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Diagnostic Value of Interleukin 21 and Carcinoembryonic Antigen Levels in Malignant Pleural Effusions

  • Bunjhoo, Hansvin (Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Ministry of Health of China, Tongji Medical College, Huazhong University of Science and Technology) ;
  • Wang, Zheng-Yun (Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Ministry of Health of China, Tongji Medical College, Huazhong University of Science and Technology) ;
  • Chen, Hui-Long (Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Ministry of Health of China, Tongji Medical College, Huazhong University of Science and Technology) ;
  • Cheng, Sheng (Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Ministry of Health of China, Tongji Medical College, Huazhong University of Science and Technology) ;
  • Xiong, Wei-Ning (Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Ministry of Health of China, Tongji Medical College, Huazhong University of Science and Technology) ;
  • Xu, Yong-Jian (Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Ministry of Health of China, Tongji Medical College, Huazhong University of Science and Technology) ;
  • Cao, Yong (Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Ministry of Health of China, Tongji Medical College, Huazhong University of Science and Technology)
  • Published : 2012.07.31

Abstract

The aim of this study was to evaluate the diagnostic value of interleukin 21(IL-21) and carcinoembryonic antigen (CEA) in tuberculous pleural effusions (TPEs) and malignant pleural effusions (MPEs). Pleural effusion samples from 103 patients were classified on the basis of diagnosis as TPE (n=51) and MPE (n=52). The concentration of IL-21 was determined by ELISA. Lactate dehydrogenase (LDH), adenosine dehydrogenase (ADA) and CEA levels were also determined in all patients. A significant difference was observed in the levels of ADA and CEA (P<0.01), but not in the levels of LDH (P>0.05) between TPE and MPE. The concentration of IL-21 in MPE was significantly higher compared to TPE (P<0.01). With a threshold value of 4.32 pg/ml, IL-21 had a sensitivity of 76.9% (40/52) and a specificity of 80.4% (41/51). Combined detection of IL-21 and CEA had a sensitivity of 69.2% (36/52) and a specificity of 92.2% (47/51). These two markers can contribute to the differential diagnosis of MPEs.

