IgG4 immunoglobulin subclass and related pathological conditions or how to effectively imitate cancer disease

Česká verzia

Authors: Chovancová Zita ¹; Filipenský Petr ²; Rotnáglová Simona ²; Zambo Staniczková Iva ⁴; Shatokhina Tetiana ⁴; Novosádová Klára ⁵; Litzman Jiří ¹
Authors place of work: Ústav klinické imunologie a alergologie LF MU a FN u sv. Anny v Brně ¹; Urologické oddělení LF MU a FN u sv. Anny v Brně ²; Onkologicko-chirurgické oddělení LF MU a FN u sv. Anny v Brně ³; I. ústav patologie LF MU a FN u sv. Anny v Brně ⁴; Klinika zobrazovacích metod LF MU a FN u sv. Anny v Brně ⁵
Published in the journal: Klin Onkol 2022; 35(1): 20-31
Category: Reviews
doi: https://doi.org/10.48095/ ccko202220

Summary

Background: IgG4 is the least represented subclass of human imunnoglobulines G (IgG) in serum and differs from other antibodies by its unique biological properties. Although its function in the immune response is not entirely clear, it is mainly involved in the regulation of the immune response. It is formed as a result of chronic or strong antigenic stimulation; in such a case, it becomes a predominantly formed IgG subclass. IgG4 play a key role in the immune tolerance in allergies and tumors. The tolerogenic potential of IgG4 is used in the treatment of allergic diseases using the allergen immunotherapy; at the same time, it is also involved in inducing the immunological tolerance in the microenvironment of tumors, which promotes tumor progression. The increase of serum IgG4 is associated with relatively recently described groups of diseases. In addition to the IgG4-autoimmune diseases, it is mainly connected with IgG4-associated diseases (IgG4-RD) where various organs of the human body are affected by the formation of fibrous and sclerosing deposits in this group of the immune-mediated diseases, which leads to specific organ dysfunction. The most commonly affected organs include the pancreas and large salivary glands; moreover, the orbits and lacrimal glands, the biliary tract, the lungs, the kidneys, the retroperitoneum, the aorta, the meninges, and the thyroid gland may also be affected. It is not entirely clear whether these patients have a higher prevalence of cancer than the general population; however, there is also another relationship between IgG4 and cancer. IgG4-RD very often imitate advanced cancer in medical imaging techniques, so its existence should also be considered in the differential diagnosis of malignancies. Purpose: The aim of this article is to draw attention of clinical oncologists to the issue of IgG4-associated diseases group which can mimic cancer condition in various organs in the human body. Therefore, it is necessary to bear them in mind in the differential diagnosis of malignant diseases.

Keywords:

malignancy – differential diagnosis – IgG4 – IgG4-related disease – immunoregulation

Zdroje

1. Ballieux RE, Bernier GM, Tominaga K et al. Gamma globulin antigenic types defined by heavy chain determinants. Science 1964; 145 (3628): 168–170. doi: 10.1126/science.145.3628.168.

2. Kamisawa T, Funata N, Hayashi Y et al. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol 2003; 38 (10): 982–984. doi: 10.1007/s00535-003-1175-y.

3. Koneczny I. Update on IgG4-mediated autoimmune diseases: new insights and new family members. Autoimmun Rev 2020; 19 (10): 102646. doi: 10.1016/j.autrev.2020.102646.

4. Jensen-Jarolim E, Bax HJ, Bianchini R et al. AllergoOncology: opposite outcomes of immune tolerance in allergy and cancer. Allergy 2018; 73 (2): 328–340. doi: 10.1111/all.13311.

5. Mikulová Š, Jílek D, Richter J. Nemoc asociovaná s IgG4: úvod, diagnostika, patogeneze; 1. část. Alergie 2015; 17 (1): 16–24.

6. Hamano H, Kawa S, Horiuchi A et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 2001; 344 (10): 732–738. doi: 10.1056/NEJM200103083441005.

7. Wallace ZS, Deshpande V, Mattoo H et al. IgG4-related disease: clinical and laboratory features in one hundred twenty-five patients. Arthritis Rheumatol 2015; 67 (9): 2466–2475. doi: 10.1002/art.39205.

8. Inoue D, Yoshida K, Yoneda N et al. IgG4-related disease: dataset of 235 consecutive patients. Medicine (Baltimore) 2015; 94 (15): e680. doi: 10.1097/MD.0000000000000 680.

