Persistent Circulating Immune Complexes: Potential Source of Epimutation and Cancer Poor Prognosis
International Journal of Genetics and Genomics
Volume 5, Issue 1, February 2017, Pages: 1-13
Received: Dec. 13, 2016; Accepted: Dec. 27, 2016; Published: Jan. 29, 2017
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Authors
Michael Chukwudi Ezeani, Department of Immunology, Faculty of Medicine, Nnamdi Azikiwe University, Awka, Nigeria
Charles Chinedum Onyenekwe, Department of Medical Laboratory Science, Faculty of Health Sciences, Nnamdi Azikiwe University Awka, Nigeria
Samuel Chukwuemeka Meludu, Department of Human Biochemistry, Faculty of Basic Medical Sciences, Nnamdi Azikiwe University Awka, Nigeria
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Abstract
Estimation of serum level of circulating immune complexes and its use for monitoring treatments have been carried out extensively in various disease conditions including autoimmune diseases and cancer, but little or no work has considered persistent circulation of immune complexes consequent to physiological anomalies that could mediate epimutation and subsequent epigenetic cell alteration and tumourigenesis. This review looked into the immuno-physiological activities of circulating immune complexes to expose its possible epigenomic consequences and potential role in epimutation. The environmental link between epigenetic cell alteration and formation of circulating immune complexes makes this review a unique one but on the other hand, gives room for concern. Immune complexes have strong capacity to stimulate various immune responses, yet the immunological activities of these circulating immune complexes are over looked or under estimated. Immune complexes is a normal immunological phenomenon but its persistence and subsequent deposition could induce endogenous assaults that would continuously and adversely perturb the epigenomic activities by fuelling chronic inflammation, activating transcription factors (NFkB), generation of reactive oxygen species (ROS) and frequent release of cytokines leading to epigenetic cell alteration especially in developing countries where environmental pollution is a serious factor.
Keywords
Circulating Immune Complexes, Epimutation, Epigenome, Persistence, Poor Prognosis, Tumourigenesis, Cancer
To cite this article
Michael Chukwudi Ezeani, Charles Chinedum Onyenekwe, Samuel Chukwuemeka Meludu, Persistent Circulating Immune Complexes: Potential Source of Epimutation and Cancer Poor Prognosis, International Journal of Genetics and Genomics. Vol. 5, No. 1, 2017, pp. 1-13. doi: 10.11648/j.ijgg.20170501.11
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Copyright © 2017 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
References
[1]
Shmagel & cheresshnev. Molecular bases of immune complex pathology. Biochem (Moscow) 74, 469-479 (2009).
[2]
Onyenekwe CC, Arinola OG, Salimolu SL. Total protein, circulating immune complexes levels and degree of parasitaemia in plasmodium berghei infected protein deficient experimental animals. J. Med. Lab. Sci2000; 9: 1-10.
[3]
Golda R, Wolski Z, Wyszomirska GM, Madalinski K, Michalkiewicz J. The presence and structure of circulating immune complexes in patients with prostate tumors. Med. Sci. Monit 2004; 10: 23-7.
[4]
Matchin AA, Smoliagin AI. A comparative evaluation of immune status of patients with squamous cell cancer of oral mucosa at different stages of combined treatment. Stomatologiia 2000; 79: 29-32.
[5]
Cynthia J, Nerurkar A. V.& Karjodkar F. R. Circulating Immune Complexes (Cic) As Marker For Disease Progress In Oral Cancer. Indian J. Clini. Biochem 2007; 22: 114 117.
[6]
Kelley MC. Tumor associated antigen TA-90 immune complex assay predicts subclinical metastasis and survival for patients with early stage melanoma. Cancer 1998; 83: 1355-1361.
[7]
Shalu R, Mody RN. Serum circulating immune complexes as prognostic indicators in premalignant and malignant lesions of oral cavity during and following radiotherapy. J. Can. Res. Ther 2012; 8: 116-122.