Keywords

References

  1. Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F (2007). Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol, 8, 942-9.
  2. Asao H, Okuyama C, Kumaki S, et al (2001). Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex. J Immunol, 167, 1-5. https://doi.org/10.4049/jimmunol.167.1.1
  3. Baumann MH, Nolan R, Petrini M, et al (2007). Pleural tuberculosis in the United States: incidence and drug resistance. Chest, 131, 1125-32. https://doi.org/10.1378/chest.06-2352
  4. Boucher D, Cournoyer D, Stanners CP, Fuks A (1989). Studies on the control of gene expression of the carcinoembryonic antigen family in human tissue. Cancer Res, 49, 847-52.
  5. Brady J, Hayakawa Y, Smyth MJ, Nutt SL (2004). IL-21 induces the functional maturation of murine NK cells. J Immunol, 172, 2048-58. https://doi.org/10.4049/jimmunol.172.4.2048
  6. Brandt K, Singh PB, Bulfone-Paus S, Ruckert R (2007). Interleukin-21: a new modulator of immunity, infection, and cancer. Cytokine Growth Factor Rev, 18, 223-32. https://doi.org/10.1016/j.cytogfr.2007.04.003
  7. Casal RF, Eapen GA, Morice RC, Jimenez CA (2009). Medical thoracoscopy. Curr Opin Pulmon Med, 15, 313-20. https://doi.org/10.1097/MCP.0b013e32832b8b2d
  8. Chen Z, O'Shea JJ (2008). Th-17 cells: a new fate for differentiating helper T cells. Immunol Res, 41, 87-102. https://doi.org/10.1007/s12026-007-8014-9
  9. Coquet JM, Kyparissoudis K, Pellicci DG, et al (2007). IL-21 is produced by NKT cells and modulates NKT-cell activation and cytokine production. J Immunol, 178, 2827-34. https://doi.org/10.4049/jimmunol.178.5.2827
  10. Davies HE, Nicholson JE, Rahman NM, et al (2010). Outcome of patients with nonspecific pleuritis/fibrosis on thoracoscopic pleural biopsies. Eur J Cardiothorac Surg, 38, 472-7. https://doi.org/10.1016/j.ejcts.2010.01.057
  11. Doelken P (2008). Clinical implications of unexpandable lungs due to pleural disease. Am J Med Sci, 335, 21-5. https://doi.org/10.1097/MAJ.0b013e31815f1a44
  12. Daha NA, Kurreeman FA, Marques RB, et al (2009). Confirmation of STAT4, IL2/IL-21, CTLA4 polymorphism in Rheumatoid Arthritis. Arthritis Rheum, 60, 1255-60. https://doi.org/10.1002/art.24503
  13. Elsaesser H, Sauer K, Brooks DG (2009). IL-21 is required to control chronic viral infections. Science, 324, 1569-72. https://doi.org/10.1126/science.1174182
  14. Ferrer J, Villarino MA, Encabo G, et al (1999). Diagnostic utility of CYFRA 21-1, carcinoembryonic antigen, CA 125 neuron specific enolase, and squamous cell antigen level determinations in the serum and pleural fluid of patients with pleural effusions. Cancer, 86, 1488-95. https://doi.org/10.1002/(SICI)1097-0142(19991015)86:8<1488::AID-CNCR15>3.0.CO;2-Y
  15. Furukawa J, Hara I, Nagai H, et al (2006). Interleukin-21 gene transfection into mouse bladder cancer cells results in tumor rejection through the cytotoxic T lymphocyte response. J Urol, 176, 1198-203. https://doi.org/10.1016/j.juro.2006.04.037
  16. Gupta Bk, Bharat V, Bandyopadhyay D (2010). Role of adenosine desaminase estimation in differentiation of tuberculous from non tuberculous exudative pleural effusions. J Clin Med Res, 2, 79-84.
  17. Habib T, Senadheera S, Weinberg K, KaushanskyK (2002). The common gamma chain (${\gamma}c$) is a required signaling component of the IL-21 receptor and supports IL-21-induced cell proliferation via JAK3. Biochemistry, 41, 8725-31. https://doi.org/10.1021/bi0202023
  18. Hackbarth JS, Murata K, Reilly WM, Algeciras-Schimnich A (2010). Performance of CEA and CA19-9 in identifying pleural effusions caused by malignancies. Clin Biochem, 43, 1051-5. https://doi.org/10.1016/j.clinbiochem.2010.05.016
  19. Harada M, Magara-Koyanagi K, Watarai H, et al (2006). IL -21 induced Be cell apoptosis mediated by natural killer T cells suppress IgE responses. J Exp Med, 203, 2929-37. https://doi.org/10.1084/jem.20062206
  20. Heffner JE (2008). Diagnosis and management of malignant pleural effusions. Respirology, 13, 5-20.
  21. Hoeve MA, Savage ND, de Boer T, et al (2006). Divergent effects of IL-12 and IL-23 on the production of IL-17 by human T cells. Eur J Immunol, 36, 661-70. https://doi.org/10.1002/eji.200535239
  22. Khaleeq G, Musani AI (2008). Emerging paradigms in the management of malignant pleural effusions. Respir Med, 102, 939-48. https://doi.org/10.1016/j.rmed.2008.01.022
  23. Korn T, Bettelli E, Gao W, et al (2007). IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature, 448, 484-7. https://doi.org/10.1038/nature05970
