#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Circulating Th17.1 cells as candidate for the prediction of therapeutic response to abatacept in patients with rheumatoid arthritis: An exploratory research


Autoři: Shinji Maeda aff001;  Satoshi Osaga aff002;  Tomoyo Maeda aff001;  Norihisa Takeda aff001;  Shin-ya Tamechika aff001;  Taio Naniwa aff001;  Akio Niimi aff001
Působiště autorů: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan aff001;  Clinical Research Management Center, Nagoya City University Hospital, Nagoya, Japan aff002
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0215192

Souhrn

T-helper (Th)17.1 cells exhibit high pathogenicity in inflammatory diseases. This study aimed to identify the changes in the proportions of Th subsets, including Th17.1, which are associated with abatacept treatment response in Japanese patients with rheumatoid arthritis. On the basis of the results, we assessed whether Th17.1 is a potential cellular biomarker. Multicolor flow cytometry was used to determine the circulating Th subsets among CD4+ T lymphocytes in 40 patients with rheumatoid arthritis before abatacept treatment. All the patients received abatacept treatment for 24 weeks; changes in disease activity score, including 28-joint count C-reactive protein, and responsiveness indicated by other indices to abatacept treatment were evaluated according the European League Against Rheumatism criteria (good and moderate responders and nonresponders). The correlation between the abatacept responses and the proportions of Th subsets (baseline) was analyzed. Logistic regression analysis with inverse probability weighting method was performed to calculate the odds ratio adjusted for patient characteristics. The proportion of baseline Th17.1 cells was significantly lower in patients categorized as good responders than in those categorized as non-good responders (moderate responders and nonresponders; p = 0.0064). The decrease in 28-joint count C-reactive protein after 24 weeks of abatacept therapy showed a significant negative correlation with the proportion of Th17.1 cells. The adjusted odds ratio for achieving good response in patients with baseline Th17.1 levels below the median value was 14.6 (95% confidence interval, 2.9–72.3; p = 0.0021) relative to that in the remaining patients. The proportion of Th17.1 cells at baseline is a good candidate for predicting abatacept treatment response in Japanese patients. These novel findings may represent a significant step in the pursuit of precision medicine.

Klíčová slova:

Rheumatoid arthritis – Cytokines – Inflammation – T cells – Flow cytometry – Biomarkers – C-reactive proteins – Regulatory T cells


Zdroje

1. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388: 2023–2038. doi: 10.1016/S0140-6736(16)30173-8 27156434

2. Felson DT, Smolen JS, Wells G, Zhang B, Van Tuyl LHD, Funovits J, et al. American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Arthritis Rheum. 2011;63: 573–586. doi: 10.1002/art.30129 21294106

3. Van Tuyl LHD, Vlad SC, Felson DT, Wells G, Boers M. Defining remission in rheumatoid arthritis: results of an initial American College of Rheumatology/European League Against Rheumatism consensus conference. Arthritis Rheum. 2009;61: 704–710. doi: 10.1002/art.24392 19405006

4. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2007;365: 2205–2219. doi: 10.1056/NEJMra1004965 22150039

5. Kremer JM, Westhovens R, Leon M, Di Giorgio E, Alten R, Steinfeld S, et al. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med. 2003;349: 1907–1915. doi: 10.1056/NEJMoa035075 14614165

6. Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, et al. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2006;144: 865–876. doi: 10.7326/0003-4819-144-12-200606200-00003 16785475

7. Maxwell LJ, Singh JA. Abatacept for rheumatoid arthritis: A cochrane systematic review. J Rheumatol. 2010;37: 234–245. doi: 10.3899/jrheum.091066 20080922

8. Hirota K, Hashimoto M, Yoshitomi H, Tanaka S, Nomura T, Yamaguchi T, et al. T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis. J Exp Med. 2007;204: 41–47. doi: 10.1084/jem.20062259 17227914

9. Hirota K, Yoshitomi H, Hashimoto M, Maeda S, Teradaira S, Sugimoto N, et al. Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J Exp Med. 2007;204: 2803–2812. doi: 10.1084/jem.20071397 18025126

10. Bettelli E, Korn T, Oukka M, Kuchroo VK. Induction and effector functions of T(H)17 cells. Nature. 2008;453: 1051–1057. doi: 10.1038/nature07036 18563156

11. Kochi Y, Okada Y, Suzuki A, Ikari K, Terao C, Takahashi A, et al. A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. Nat Genet. 2010;42: 515–519. doi: 10.1038/ng.583 20453841

12. Paulissen SMJ, van Hamburg JP, Dankers W, Lubberts E. The role and modulation of CCR6+ Th17 cell populations in rheumatoid arthritis. Cytokine. 2015;74: 43–53. doi: 10.1016/j.cyto.2015.02.002 25828206