9. Mikulová Š, Jílek D, Richter J. Nemoc asociovaná s IgG4: klinický obraz, orgánová postižení a terapie; 2. část. Alergie 2015; 17 (2): 92–99.

10. Abraham M, Khosroshahi A. Diagnostic and treatment workup for IgG4-related disease. Expert Rev Clin Immunol 2017; 13 (9): 867–875. doi: 10.1080/1744666X.2017.1354698.

11. Stone JH, Khosroshahi A, Deshpande V et al. Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum 2012; 64 (10): 3061–3067. doi: 10.1002/art.34593.

12. Umehara H, Okazaki K, Kawa S et al. The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD. Mod Rheumatol 2021; 31 (3): 529–533. doi: 10.1080/14397595.2020.1859710.

13. Urban ML, Palmisano A, Nicastro M et al. Idiopathic and secondary forms of retroperitoneal fibrosis: a diagnostic approach. Rev Med Interne 2015; 36 (1): 15–21. doi: 10.1016/j.revmed.2014.10.008.

14. Wallace ZS, Naden RP, Chari S et al. The 2019 American college of rheumatology/European league against rheumatism classification criteria for IgG4-related disease. Ann Rheum Dis 2020; 79 (1): 77–87. doi: 10.1136/annrheumdis-2019-216561.

15. Wallace ZS, Perugino C, Matza M et al. Immunoglobulin G4-related disease. Clin Chest Med 2019; 40 (3): 583–597. doi: 10.1016/j. ccm.2019.05.005.

16. Ozawa M, Fujinaga Y, Asano J et al. Clinical features of IgG4-related periaortitis/periarteritis based on the analysis of 179 patients with IgG4-related disease: a case-control study. Arthritis Res Ther 2017; 19 (1): 223. doi: 10.1186/s13075-017-1432-8.

17. Saeki T, Nishi S, Imai N et al. Clinicopathological characteristics of patients with IgG4-related tubulointerstitial nephritis. Kidney Int 2010; 78 (10): 1016–1023. doi: 10.1038/ki.2010.271.

18. Lanzillotta M, Mancuso G, Della-Torre E. Advances in the diagnosis and management of IgG4 related disease. BMJ 2020; 369: m1067. doi: 10.1136/bmj.m1067.

19. Kamekura R, Takahashi H, Ichimiya S. New insights into IgG4-related disease: emerging new CD4+ T-cell subsets. Curr Opin Rheumatol 2019; 31 (1): 9–15. doi: 10.1097/BOR.0000000000000558.

20. Su Y, Sun W, Wang C et al. Detection of serum IgG4 levels in patients with IgG4-related disease and other disorders. PLoS One 2015; 10 (4): e0124233. doi: 10.1371/journal.pone.0124233.

21. Culver EL, Sadler R, Simpson D et al. Elevated serum IgG4 levels in diagnosis, treatment response, organ involvement, and relapse in a prospective IgG4-related disease UK cohort. Am J Gastroenterol 2016; 111 (5): 733–743. doi: 10.1038/ajg.2016.40.

22. Tang J, Cai S, Ye C et al. Biomarkers in IgG4-related disease: a systematic review. Semin Arthritis Rheum 2020; 50 (2): 354–359. doi: 10.1016/j.semarthrit.2019.06.018.

23. Culver EL, Sadler R, Bateman AC et al. Increases in IgE, eosinophils, and mast cells can be used in diagnosis and to predict relapse of IgG4-related disease. Clin Gastroenterol Hepatol 2017; 15 (9): 1444–1452. doi: 10.1016/j.cgh.2017.02.007.

24. Chan ASY, Mudhar H, Shen SY et al. Serum IgG2 and tissue IgG2 plasma cell elevation in orbital IgG4-related disease (IgG4-RD): potential use in IgG4-RD assessment. Br J Ophthalmol 2017; 101 (11): 1576–1582. doi: 10.1136/bjophthalmol-2017-310148.

25. Karim AF, Eurelings LEM, Bansie RD et al. Soluble interleukin-2 receptor: a potential marker for monitoring disease activity in IgG4-related disease. Mediators Inflamm 2018; 2018: 6103064. doi: 10.1155/2018/6103064.

26. Wallace ZS, Mattoo H, Carruthers M et al. Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations. Ann Rheum Dis 2015; 74 (1): 190–195. doi: 10.1136/annrheumdis-2014-205233

27. Karim AF, Bansie RD, Rombach SM et al. The treatment outcomes in IgG4-related disease. Neth J Med 2018; 76 (6): 275–285.