[8]
Anand, P, et al., Cancer is a preventable disease that requires major lifestyle changes. Pharmaceutical Res. 2007; 25: 2097–116.
[9]
Ferrari S. Persistence of circulating ADAMTS13-specific immune complexes in patients with acquired thrombotic thrombocytopenic purpura. Haematologica. 2013; 984151.
[10]
Ezeani MC. et al. Aerobacteriology of laboratories and offices: Evidence of high riskexposure to immune complex formation in Nigeria. Asian Pacific J. Trop. Dis. 2011; 131-136.
[11]
Toong C, Adelstein S, Phan TG. Clearing the complexity: immune complexes and their treatment in lupus nephritis. Int J Nephrol Renovasc Dis. 2011; 4: 17-28.
[12]
Poon IKH, Christopher DL, Adriano GR, Kodi SR. (2014). Apoptotic cell clearance: basic biology and therapeutic potential. Nature Review Immunology 14(3): 166–180
[13]
Rafik Salama, Mahito Sadaie, Matthew Hoare, and Masashi Narita, Cellular senescence and its effector programs Genes & Dev. 2014. 28: 99-114
[14]
Hassan Mohamed, Hidemichi Watari, Ali AbuAlmaaty. Yusuke Ohba, Noriaki Sakuragi Apoptosis and Molecular Targeting Therapy in Cancer Biomed Res Int. 2014; 2014: 150845.
[15]
Srikrishna G, Freeze HH. Endogenous damage-associated molecular pattern molecules at the crossroads of inflammation and cancer. Neoplasia2009; 11(7):615-28.
[16]
Stelekati E, Wherry EJ. Chronic bystander infections and immunity to unrelated antigens. Cell Host Micro 2012; 12(4): 458–469.
[17]
Stelekati E, Haina S, Travis AD, Douglas VD, Carly GZ, Daniel PB, Lucas D, Jennifer L, David W, Mohammed-Alkhatim AA, Peter DK, Hao S, David SR, Haining WN, Georg ML, Wherry EJ.Bystander Chronic Infection Negatively Impacts Development of CD8+ T Cell Memory. Immunity 2014; 40(5):801–813.
[18]
Coveney AP, Wei W, Justin K, Jing HL, Siobhan B, Qiong DW, Redmond HP, Jiang HW. Myeloid-related protein 8 induces self-tolerance and cross-tolerance to bacterial infection via TLR4- and TLR2-mediated signal pathways. Sci. Rep 2015; 5: 13694.
[19]
Rojko JL, Evans MG, Price SA, Han B, Waine G, DeWitte M, Haynes J, Freimark B, Martin P, Raymond JT, Evering W, Rebelatto MC, Schenck E, Horvath C. Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes. Toxicologic Pathology (2014). 42 (4): 725-
[20]
Steven and Swanson Detection of Immune Complex Formation in Non-Clinical Studies and Implications for Clinical Risk Assessment Medical Sciences/Clinical Immunologyswanson@amgen.com
[21]
Mart M. Pathophysiology of circulating immune complexes. arthritis and rheuma 1982; 25: 783 (1982).
[22]
Chelsey L, Goins CP, Chappell RS, Periasamy S, Joshy J. Immune Complex-Mediated Enhancement of Secondary Antibody Responses. J. Immunol. 2010; 184: 6293-6298.
[23]
Jiang K, Chen Y, Xu CS, Javin JN. T cell activation by soluble C1q-bearing immune complexes: implications for the pathogenesis of rheumatoid arthritis. Clin Exp Immunol 2003;131: 61–67.
[24]
Jürg AS, Ronald PT. Physiological and pathological aspects of circulating immune complexes. Kidney Inter 1989; 35: 993–1003.
[25]
Ouaissi A. Regulatory Cells and Immunosuppressive Cytokines: Parasite-Derived Factors Induce Immune Polarization. J Biomed Biotechnol. 2007; 2007: 94971.