13. Ramesh R, Kozhaya L, McKevitt K, Djuretic IM, Carlson TJ, Quintero MA, et al. Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids. J Exp Med. 2014;211: 89–104. doi: 10.1084/jem.20130301 24395888

14. van Hamburg JP, Tas SW. Molecular mechanisms underpinning T helper 17 cell heterogeneity and functions in rheumatoid arthritis. J Autoimmun. 2018;87: 69–81. doi: 10.1016/j.jaut.2017.12.006 29254845

15. Chikanza IC, Kozaci DL. Corticosteroid resistance in rheumatoid arthritis: molecular and cellular perspectives. Rheumatology. 2004;43: 1337–1345. doi: 10.1093/rheumatology/keh333 15304669

16. Firestein GS, McInnes IB. Immunopathogenesis of rheumatoid arthritis. Immunity. 2017;46: 183–196. doi: 10.1016/j.immuni.2017.02.006 28228278

17. Nakayamada S, Kubo S, Yoshikawa M, Miyazaki Y, Yunoue N, Iwata S, et al. Differential effects of biological DMARDs on peripheral immune cell phenotypes in patients with rheumatoid arthritis. Rheumatology. 2018;57: 164–174. doi: 10.1093/rheumatology/kex012 28371836

18. Ermann J, Rao DA, Teslovich NC, Brenner MB, Raychaudhuri S. Immune cell profiling to guide therapeutic decisions in rheumatic diseases. Nat Rev Rheumatol. 2015;11: 541–551. doi: 10.1038/nrrheum.2015.71 26034835

19. Falconer J. Toward cellular biomarkers for rheumatoid arthritis. Rheumatology (Oxford). 2018; 57: 10–11. doi: 10.1093/rheumatology/kex283 28968814

20. Arnett FC, Edworthy SM, Bloch DA, Mcshane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31: 315–324. doi: 10.1002/art.1780310302 3358796

21. Inoue E, Yamanaka H, Hara M, Tomatsu T, Kamatani N. Comparison of Disease Activity Score (DAS)28-erythrocyte sedimentation rate and DAS28-C-reactive protein threshold values. Ann Rheum Dis. 2007;66: 407–409. doi: 10.1136/ard.2006.054205 16926186

22. Austin PC. The performance of different propensity score methods for estimating marginal hazard ratios. Stat Med. 2013;32: 2837–2849. doi: 10.1002/sim.5705 23239115

23. Joffe MM, Rosenbaum PR. Invited commentary: propensity scores. Am J Epidemiol. 1999;150: 327–333. doi: 10.1093/oxfordjournals.aje.a010011 10453808

24. Nagafuji K, Matsuo K, Teshima T, Mori S, Sakamaki H, Hidaka M, et al. Peripheral blood stem cell versus bone marrow transplantation from HLA-identical sibling donors in patients with leukemia: a propensity score-based comparison from the Japan Society for Hematopoietic Stem Cell Transplantation registry. Int J Hematol. 2010;91: 855–864. doi: 10.1007/s12185-010-0581-1 20464644

25. Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48: 452–458. doi: 10.1038/bmt.2012.244 23208313

26. Lumley T. Analysis of complex survey samples. J Stat Soft. 2004;9: 1–19. doi: 10.18637/jss.v009.i08

27. Wickham H. ggplot2: elegant graphics for data analysis. New York: Springer-Verlag New York; 2009.

28. Maecker HT, McCoy JP, Nussenblatt R. Standardizing immunophenotyping for the Human Immunology Project. Nat Rev Immunol. 2012;12: 191–200. doi: 10.1038/nri3158 22343568

29. Stadhouders R, Lubberts E, Hendriks RW. A cellular and molecular view of T helper 17 cell plasticity in autoimmunity. Journal of Autoimmunity. 2018. pp. 1–15. doi: 10.1016/j.jaut.2017.12.007 29275836

30. Agalioti T, Villablanca EJ, Huber S, Gagliani N. TH17 cell plasticity: The role of dendritic cells and molecular mechanisms. Journal of Autoimmunity. 2018. pp. 50–60. doi: 10.1016/j.jaut.2017.12.003 29371049

31. Revu S, Wu J, Henkel M, Rittenhouse N, Menk A, Delgoffe GM, et al. IL-23 and IL-1β Drive Human Th17 Cell Differentiation and Metabolic Reprogramming in Absence of CD28 Costimulation. Cell Rep. 2018;22: 2642–2653. doi: 10.1016/j.celrep.2018.02.044 29514093

32. Penatti A, Facciotti F, De Matteis R, Larghi P, Paroni M, Murgo A, et al. Differences in serum and synovial CD4+ T cells and cytokine profiles to stratify patients with inflammatory osteoarthritis and rheumatoid arthritis. Arthritis Res Ther. 2017;19: 103. doi: 10.1186/s13075-017-1305-1 28526072

