IFN-γ-INDUCED PROTEIN 10 (IP-10) IN RHEUMATOID ARTHRITIS: LITERATURE REVIEW AND THE AUTHORS' OWN DATA

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease characterized by chronic inflammation of joint synovial membrane and progressive destruction of bone and cartilage. Massive synovial infiltration with immune and inflammatory cells, such as macrophages, monocytes, granulocytes, plasma cells and dendritic cells, B lymphocytes, CD4+ and CD8+ T lymphocytes, presented mainly by effector T cells (T_eff), underlies chronic inflammation and joint destruction in RA. C-X-C-chemokine 10 (CXCL10) was originally identified as a chemokine secreted by several types of cells: macrophages, endothelial cells, and fibroblasts in response to the production of interferon-γ (IFN-γ). It is also known as IFN-γ- induced protein 10 (IP-10). It has been recently discovered that the level of CXCL10 is elevated in the serum and joint tissues of laboratory animals with collagen-induced arthritis. Patients with RA demonstrated higher serum, synovial fluid, and synovial tissue levels of IP-10 than those with osteoarthritis or healthy donors at both early and late stages of the disease. Peripheral blood IP-10, unlike acute-phase measures or indices of activity, may more accurately reflect remission status, which should be kept in mind while deciding for therapy optimization. IP-10 may be a marker for more severe disease and can be used to assess the risk of psoriatic arthritis in patients with psoriasis; its prognostic value in patients with probable RA requires further clarification. Elevated IP-10 levels may be associated with the development of interstitial lung disease in patients with RA and identified in asymptomatic early-stage patients. Thus, IP-10 may be a useful and promising prognostic marker in RA, the significance of which requires further investigation.

1. Насонов ЕЛ, Каратеев ДЕ, Балабанова РМ. Ревматоидный артрит. В кн.: Насонов ЕЛ, Насонова ВА, редакторы. Ревматология: Национальное руководство. Москва: ГЭОТАР-Медиа; 2008. С. 290-331 [Nasonov EL, Karateev DE, Balabanova RM. Rheumatoid arthritis. In: Nasonov EL, Nasonova VA, editors. Revmatologiya: Natsional'noe rukovodstvo [Rheumatology: National guidelance]. Moscow: GEOTAR-Media; 2008. P. 290-331].

2. Firestein G. Evolving concepts of rheumatoid arthritis. Nature. 2003;423:356-61. doi: 10.1038/nature01661

3. Choy E, Panayi G. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med. 2001;344:907-16.

4. doi: 10.1056/NEJM200103223441207

5. Weyand C, Goronzy J. Ectopic germinal center formation in rheumatoid synovitis. Ann NY Acad Sci. 2003;987:140-9. doi: 10.1111/j.1749-6632.2003.tb06042.x

6. Lee EY, Lee ZH, Song YW. CXCL10 and autoimmune diseases. Autoimmun Rev. 2009;8(5):379-83.

7. doi: 10.1016/j.autrev.2008.12.002

8. Schulthess FT, Paroni F, Sauter NS, et al. CXCL10 impairs beta cell function and viability in diabetes through TLR4 signaling. Cell Metab. 2009;9(2):125-39. doi: 10.1016/j.cmet.2009.01.003

9. Rotondi M, Chiovato L, Romagnani S, et al. Role of chemokines in endocrine autoimmune diseases. Endocr Rev. 2007;28(5):492-520. doi: 10.1210/er.2006-0044

10. Soejima K, Rollins BJ. A functional IFN--inducible protein-10/CXCL10-specific receptor expressed by epithelial and endothelial cells that is neither CXCR3 nor glycosaminoglycan. J Immunol. 2001;167:6576-82. doi: 10.4049/jimmunol.167.11.6576

11. Campanella GS, Lee EM, Sun J, Luster AD. CXCR3 and heparin binding sites of the chemokine IP-10 (CXCL10). J Biol Chem. 2003;278:17066-74. doi: 10.1074/jbc.M212077200