[26]
Evangelina A, Laborde S, Vanzulli M, Beigier-Bompadre MA, Isturiz RA, Ruggiero MG et al.,Immune Complexes Inhibit Differentiation, Maturation, and Function of Human Monocyte-Derived Dendritic Cells. J. Immunol 2007; 179: 673-681.
[27]
Stokol T, O'Donnell P, Xiao L, Knight S, Stavrakis G, Botto M. C1q governs deposition of circulating immune complexes and leukocyte Fc gamma receptors mediate subsequent neutrophil recruitment. J. Exp. Med2004; 200: 835–846.
[28]
Tanya NM, George CT, Naotake T. Mechanisms of Immune Complex–Mediated Neutrophil Recruitment and Tissue Injury. Cir 2009; 120: 2012-2024.
[29]
Ji H, Ohmura K, Mahmood U, Lee DM, Hofhuis FM, Boackle SA, Takahashi K Arthritis critically dependent on innate immune system players. Immunity. 2002; 16: 157–168.
[30]
Rönnelid J, Ahlin E, Nilsson B, Nilsson-Ekdahl K Mathsson L. Immune complex-mediated cytokine production is regulated by classical complement activation both in vivo and in vitro. Adv Exp Med Biol. 2008; 632: 187-201.
[31]
Kumar RK, Wakefield D. Inflammation: Chronic. In: eLS. John Wiley & Sons Ltd, Chichester 2015 [doi: 10.1002/9780470015902.a0000944.pub4.
[32]
Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008; 454: 428–435.
[33]
Metz M, Grimbaldeston MA, Nakae S, Piliponsky AM, Tsai M, Galli SJ. "Mast cells in the promotion and limitation of chronic inflammation." Immunol Rev 2007; 217: 304-328.
[34]
Naugler WE, Karin M. The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer. Trends Mol Med. 2008;14: 109–119
[35]
Wu YSA, Meitzler JL and Doroshow JH. Molecular mechanisms underlying chronic inflammation-associated cancers Cancer Lett. 2014; 345 (2): 164–173.
[36]
Meira LB, Bugni JM, Green SL, Lee C, Pang B, Borenshtein D. DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice. J Clin Invest. 2008; 118 (7): 2516–2525.
[37]
Jancar S, Sánchez CM. Immune complex-mediated tissue injury: a multistep paradigm. Trends Immunol 2005; 26: 48-55.
[38]
Feldmann M., Pusey CD. Is there a role for TNF-α in anti-neutrophil cytoplasmic antibody-associated vasculitis? Lessons from other chronic inflammatory diseases J. Am. Soc. Nephrol 2006; 17: 1243-1252.
[39]
Nimmerjahn F, Ravetch JV. Fcgamma receptors as regulators of immune responses. Nat Rev Immunol 2008;8: 34–47.
[40]
Kaihong S, Hengxuan Y, Xinrui L, Xiaoli L, Andrew WG, John MC et al., Expression Profile of FcγRIIb on Leukocytes and Its Dysregulation in Systemic Lupus Erythematosus J Immunol. 2007; 178 (5): 3272–3280.
[41]
Zhu T, Chen R, Li Z, Tian J, Deng C, Zhang X et al., Functional Role of FcγRIIB in the Regulation of Mesenchymal Stem Cell Function. Int J Med Sci. 2016; 13 (2): 154–160.
[42]
Schmidt RE, Gessner JE. Fc receptors and their interaction with complement in autoimmunity. Immunol Lett. 2005; 100: 56–67.
[43]
Bao L, Cunningham PN and Quigg RJ. The complement system in lupus nephritis F1000 Research 2015, 4: 145
[44]
Lauterbach, M., O'Donnell, P., Asano, K., Mayadas. T. N. Role of TNF priming and adhesion molecules in neutrophil recruitment to intravascular immune complexes. J. Leukoc. Biol. 2008; 83: 1423–1430.
