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Clinical implications of elevated serum interleukin-6 in IgG4-related disease


Autoři: Satoshi Tsukuda aff001;  Tsukasa Ikeura aff001;  Takashi Ito aff001;  Koh Nakamaru aff001;  Masataka Masuda aff001;  Yuichi Hori aff001;  Manami Ikemune aff001;  Masato Yanagawa aff001;  Toshihiro Tanaka aff001;  Takashi Tomiyama aff001;  Takashi Yamaguchi aff001;  Yugo Ando aff001;  Kazushige Uchida aff002;  Toshiro Fukui aff001;  Akiyoshi Nishio aff001;  Rika Terasawa aff003;  Noboru Tanigawa aff003;  Kazuichi Okazaki aff001
Působiště autorů: Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Hirakata, Osaka, Japan aff001;  Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan aff002;  Department of Radiology, Kansai Medical University, Hirakata, Osaka, Japan aff003
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227479

Souhrn

Introduction

Some patients with IgG4-related disease (IgG4-RD) exhibit elevated serum interleukin (IL)-6 with excessive inflammatory reactions or with repeating relapse. To date few reports pertaining to clinical implications of elevated serum IL-6 in IgG4-RD patients have been published. The aims of the current retrospective study were to investigate the clinical implications of elevated serum IL-6 in IgG4-RD patients, and to examine whether IL-6 can predict the activity and/or relapse of the disease.

Materials and methods

We examined the clinical picture at the onset of 43 patients who were diagnosed with IgG4-RD in our hospital and were able to measure serum IL-6 before steroid treatment.

Results

The median level of serum IL-6 was 2.2 pg/mL. There was a significant correlation between IL-6 and C-reactive protein (CRP) level (r = 0.397, p = 0.008), hemoglobin level (r = -0.390, p = 0.010) and albumin level (r = -0.556, p < 0.001). When 43 patients were divided into two groups by using a cut-off IL-6 of 4 pg/mL, the high IL-6 group showed higher age, lower albumin, higher CRP and higher aspartate aminotransferase (AST) (age p = 0.014, albumin p = 0.006, CRP p <0.001, AST p = 0.009). Hepatic swelling and splenomegaly were significantly more prevalent in the high IL-6 group than it was in the low IL-6 group (liver p < 0.001, spleen p = 0.020). Biliary tract involvement tended to admit more in the high IL-6 group (p = 0.060).

Conclusion

Serum IL-6 level at the onset of IgG4-RD may be significantly correlated with clinical inflammatory parameters and it may also be associated with involvement of the bile duct, liver, and spleen.

Klíčová slova:

Albumins – Diagnostic medicine – Hemoglobin – Kidneys – Pancreas – Spleen – Steroid therapy – Splenomegaly


Zdroje

1. Okazaki K, Uchida K, Ikeura T, Takaoka M. Current concept and diagnosis of IgG4-related disease in the hepato-bilio-pancreatic system. J Gastroenterol. 2013;48(3):303–14. Epub 2013/02/19. doi: 10.1007/s00535-012-0744-3 23417598; PubMed Central PMCID: PMC3698437.

2. Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012;22(1):21–30. Epub 2012/01/06. doi: 10.1007/s10165-011-0571-z 22218969.

3. Hart PA, Kamisawa T, Brugge WR, Chung JB, Culver EL, Czako L, et al. Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis. Gut. 2013;62(12):1771–6. Epub 2012/12/13. doi: 10.1136/gutjnl-2012-303617 23232048; PubMed Central PMCID: PMC3862979.

4. Sah RP, Chari ST, Pannala R, Sugumar A, Clain JE, Levy MJ, et al. Differences in clinical profile and relapse rate of type 1 versus type 2 autoimmune pancreatitis. Gastroenterology. 2010;139(1):140–8; quiz e12-3. Epub 2010/04/01. doi: 10.1053/j.gastro.2010.03.054 20353791.

5. Stimac D, Fisic E, Milic S, Bilic-Zulle L, Peric R. Prognostic values of IL-6, IL-8, and IL-10 in acute pancreatitis. J Clin Gastroenterol. 2006;40(3):209–12. Epub 2006/04/25. doi: 10.1097/00004836-200603000-00007 16633121.

6. Nara M, Komatsuda A, Omokawa A, Togashi M, Okuyama S, Sawada K, et al. Serum interleukin 6 levels as a useful prognostic predictor of clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease. Mod Rheumatol. 2014;24(4):633–6. Epub 2013/11/21. doi: 10.3109/14397595.2013.844390 24252021.

7. Yamamoto M, Takahashi H, Hasebe K, Suzuki C, Naishiro Y, Hayashi T, et al. The analysis of interleukin-6 in patients with systemic IgG4-related plasmacytic syndrome—expansion of SIPS to the territory of Castleman's disease. Rheumatology (Oxford). 2009;48(7):860–2. Epub 2009/05/19. doi: 10.1093/rheumatology/kep098 19447768.