28. Adam Z, Chovancová Z, Nová M et al. Remission of the disease associated/related with immunoglobulin IgG4 accompanied by multiple lymphadenopathy after treatment with rituximab and dexamethasone: a case report. Vnitr Lek 2018; 64 (3): 290–299.

29. Khosroshahi A, Bloch DB, Deshpande V et al. Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-related systemic disease. Arthritis Rheum 2010; 62 (6): 1755–1762. doi: 10.1002/art.27435.

30. Perugino CA, Stone JH. Treatment of IgG4-related disease: current and future approaches. Z Rheumatol 2016; 75 (7): 681–686. doi: 10.1007/s00393-016-0142-y.

31. Omar D, Chen Y, Cong Y et al. Glucocorticoids and steroid sparing medications monotherapies or in combination for IgG4-RD: a systematic review and network meta-analysis. Rheumatology (Oxford) 2020; 59 (4): 718–726. doi: 10.1093/rheumatology/kez380.

32. Sica A, Casale B, Spada A et al. Differential diagnosis: retroperitoneal fibrosis and oncological diseases. Open Med (Wars) 2018; 15: 22–26. doi: 10.1515/med-2020-0005.

33. Bertoglio P, Viti A, Paiano S et al. IgG4-related disease: a new challenging diagnosis mimicking lung cancer. Interact Cardiovasc Thorac Surg 2019; 28 (3): 410–412. doi: 10.1093/icvts/ivy279.

34. Sulieman I, Mahfouz A, AlKuwari E et al. IgG4-related disease mimicking pancreatic cancer: case report and review of the literature. Int J Surg Case Rep 2018; 50: 100–105. doi: 10.1016/j.ijscr.2018.07.030.

35. Wang Y, Chen X, Luo R et al. IgG4-related systemic disease mimicking renal pelvic cancer: a rare case. World J Surg Oncol 2014; 12: 395. doi: 10.1186/1477-7819-12-395.

36. Ichinokawa M, Matsumoto J, Kuraya T et al. A rare case of localized IgG4-related sclerosing cholecystitis mimicking gallbladder cancer. J Rural Med 2019; 14 (1): 138–142. doi: 10.2185/jrm.2998.

37. Hwang SM, Paik JH, Lee JY. ImmunoglobulinG4-related disease mimicking lymphoma. Ann Hematol 2019; 98 (9): 2239–2241. doi: 10.1007/s00277-019-03725-8.

38. Poo SX, Tham CSW, Smith C et al. IgG4-related disease in a multi-ethnic community: clinical characteristics and association with malignancy. QJM 2019; 112 (10): 763–769. doi: 10.1093/qjmed/hcz149.

39. Sekiguchi H, Horie R, Kanai M et al. IgG4-related disease: retrospective analysis of one hundred sixty-six patients. Arthritis Rheumatol 2016; 68 (9): 2290–2299. doi: 10.1002/art.39686.

40. Tang H, Yang H, Zhang P et al. Malignancy and IgG4--related disease: the incidence, related factors and prognosis from a prospective cohort study in China. Sci Rep 2020; 10 (1): 4910. doi: 10.1038/s41598-020-61585-z.

41. Asano J, Watanabe T, Oguchi T et al. Association between immunoglobulin G4-related disease and malignancy within 12 years after diagnosis: an analysis after longterm followup. J Rheumatol 2015; 42 (11): 2135–2142. doi: 10.3899/jrheum.150436.

42. Yamamoto M, Takahashi H, Tabeya T et al. Risk of malignancies in IgG4-related disease. Mod Rheumatol 2012; 22 (3): 414–418. doi: 10.1007/s10165-011-0520-x.

43. Ahn SS, Song JJ, Park YB et al. Malignancies in Korean patients with immunoglobulin G4-related disease. Int J Rheum Dis 2017; 20 (8): 1028–1035. doi: 10.1111/1756-185X.13093.

44. Hirano K, Tada M, Sasahira N et al. Incidence of malignancies in patients with IgG4-related disease. Intern Med 2014; 53 (3): 171–176. doi: 10.2169/internalmedicine.53.1342.

45. Fernández-Codina A, Martínez-Valle F, Pinilla B et al. IgG4-related disease: results from a multicenter Spanish registry. Medicine (Baltimore) 2015; 94 (32): e1275. doi: 10.1097/MD.0000000000001275.

46. Wallace ZS, Wallace CJ, Lu N et al. Association of IgG4--related disease with history of malignancy. Arthritis Rheumatol 2016; 68 (9): 2283–2289. doi: 10.1002/art.39773.