12. Campanella GS, Colvin RA, Luster AD. CXCL10 can inhibit endothelial cell proliferation independently of CXCR3. PLoS One. 2010;5:e12700. doi: 10.1371/journal.pone.0012700

13. Shimada A, Morimoto J, Kodama K, et al. Elevated serum IP-10 levels observed in type 1 diabetes. Diabetes Care. 2001;24:510-5. doi: 10.2337/diacare.24.3.510

14. Nicoletti F, Conget I, DiMauro M, et al. Serum concentrations of the interferon-gamma-inducible chemokine IP-10/CXCL10 are augmented in both newly diagnosed type I diabetes mellitus patients and subjects at risk of developing the disease. Diabetologia. 2002;45:1107-10. doi: 10.1007/s00125-002-0879-5

15. Nakagawa Y, Shimada A, Oikawa Y, et al. Two cases of «fulminant» type 1 diabetes suggesting involvement of autoimmunity. Ann N Y Acad Sci. 2003;1005:359-61. doi: 10.1196/annals.1288.059

16. Gabbay MA, Sato MN, Duarte AJ, Dib SA. Serum titres of anti-glutamic acid decarboxylase-65 and anti-IA-2 autoantibodies are associated with different immunoregulatory milieu in newly diagnosed type 1 diabetes patients. Clin Exp Immunol. 2012;168:60-7. doi: 10.1111/j.1365-2249.2011.04538.x

17. Kemp EH, Metcalfe RA, Smith KA, et al. Detection and localization of chemokine gene expression in autoimmune thyroid disease. Clin Endocrinol. 2003;59:207-13. doi: 10.1046/j.1365-2265.2003.01824.x

18. Kimura H, Kimura M, Rose NR, Caturegli P. Early chemokine expression induced by interferon-gamma in a murine model of Hashimoto's thyroiditis. Exp Mol Pathol. 2004;77:161-7.

19. doi: 10.1016/j.yexmp.2004.08.004

20. Antonelli A, Rotondi M, Fallahi P, et al. High levels of circulating CXC chemokine ligand 10 are associated with chronic autoimmune thyroiditis and hypothyroidism. J Clin Endocrinol Metab. 2004;89:5496-9. doi: 10.1210/jc.2004-0977

21. Hanaoka R, Kasama T, Muramatsu M, et al. A novel mechanism for the regulation of IFN-gamma inducible protein-10 expression in rheumatoid arthritis. Arthritis Res Ther. 2003;5:R74-81.

22. doi: 10.1186/ar616

23. Prud'homme GJ, Kono DH, Theofilopoulos AN. Quantitative polymerase chain reaction analysis reveals marked overexpression of interleukin-1 beta, interleukin-10 and interferon gamma mRNA in the lymph nodes of lupus-prone mice. Mol Immunol. 1995;32:495-503. doi: 10.1016/0161-5890(95)00024-9

24. Flier J, Boorsma DM, van Beek PJ, et al. Differential expression of CXCR3 targeting chemokines CXCL10, CXCL9, and CXCL11 in different types of skin inflammation. J Pathol. 2001;194:398-405. doi: 10.1002/1096-9896(200108)194:43.0.CO;2-S

25. Wenzel J, Wö renkä mper E, Freutel S, et al. Enhanced type I interferon signalling promotes Th1-biased inflammation in cutaneous lupus erythematosus. J Pathol. 2005;205:435-42.

26. doi: 10.1002/path.1721

27. Meller S, Winterberg F, Gilliet M, et al. Ultraviolet radiation-induced injury, chemokines, and leukocyte recruitment: an amplification cycle triggering cutaneous lupus erythematosus. Arthritis Rheum. 2005;52:1504-16. doi: 10.1002/art.21034

28. Gambichler T, Genc Z, Skrygan M, et al. Cytokine and chemokine ligand expression in cutaneous lupus erythematosus. Eur J Dermatol. 2012;22:319-23.