  24. Lim J, Derrick SC, Kolibab K, et al (2009). Early pulmonary cytokine and chemokine responses in mice immunized with three different vaccines against Mycobacterium tuberculosis determined by PCR array. Clin Vaccine Immunol, 16, 122-6. https://doi.org/10.1128/CVI.00359-08
  25. Liu Y, Helms C, Liao W, et al (2008). A genome-wide association study of Psoriasis and psoriatic arthritis identifies new gene loci. PLoS Genet, 4, e100004
  26. Liu Z, Yang L, Cui Y, et al (2009). IL-21 enhances NK cell activation and cytolytic activities and induces TH17 cell differentiation in inflammatory bowel diseases. Inflamm Bowel Dis, 15, 1133-44. https://doi.org/10.1002/ibd.20923
  27. Lucivero G, Pierucci G, Bonomo L (1988). Lymphocyte subsets in peripheral blood and pleural fluid. Eur Respir J, 1, 337-40.
  28. Ma HL, Whitters MJ, Konz RF, et al (2003). IL-21 activates both innate and adaptive immunity to generate potent antitumor responses that require perforin but are independent of IFN-$\gamma$. J Immunol, 171, 608-15. https://doi.org/10.4049/jimmunol.171.2.608
  29. Maskell NA, Gleeson FV, Davies RJ (2003). Standard pleural biopsy versus CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial. Lancet, 361, 1326-30. https://doi.org/10.1016/S0140-6736(03)13079-6
  30. Musani AI (2009). Treatment options for malignant pleural effusion. Curr Opin Pulm Med, 15, 380-7. https://doi.org/10.1097/MCP.0b013e32832c6a8a
  31. Nurieva R, Yang XO, Martinez G, et al (2007). Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature, 448, 480-3. https://doi.org/10.1038/nature05969
  32. Ozaki K, Kikly K, Michalovich D, Young PR, Leonard WJ (2000). Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain. Proc Natl Acad Sci USA, 97, 11439-44. https://doi.org/10.1073/pnas.200360997
  33. Parrish-Novak J, Dillon SR, Nelson A, et al (2000). Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature, 408, 57-63. https://doi.org/10.1038/35040504
  34. Pomjanski N, Juergen Grote H, Doganay P, and et al (2005). Immunocytochemical identification of carcinomas of unknown primary in serous effusions. Diagn Cytopathol, 33, 309-15. https://doi.org/10.1002/dc.20393
  35. Radjenovik-Petrovic T, Pejcic T, Nastasijevic-Borovac D, et al (2009). Diagnostic value of CEA in pleural effusions for differential diagnosis of benign and malignant pleural effusions. Med Arh, 63, 141-2.
  36. Sarra M, Monteleone G (2010). Interleukin-21: a new mediator of inflammation in systemic lupus erythematosus. J Biomed Biotechnol, 294, 582.
  37. Sondergaard H, Frederiksen KS, Thygesen P, et al (2007). Interleukin 21 therapy increases the density of tumor infiltrating CD8(+)T cells and inhibits the growth of syngeneic tumors. Cancer Immunol ther, 56, 1417-28. https://doi.org/10.1007/s00262-007-0285-4
  38. Sondergaard H, Skak K (2009). IL-21: roles in immunopathology and cancer therapy. Tissue Antigens, 74, 467-79. https://doi.org/10.1111/j.1399-0039.2009.01382.x
  39. Spector M, Polak JS (2008). Management of malignant pleural effusions. Semin Respir Crit Care Med, 29, 405-13. https://doi.org/10.1055/s-2008-1081283
  40. Spolski R, Leonard WJ (2008). Interleukin-21: basic biology and implications for cancer and autoimmunity. Annu Rev Immunol, 26, 57-79. https://doi.org/10.1146/annurev.immunol.26.021607.090316
  41. Sriram KB, Relan V, Clarke BE, et al (2011). Diagnostic molecular biomarkers for malignant pleural effusions. Future Oncology, 7, 737-52. https://doi.org/10.2217/fon.11.45
  42. Wang G, Tschoi M, Spolski R, et al (2003). In vivo antitumor activity of interleukin 21 mediated by natural killer cells. Cancer Res, 63, 9016-22.
  43. Wang T, Lv M, Qian Q, et al (2011). Increased frequencies of T helper type 17 cells in tuberculous pleural effusion. Tuberculosis (Edinb), 91, 231-7. https://doi.org/10.1016/j.tube.2011.02.002
  44. Westfall DE, Fan X, Marchevsky AM (2010). Evidence-based guidelines to optimize the selection of antibody panels in cytopathology: pleural effusions with malignant epithelioid cells. Diagn Cytopathol, 38, 9-14.
  45. Yang HB, Shi HZ (2008). T lymphocytes in pleural effusion. Chin Med J (Engl), 121, 579-80.
  46. Ye ZJ, Zhou Q, Zhang JC, et al (2011). CD39+ Regulatory T cells suppress generation and differentiation of Th-17 cells in human malignant pleural effusion via a LAP-dependent mechanism. Respir Res, 12, 77. https://doi.org/10.1186/1465-9921-12-77
  47. Zhou L, Ivanov II, Spolski R, et al (2007). IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol, 8, 967-74. https://doi.org/10.1038/ni1488

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