47. Bozzalla Cassione E, Stone JH. IgG4-related disease. Curr Opin Rheumatol 2017; 29 (3): 223–227. doi: 10.1097/BOR.0000000000000383.

48. Ezaki T, Akatsuka S, Sanjo T et al. Symptomatic IgG4-related prostatitis simultaneously diagnosed with aggressive prostate cancer. Case Rep Urol 2020; 2020: 6045328. doi: 10.1155/2020/6045328.

49. Giat E, Ehrenfeld M, Shoenfeld Y. Cancer and autoimmune diseases. Autoimmun Rev 2017; 16 (10): 1049–1057. doi: 10.1016/j.autrev.2017.07.022.

50. Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol 2014; 5: 520. doi: 10.3389/fimmu.2014.00520.

51. Lighaam LC, Rispens T. The immunobiology of immunoglobulin G4. Semin Liver Dis 2016; 36 (3): 200–215. doi: 10.1055/s-0036-1584322.

52. Crescioli S, Correa I, Karagiannis P et al. IgG4 characteristics and functions in cancer immunity. Curr Allergy Asthma Rep 2016; 16 (1): 7. doi: 10.1007/s11882-015-0580-7.

53. Bloom JW, Madanat MS, Marriott D et al. Intrachain disulfide bond in the core hinge region of human IgG4. Protein Sci 1997; 6 (2): 407–415. doi: 10.1002/pro.5560060217.

54. Rispens T, Ooijevaar-de Heer P, Bende O et al. Mechanism of immunoglobulin G4 Fab-arm exchange. J Am Chem Soc 2011; 133 (26): 10302–10311. doi: 10.1021/ja203638y.

55. Bianchini R, Karagiannis SN, Jordakieva G et al. The role of IgG4 in the fine tuning of tolerance in IgE-mediated allergy and cancer. Int J Mol Sci 2020; 21 (14): 5017. doi: 10.3390/ijms21145017.

56. Davies AM, Sutton BJ. Human IgG4: a structural perspective. Immunol Rev 2015; 268 (1): 139–159. doi: 10.1111/imr.12349.

57. Oberholzer A, Oberholzer C, Moldawer LL. Cytokine signaling – regulation of the immune response in normal and critically ill states. Crit Care Med 2000; 28 (4 Suppl): N3–12. doi: 10.1097/00003246-200004001-00002.

58. Suzuki K. Chronic inflammation as an immunological abnormality and effectiveness of exercise. Biomolecules 2019; 9 (6): 223. doi: 10.3390/biom9060223.

59. Singh N, Baby D, Rajguru JP et al. Inflammation and cancer. Ann Afr Med 2019; 18 (3): 121–126. doi: 10.4103/aam.aam_56_18.

60. Galli SJ, Tsai M, Piliponsky AM. The development of allergic inflammation. Nature 2008; 454 (7203): 445–454. doi: 10.1038/nature07204.

61. Arneth B. Tumor microenvironment. Medicina (Kaunas) 2019; 56 (1): 15. doi: 10.3390/medicina56010015.

62. Lei DK, Saltoun C. Allergen immunotherapy: definition, indications, and reactions. Allergy Asthma Proc 2019; 40 (6): 369–371. doi: 10.2500/aap.2019.40.4249.

63. Schatton T, Schütte U, Frank MH. Effects of malignant melanoma initiating cells on T-cell activation. Methods Mol Biol 2016; 20: 10.1007/7651_2015_299. doi: 10.1007/7651_2015_299.

64. Itakura E, Huang RR, Wen DR et al. IL-10 expression by primary tumor cells correlates with melanoma progression from radial to vertical growth phase and development of metastatic competence. Mod Pathol 2011; 24 (6): 801–809. doi: 10.1038/modpathol.2011.5.

65. Liu Q, Niu Z, Li Y et al. Immunoglobulin G4 (IgG4) -positive plasma cell infiltration is associated with the clinicopathologic traits and prognosis of pancreatic cancer after curative resection. Cancer Immunol Immunother 2016; 65 (8): 931–940. doi: 10.1007/s00262-016- 1853-2.

66. Karagiannis P, Villanova F, Josephs DH et al. Elevated IgG4 in patient circulation is associated with the risk of disease progression in melanoma. Oncoimmunology 2015; 4 (11): e1032492. doi: 10.1080/ 2162402X.2015.1032492.

67. Miyatani K, Saito H, Murakami Y et al. A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis. Virchows Arch 2016; 468 (5): 549–557. doi: 10.1007/s00428-016-1914-0.