33. Behrens F, Tak PP, Østergaard M, Stoilov R, Wiland P, Huizinga TW, et al. MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial. Ann Rheum Dis. 2015;74: 1058–1064. doi: 10.1136/annrheumdis-2013-204816 24534756

34. Bouguermouh S, Fortin G, Baba N, Rubio M, Sarfati M. CD28 co-stimulation down regulates Th17 development. PLoS One. 2009;4. doi: 10.1371/journal.pone.0005087 19333372

35. Zhang Q, Vignali DAA. Co-stimulatory and Co-inhibitory Pathways in Autoimmunity. Immunity. Elsevier Inc.; 2016;44: 1034–1051. doi: 10.1016/j.immuni.2016.04.017 27192568

36. Ying H, Yang L, Qiao G, Li Z, Zhang L, Yin F, et al. Cutting Edge: CTLA-4–B7 Interaction Suppresses Th17 Cell Differentiation. J Immunol. 2010;185: 1375–1378. doi: 10.4049/jimmunol.0903369 20601598

37. Krummey SM, Cheeseman JA, Conger JA, Jang PS, Mehta AK, Kirk AD, et al. High CTLA-4 expression on Th17 cells results in increased sensitivity to CTLA-4 coinhibition and resistance to belatacept. Am J Transplant. 2014;14: 607–614. doi: 10.1111/ajt.12600 24730049

38. Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, Fehervari Z, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 2008;322: 271–275. doi: 10.1126/science.1160062 18845758

39. Waterhouse P, Penninger JM, Timms E, Wakeham A, Shahinian A, Lee KP, et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science. 1995; 270: 985–988. doi: 10.1126/science.270.5238.985 7481803

40. Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity. 1995;3: 541–547. doi: 10.1016/1074-7613(95)90125-6 7584144

41. Basdeo SA, Cluxton D, Sulaimani J, Moran B, Canavan M, Orr C, et al. Ex-Th17 (nonclassical Th1) cells are functionally distinct from classical Th1 and Th17 cells and are not constrained by regulatory T cells. J Immunol. 2017;198: 2249–2259. doi: 10.4049/jimmunol.1600737 28167631

42. Kubo S, Saito K, Hirata S, Fukuyo S, Yamaoka K, Sawamukai N, et al. Abatacept inhibits radiographic progression in patients with rheumatoid arthritis: a retrospective analysis of 6 months of abatacept treatment in routine clinical practice, The ALTAIR Study. Mod Rheumatol. 2014;24: 42–51. doi: 10.3109/14397595.2013.854051 24261758

43. Harigai M, Ishiguro N, Inokuma S, Mimori T, Ryu J, Takei S, et al. Postmarketing surveillance of the safety and effectiveness of abatacept in Japanese patients with rheumatoid arthritis. Mod. Rheumatol. 2016;26: 491–498. doi: 10.3109/14397595.2015.1123211 26635183

44. Gottenberg JE, Ravaud P, Cantagrel A, Combe B, Flipo RM, Schaeverbeke T, et al. Positivity for anti-cyclic citrullinated peptide is associated with a better response to abatacept: data from the “Orencia and rheumatoid arthritis” registry. Ann Rheum Dis. 2012;71: 1815–1819. doi: 10.1136/annrheumdis-2011-201109 22615458

45. Leffers HC, Ostergaard M, Glintborg B, Krogh NS, Foged H, Tarp U, et al. Efficacy of abatacept and tocilizumab in patients with rheumatoid arthritis treated in clinical practice: results from the nationwide Danish DANBIO registry. Ann Rheum Dis. 2011;70: 1216–1222. doi: 10.1136/ard.2010.140129 21551512

46. Piantoni S, Colombo E, Tincani A, Airò P, Scarsi M. Predictive factors of abatacept therapy discontinuation in patients with rheumatoid arthritis. Clin Rheumatol. 2016;35: 1065–1069. doi: 10.1007/s10067-016-3185-1 26809797

47. Scarsi M, Ziglioli T, Airo’ P. Baseline numbers of circulating CD28-negative T cells may predict clinical response to abatacept in patients with rheumatoid arthritis. J Rheumatol. 2011;38: 2105–2111. doi: 10.3899/jrheum.110386 21807779

48. Scarsi M, Zanotti C, Chiarini M, Imberti L, Piantoni S, Frassi M, et al. Reduction of peripheral blood T cells producing IFN-γ and IL-17 after therapy with abatacept for rheumatoid arthritis. Clin Exp Rheumatol. 2014;32: 204–210. Available: http://europepmc.org/abstract/med/24428959 24428959


Článok vyšiel v časopise

PLOS One


2019 Číslo 11
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#