29. Narumi S, Takeuchi T, Kobayashi Y, Konishi K. Serum levels of IFN-inducible protein-10 relating to the activity of systemic lupus erythematosus. Cytokine. 2000;12:1561-5.

30. doi: 10.1006/cyto.2000.0757

31. Fujii H, Shimada Y, Hasegawa M, et al. Serum levels of a Th1 chemoattractant IP-10 and Th2 chemoattractants, TARC and MDC, are elevated in patients with systemic sclerosis. J Dermatol Sci. 2004;35:43-51. doi: 10.1016/j.jdermsci.2004.03.001

32. Giuggioli D, Manfredi A, Colaci M, et al. Systemic sclerosis and cryoglobulinemia: our experiencewith overlapping syndrome of scleroderma and severe cryoglobulinemic vasculitis and review of the literature. Autoimmun Rev. 2013;12:1058-63. doi: 10.1016/j.autrev.2013.06.013

33. Ferri C, Zignego AL. Relation between infection and autoimmunity in mixed cryoglobulinemia. Curr Opin Rheumatol. 2000;12:53-60. doi: 10.1097/00002281-200001000-00009

34. Zignego AL, Ferri C, Giannelli F, et al. Prevalence of bcl-2 rearrangement in patients with hepatitis C virus-related mixed cryoglobulinemia with or without B-cell lymphomas. Ann Intern Med. 2002;137:571-80. doi: 10.7326/0003-4819-137-7-200210010-00008

35. Ferri C, Pileri S, Zignego AL. Hepatitis C virus infection and in non-Hodgkin's lymphoma. In: Goedert J, editor. Infectious causes of cancer. Targets for intervention. Totowa, New Jersey: The Human Press Inc.; 2000. P. 349-68.

36. Wedderburn LR, Robinson N, Patel A, et al. Selective recruitment of polarized T cells expressing CCR5 and CXCR3 to the inflamed joints of children with juvenile idiopathic arthritis. Arthritis Rheum. 2000;43:765-74. doi: 10.1002/1529-0131(200004)43:43.0.CO;2-B

37. Ruth JH, Rottman JB, Katschke Jr KJ, et al. Selective lymphocyte chemokine receptor expression in the rheumatoid joint. Arthritis Rheum. 2001;44:2750-60. doi: 10.1002/1529-0131(200112)44:123.0.CO;2-C

38. Kwak HB, Ha H, Kim HN, et al. Reciprocal cross-talk between RANKL and interferon-gamma-inducible protein 10 is responsible for bone-erosive experimental arthritis. Arthritis Rheum. 2008;58:1332-42. doi: 10.1002/art.23372

39. Patel DD, Zachariah JP, Whichard LP. CXCR3 and CCR5 ligands in rheumatoid arthritis synovium. Clin Immunol. 2001;98(1):39-45. doi: 10.1006/clim.2000.4957

40. Hueber W, Tomooka BH, Zhao XY, et al. Proteomic analysis of secreted proteins in early rheumatoid arthritis: anti-citrulline autoreactivity is associated with up regulation of proinflammatory cytokines. Ann Rheum Dis. 2007;66(6):712-9.

41. doi: 10.1136/ard.2006.054924

42. Kokkonen H, Soderstrom I, Rocklov J, et al. Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis. Arthritis Rheum. 2010;62(2):383-91.

43. doi: 10.1002/art.27186

44. Eriksson C, Rantapaa-Dahlqvist S, Sundqvist KG. Changes in chemokines and their receptors in blood during treatment with the TNF inhibitor infliximab in patients with rheumatoid arthritis. Scand J Rheumatol. 2013;42(4):260-5.

45. doi: 10.3109/03009742.2012.754937

46. Pandya J, Lundell A, Andersson K, et al. Blood chemokine profile in untreated early rheumatoid arthritis: CXCL10 as a disease activity marker. Arthritis Res Ther. 2017;19:20.