68. Harada K, Nakanuma Y. Cholangiocarcinoma with respect to IgG4 reaction. Int J Hepatol 2014; 2014: 803876. doi: 10.1155/2014/803876.

69. Salah A, Li Y, Wang H et al. Macrophages as a double-edged weapon: the use of macrophages in cancer immunotherapy and understanding the cross-talk between macrophages and cancer. DNA Cell Biol 2021; 40 (3): 429–440. doi: 10.1089/dna.2020.6087.

70. Bianchini R, Roth-Walter F, Ohradanova-Repic A et al. IgG4 drives M2a macrophages to a regulatory M2b-like phenotype: potential implication in immune tolerance. Allergy 2019; 74 (3): 483–494. doi: 10.1111/all.13635.

71. Shimosegawa T, Chari ST, Frulloni L et al. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas 2011; 40 (3): 352–358. doi: 10.1097/MPA.0b013e3182142fd2.

72. Kamisawa T, Nakazawa T, Tazuma S et al. Clinical practice guidelines for IgG4-related sclerosing cholangitis. J Hepatobiliary Pancreat Sci 2019; 26 (1): 9–42. doi: 10.1002/jhbp.596.

73. Mizushima I, Kasashima S, Fujinaga Y et al. Clinical and pathological characteristics of IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis diagnosed based on experts‘ diagnosis. Ann Vasc Dis 2019; 12 (4): 460–472. doi: 10.3400/avd.oa.19-00085.

74. Carruthers MN, Khosroshahi A, Augustin T et al. The diagnostic utility of serum IgG4 concentrations in IgG4--related disease. Ann Rheum Dis 2015; 74 (1): 14–18. doi: 10.1136/annrheumdis-2013-204907.

75. Kawano M, Saeki T, Nakashima H et al. Proposal for diag- nostic criteria for IgG4-related kidney disease. Clin Exp Nephrol 2011; 15 (5): 615–626. doi: 10.1007/s10157-011-0521-2.

76. Goto H, Takahira M, Azumi A et al. Diagnostic criteria for IgG4-related ophthalmic disease. Jpn J Ophthalmol 2015; 59 (1): 1–7. doi: 10.1007/s10384-014-0352-2.

77. Matsui S, Yamamoto H, Minamoto S et al. Proposed diagnostic criteria for IgG4-related respiratory disease. Respir Investig 2016; 54 (2): 130–132. doi: 10.1016/j.resinv.2015.09.002.

78. Bashyam A, Nagala S, Tahir F et al. Immunoglobulin G4-related disease of the paranasal sinuses. BMJ Case Rep 2018; 2018: bcr2018224472. doi: 10.1136/bcr-2018-224472.

79. Lee LIT, Gillibrand R, Mukerjee D et al. Isolated pulmonary IgG4-related disease mimicking lung malignancy. BJR Case Rep 2017; 3 (3): 20160134. doi: 10.1259/bjrcr.20160134.

80. Lococo F, Di Stefano T, Rapicetta C et al. Thoracic hyper-IgG4-related disease mimicking malignant pleural mesothelioma. Lung 2019; 197 (3): 387–390. doi: 10.1007/s00408-019-00224-5.

81. Tsuda B, Kumaki N, Ishida R et al. Distinction of IgG4--related mastitis from breast cancer: a case report. Surg Case Rep 2019; 5 (1): 123. doi: 10.1186/s40792-019- 0681-y.

82. Jearth V, Patil P, Patkar S et al. Immunoglobulin G4--related cholecystitis mimicking a locally advanced gallbladder cancer-a case report and review of literature. Clin J Gastroenterol 2020; 13 (5): 806–811. doi: 10.1007/s12328-020-01168-7.

83. Rungsakulkij N, Sornmayura P, Tannaphai P. Isolated IgG4-related sclerosing cholangitis misdiagnosed as malignancy in an area with endemic cholangiocarcinoma: a case report. BMC Surg 2017; 17 (1): 17. doi: 10.1186/s12893-017-0214-1.

84. Lei WH, Xin J, Shao CX et al. IgG4-related kidney disease mimicking malignant ureter tumor: case report and literature review. Medicine (Baltimore) 2016; 95 (3): e2550. doi: 10.1097/MD.0000000000002 550.

85. Dum TW, Zhang D, Lee EK. IgG4-related disease in a urachal tumor. Case Rep Urol 2014; 2014: 275850. doi: 10.1155/2014/275850.