. CD3 antibody-induced dominant self tolerance in overtly diabetic NOD mice. J Immunol. 1997;158:2947–2954. 9058834

61. Herold KC, Burton JB, Francois F, Poumian-Ruiz E, Glandt M, Bluestone JA. Activation of human T cells by FcR nonbinding anti-CD3 mAb, hOKT3gamma1(Ala-Ala). J Clin Invest. 2003;111:409–418. doi: 10.1172/JCI16090 12569167

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