8. Ikeura T, Horitani S, Masuda M, Kasai T, Yanagawa M, Miyoshi H, et al. IgG4-related Disease Involving Multiple Organs with Elevated Serum Interleukin-6 Levels. Intern Med. 2016;55(18):2623–8. Epub 2016/09/16. doi: 10.2169/internalmedicine.55.6919 27629957.

9. Committee of the Japan Diabetes Society on the Diagnostic Criteria of Diabetes M, Seino Y, Nanjo K, Tajima N, Kadowaki T, Kashiwagi A, et al. Report of the committee on the classification and diagnostic criteria of diabetes mellitus. J Diabetes Investig. 2010;1(5):212–28. Epub 2010/10/19. doi: 10.1111/j.2040-1124.2010.00074.x 24843435; PubMed Central PMCID: PMC4020724.

10. Matsushita M, Yamashina M, Ikeura T, Shimatani M, Uchida K, Takaoka M, et al. Effective steroid pulse therapy for the biliary stenosis caused by autoimmune pancreatitis. Am J Gastroenterol. 2007;102(1):220–1. Epub 2007/02/06. 17278279.

11. Tomiyama T, Uchida K, Matsushita M, Ikeura T, Fukui T, Takaoka M, et al. Comparison of steroid pulse therapy and conventional oral steroid therapy as initial treatment for autoimmune pancreatitis. J Gastroenterol. 2011;46(5):696–704. Epub 2010/12/29. doi: 10.1007/s00535-010-0361-y 21188426.

12. Masamune A, Nishimori I, Kikuta K, Tsuji I, Mizuno N, Iiyama T, et al. Randomised controlled trial of long-term maintenance corticosteroid therapy in patients with autoimmune pancreatitis. Gut. 2017;66(3):487–94. Epub 2016/08/21. doi: 10.1136/gutjnl-2016-312049 27543430.

13. Takahashi W, Nakada TA, Yazaki M, Oda S. Interleukin-6 Levels Act as a Diagnostic Marker for Infection and a Prognostic Marker in Patients with Organ Dysfunction in Intensive Care Units. Shock. 2016;46(3):254–60. Epub 2016/05/14. doi: 10.1097/SHK.0000000000000616 27172160.

14. Frulloni L, Scattolini C, Falconi M, Zamboni G, Capelli P, Manfredi R, et al. Autoimmune pancreatitis: differences between the focal and diffuse forms in 87 patients. Am J Gastroenterol. 2009;104(9):2288–94. Epub 2009/07/02. doi: 10.1038/ajg.2009.327 19568232.

15. Wallace ZS, Mattoo H, Mahajan VS, Kulikova M, Lu L, Deshpande V, et al. Predictors of disease relapse in IgG4-related disease following rituximab. Rheumatology (Oxford). 2016;55(6):1000–8. Epub 2016/02/19. doi: 10.1093/rheumatology/kev438 26888853; PubMed Central PMCID: PMC4900135.

16. Nishimoto N, Sasai M, Shima Y, Nakagawa M, Matsumoto T, Shirai T, et al. Improvement in Castleman's disease by humanized anti-interleukin-6 receptor antibody therapy. Blood. 2000;95(1):56–61. Epub 1999/12/23. 10607684.

17. van Rhee F, Fayad L, Voorhees P, Furman R, Lonial S, Borghaei H, et al. Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease. J Clin Oncol. 2010;28(23):3701–8. Epub 2010/07/14. doi: 10.1200/JCO.2009.27.2377 20625121.

18. Zoshima T, Yamada K, Hara S, Mizushima I, Yamagishi M, Harada K, et al. Multicentric Castleman Disease With Tubulointerstitial Nephritis Mimicking IgG4-related Disease: Two Case Reports. Am J Surg Pathol. 2016;40(4):495–501. Epub 2015/11/26. doi: 10.1097/PAS.0000000000000575 26598921.

19. Terasaki Y, Ikushima S, Matsui S, Hebisawa A, Ichimura Y, Izumi S, et al. Comparison of clinical and pathological features of lung lesions of systemic IgG4-related disease and idiopathic multicentric Castleman's disease. Histopathology. 2017;70(7):1114–24. Epub 2017/02/17. doi: 10.1111/his.13186 28207938.

20. Sato Y, Kojima M, Takata K, Morito T, Asaoku H, Takeuchi T, et al. Systemic IgG4-related lymphadenopathy: a clinical and pathologic comparison to multicentric Castleman's disease. Mod Pathol. 2009;22(4):589–99. Epub 2009/03/10. doi: 10.1038/modpathol.2009.17 19270642.

21. Kurose N. Clinicopathological Analysis between IgG4-related and Non-IgG4-related Diseases Occurring in Various Organs and Tissues: Re-evaluation of Comprehensive Diagnostic Criteria and Usefulness of Interleukin-6 Immunostaining. J Kanazawa Med Univ. 2016;41:76–85.

22. Cheuk W, Chan JK. Lymphadenopathy of IgG4-related disease: an underdiagnosed and overdiagnosed entity. Semin Diagn Pathol. 2012;29(4):226–34. Epub 2012/10/17. doi: 10.1053/j.semdp.2012.07.001 23068302.