47. doi: 10.1186/s13075-017-1224-1

48. Ichikawa T, Kageyama Y, Kobayashi H, et al. Etanercept treatment reduces the serum levels of interleukin-15 and interferon-gamma inducible protein-10 in patients with rheumatoid arthritis. Rheumatol Int. 2010;30(6):725-30. doi: 10.1007/s00296-009-1356-y

49. Kuan WP, Tam LS, Wong CK, et al. CXCL 9 and CXCL 10 as sensitive markers of disease activity in patients with rheumatoid arthritis. J Rheumatol. 2010;37(2):257-64.

50. doi: 10.3899/jrheum.090769

51. Van Hooij A, Boeters D, Tjon Kon Fat E, et al. Longitudinal IP-10 serum levels are associated with the course of disease activity and remission in rheumatoid arthritis. Clin Vaccine Immunol. 2017;24(8):e00060-17. doi: 10.1128/CVI.00060-17

52. Yellin M, Paliienko I, Balanescu A, et al. A phase II, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of mdx-1100, a fully human anti-cxcl10 monoclonal antibody, in combination with methotrexate in patients with rheumatoid arthritis. Arthritis Rheum. 2012;64(6):1730-9.

53. doi: 10.1002/art.34330

54. Heller EA, Liu E, Tager AM, et al. Chemokine CXCL10 promotes atherogenesis by modulating the local balance of effector and regulatory T cells. Circulation. 2006;113:2301-12. doi: 10.1161/CIR-CULATIONAHA.105.605121

55. Boyle D, Wei N, Singhal A. The Jak inihibitor Tofacitinib suppresses synovial Jak-stat signalling in rheumatoid arthritis. Arthritis Rheum. 2013;65 Suppl:764.

56. Han BK, Kuzin I, Gaughan JP, et al. Baseline CXCL10 and CXCL13 levels are predictive biomarkers for tumor necrosis factor inhibitor therapy in patients with moderate to severe rheumatoid arthritis: a pilot, prospective study. Arthritis Res Ther. 2015;18:93. doi: 10.1186/s13075-016-0995-0

57. Lee J, Kim B, Jong Jin W, et al. Pathogenic roles of CXCL10 signaling through CXCR3 and TLR4 in macrophages and T cells: relevance for arthritis. Arthritis Res Ther. 2017;19:163.

58. doi: 10.1186/s13075-017-1353-6

59. Turesson C, O'Fallon WM, Crowson CS, et al. Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years. Ann Rheum Dis. 2003;62:722-7.

60. doi: 10.1136/ard.62.8.722

61. Minaur NJ, Jacoby RK, Cosh JA, et al. Outcome after 40 years with rheumatoid arthritis: a prospective study of function, disease activity, and mortality. J Rheumatol. 2004;69 Suppl:3-8.

62. Olson AL, Swigris JJ, Sprunger DB, et al. Rheumatoid arthritis – interstitial lung disease-associated mortality. Am J Resp Crit Care Med. 2011;183:372-8. doi: 10.1164/rccm.201004-0622OC

63. Brown KK. Rheumatoid lung disease. Proc Am Thorac Soc. 2007;4:443-8. doi: 10.1513/pats.200703-045MS

64. Bongartz T, Nannini C, Medina-Velasquez YF, et al. Incidence and mortality of interstitial lung disease in rheumatoid arithritis: a population-based study. Arthritis Rheum. 2010;62:1583-91. doi: 10.1002/art.27405

65. Dawson JK, Fewins HE, Desmond J, et al. Fibrosing alveolitis in patients with rheumatoid arthritis as assessed by high resolution computed tomography, chest radiography, and pulmonary function tests. Thorax. 2001;56:622-7. doi: 10.1136/thorax.56.8.622

66. Doyle TJ, Hunninghake GM, Rosas IO. Subclinical interstitial lung disease: why you should care. Am J Resp Crit Care Med. 2012;185:1147-53. doi: 10.1164/rccm.201108-1420PP

67. Gochuico BR, Avila NA, Chow CK, et al. Progressive preclinical interstitial lung disease in rheumatoid arthritis. Arch Intern Med. 2008;168:159-66. doi: 10.1001/archinternmed.2007.59

68. Dawson JK, Fewins HE, Desmond J, et al. Predictors of progression of HRCT diagnosed fibrosing alveolitis in patients with rheumatoid arthritis. Ann Rheum Dis. 2002;61:517-21.

69. doi: 10.1136/ard.61.6.517

70. Richards TJ, Eggebeen A, Gibson K, et al. Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease. Arthritis Rheum. 2009;60:2183-92. doi: 10.1002/art.24631

71. Shimizu S, Yoshinouchi T, Niimi T, et al. Differing distributions of CXCR3- and CCR4-positive cells among types of interstitial pneumonia associated with collagen vascular diseases. Virchows Arch. 2007;450:51-8. doi: 10.1007/s00428-006-0330-2

72. Chen J, Doyle T, Liu Y, et al. Biomarkers of rheumatoid arthritis-associated interstitial lung disease. Arthritis Rheum. 2015;67(1):28-38. doi: 10.1002/art.38904

73. Abji F, Remy A, Pollock R, et al. CXCL10 is a possible biomarker for the development of psoriatic arthritis among patients with psoriasis. Arthritis Rheuma. 2016;68:2911-6. doi: 10.1002/art.39800

74. Авдеева АС, Новиков АА, Александрова ЕН и др. Значение показателей цитокинового профиля при оценке эффективности терапии моноклональными антителами

75. к рецепторам интерлейкина-6 при ревматоидном артрите. Клиническая медицина. 2014;(1):28-34 [Avdeeva AS,

76. Novikov AA, Aleksandrova EN, et al. The value of cytokine profile in evaluating the effectiveness of monoclonal antibodies to interleukin-6 receptors in rheumatoid arthritis. Klinicheskaya Meditsina. 2014;(1):28-34 (In Russ.)].

77. Авдеева АС, Александрова ЕН, Новиков АА и др. Сравнение влияния терапии ритуксимабом и тоцилизумабом на активность и лабораторные показатели у больных ревматоидным артритом. Клиническая фармакология

78. и терапия. 2014;(1):25-32 [Avdeeva AS, Aleksandrova EN, Novikov AA, et al. Comparison of the effect of rituximab and tocilizumab on activity and laboratory parameters in patients with rheumatoid arthritis. Klinicheskaya Farmakologiya i Terapiya. 2014;(1):25-32 (In Russ.)].

79. Авдеева АС, Новиков АА, Александрова ЕН и др. Динамика уровней цитокинов на фоне терапии метотрексатом и адалимумабом у пациентов с ранним ревматоидным артритом (исследование РЕМАРКА). Научно-практическая ревматология. 2014;52(3):254-63 [Avdeeva AS, Novikov AA, Aleksandrova EN, et al. Changes of cytokine levels during therapy with methotrexate and adalimumab in patients with early rheumatoid arthritis (REMARCA study). Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2014;52(3):254-63 (In Russ.)]. doi: 10.14412/1995-4484-2014-254-262

80. Авдеева АС, Новиков АА, Александрова ЕН и др. Взаимосвязь показателей цитокинового профиля с активностью заболевания и уровнем аутоантител при раннем ревматоидном артрите (РА). Клиническая лабораторная диагностика. 2014;59(9):37 [Avdeeva AS, Novikov AA, Aleksandrova EN, et al. Interrelation of cytokine profile with disease activity and level of autoantibodies in early rheumatoid arthritis (RA). Klinicheskaya Laboratornaya Diagnostika. 2014;59(9):37 (In Russ.)].