23. Kawashima H, Utsugi A, Shibamiya A, Iida K, Mimura N, Ohashi H, et al. Consideration concerning similarities and differences between ANCA-associated vasculitis and IgG-4-related diseases: case series and review of literature. Immunologic research. 2019;67(1):99–107. Epub 2019/02/09. doi: 10.1007/s12026-019-9070-7 30734199.

24. Kasashima S, Kawashima A, Kasashima F, Endo M, Matsumoto Y, Kawakami K. Inflammatory features, including symptoms, increased serum interleukin-6, and C-reactive protein, in IgG4-related vascular diseases. Heart Vessels. 2018;33(12):1471–81. Epub 2018/06/23. doi: 10.1007/s00380-018-1203-8 29931542.

25. Liu AY, Nabel CS, Finkelman BS, Ruth JR, Kurzrock R, van Rhee F, et al. Idiopathic multicentric Castleman's disease: a systematic literature review. Lancet Haematol. 2016;3(4):e163–75. Epub 2016/04/12. doi: 10.1016/S2352-3026(16)00006-5 27063975.

26. Otani K, Inoue D, Fujikura K, Komori T, Abe-Suzuki S, Tajiri T, et al. Idiopathic multicentric Castleman's disease: a clinicopathologic study in comparison with IgG4-related disease. Oncotarget. 2018;9(6):6691–706. Epub 2018/02/23. doi: 10.18632/oncotarget.24068 29467920; PubMed Central PMCID: PMC5805506.

27. Umemura T, Zen Y, Hamano H, Joshita S, Ichijo T, Yoshizawa K, et al. Clinical significance of immunoglobulin G4-associated autoimmune hepatitis. J Gastroenterol. 2011;46 Suppl 1:48–55. Epub 2010/09/24. doi: 10.1007/s00535-010-0323-4 20862498.

28. Canivet CM, Anty R, Patouraux S, Saint-Paul MC, Lebeaupin C, Gual P, et al. Immunoglobulin G4-associated autoimmune hepatitis may be found in Western countries. Dig Liver Dis. 2016;48(3):302–8. Epub 2015/11/11. doi: 10.1016/j.dld.2015.10.005 26553036.

29. Nikias GA, Batts KP, Czaja AJ. The nature and prognostic implications of autoimmune hepatitis with an acute presentation. J Hepatol. 1994;21(5):866–71. Epub 1994/11/01. doi: 10.1016/s0168-8278(94)80251-3 7890904.

30. Tilg H, Wilmer A, Vogel W, Herold M, Nolchen B, Judmaier G, et al. Serum levels of cytokines in chronic liver diseases. Gastroenterology. 1992;103(1):264–74. Epub 1992/07/01. doi: 10.1016/0016-5085(92)91122-k 1612333.

31. Ishimaru M, Yusuke N, Tsukimoto M, Harada H, Takenouchi T, Kitani H, et al. Purinergic signaling via P2Y receptors up-mediates IL-6 production by liver macrophages/Kupffer cells. J Toxicol Sci. 2014;39(3):413–23. Epub 2014/05/23. doi: 10.2131/jts.39.413 24849676.

32. Pozo AL, Godfrey EM, Bowles KM. Splenomegaly: investigation, diagnosis and management. Blood Rev. 2009;23(3):105–11. Epub 2008/12/09. doi: 10.1016/j.blre.2008.10.001 19062140.

33. Matsubayashi H, Uesaka K, Kanemoto H, Aramaki T, Nakaya Y, Kakushima N, et al. Reduction of splenic volume by steroid therapy in cases with autoimmune pancreatitis. J Gastroenterol. 2013;48(8):942–50. Epub 2012/10/19. doi: 10.1007/s00535-012-0692-y 23076542.

34. Suematsu S, Matsuda T, Aozasa K, Akira S, Nakano N, Ohno S, et al. IgG1 plasmacytosis in interleukin 6 transgenic mice. Proc Natl Acad Sci U S A. 1989;86(19):7547–51. Epub 1989/10/01. doi: 10.1073/pnas.86.19.7547 2798426; PubMed Central PMCID: PMC298102.

35. Katsume A, Saito H, Yamada Y, Yorozu K, Ueda O, Akamatsu K, et al. Anti-interleukin 6 (IL-6) receptor antibody suppresses Castleman's disease like symptoms emerged in IL-6 transgenic mice. Cytokine. 2002;20(6):304–11. Epub 2003/03/14. doi: 10.1006/cyto.2002.2012 12633573.

36. Sasaki T, Akiyama M, Kaneko Y, Mori T, Yasuoka H, Suzuki K, et al. Distinct features distinguishing IgG4-related disease from multicentric Castleman's disease. RMD open. 2017;3(1):e000432. Epub 2017/09/30. doi: 10.1136/rmdopen-2017-000432 28959455; PubMed Central PMCID: PMC5617886.


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