[45]
Corda S, Laplace C, Vicaut E, Duranteau J. Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor-alpha is mediated by ceramide. Am. J. Respir. Cell Mol. Biol 2001; 24: 762–768.
[46]
Chen X, Andresen BT, Hill M, Zhang J, Booth F, Zhang C. Role of reactive oxygen species in tumor necrosis factor-alpha induced endothelial dysfunction. Curr. Hypertens. Rev 2008; 4: 245–255.
[47]
Natarajan M, Gibbons CF, Mohan S, Moore S, Kadhim MA. Oxidative stress signaling: a potential mediator of tumour necrosis factor {alpha}-induced genomic instability in primary vascular endothelial cells. Br. J. Radiol2007; 80: 13–22.
[48]
Westbrook AM, Wei B, Hacke K, Xia M, Braun J, Schiest RH. The role of tumour necrosis factor-a and tumour necrosis factor receptor signalling in inflammation-associated systemic genotoxicity. Mutagenesis. 27, 77–86 (2012).
[49]
Karin M, Greten FR. NF-κB: linking inflammation and immunity to cancer development and progression. Nat. Rev 2005; 5: 749-759.
[50]
Karin M, Cao Y, Greten FR, Li ZW. NF-κB in cancer: from innocent bystander to major culprit. Nat. Rev. Can. 2002; 2 (4): 301-310.
[51]
Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ et al., IKK beta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 2004; 118: 285-296.
[52]
Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S et al. NF-κB functions as a tumor promoter in inflammation-associated cancer. Nature 2004; 43: 461-466.
[53]
Häcker H, Karin M. Regulation and function of IKK and IKK-related kinases. Sci STKE 2006; 357: 13.
[54]
Pacifico F, Leonardi A. NF-κB in solid tumors. Biochem Pharmacol 2006; 72: 1142-1152.
[55]
Karin M. NF-κB and cancer: mechanisms and targets. Mol Carcinogenesis 2006; 45 (6): 355-361.
[56]
Malkin, D. (2011). "Li-Fraumeni Syndrome" Genes & Cancer. 2 (4): 475–484.
[57]
Hoesel B, and Schmid JA. Molecular Cancer 2013 The complexity of NF-κB signaling in inflammation and cancer
[58]
Fossati G, Bucknall RC, Edwards SW. Insoluble and soluble immune complexes activate neutrophils by distinct activation mechanisms: changes in functional responses induced by priming with cytokines Ann Rheum Dis 2002; 61: 13–19.
[59]
Wiseman H, Halliwell B. Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer Biochem. J. 1996; 313: 17-29.
[60]
Nebert DW, Roe AL, Dieter MZ, Solis WA, Yang Y, Dalton TP. Role of the aromatic hydrocarbon receptor and [Ah] gene battery in the oxidative stress response, cell cycle control, and apoptosis. Biochemical Pharmacology Volume 59, Issue 1, 1 January 2000, Pages 65–85.
[61]
Schreck R, Albermann K, Baeuerle PA. Nuclear factor kappa B: an oxidative stress-responsive transcription factor of eukaryotic cells (a review). Free Radic Res Commun. 1992; 17 (4): 221–237.
[62]
Chahwan R, Wontakal SN, Roa S. "The multi-dimensional nature of epigenetic information and its role in disease". Discov Med. 2011; 11 (58): 233–43.
[63]
Wyatt MD, Pittman DL. Methylating agents and DNA repair responses: Methylated bases and sources of strand breaks. Chem. Res. Toxicol. 2006; 19: 1580-1594.
[64]
Totter JR. Spontaneous cancer and its pos¬sible relationship to oxygen metabolism. Proc. Nat. Acad. Sci. U. S. A. 1980; 77: 1763-1767.
[65]
Ohshima H, Bartsch H Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. Mutat Res. 1994 Mar 1; 305 (2): 253-64.
[66]
Box HC, Freund HG, Budzinski E, Wallace JC, Maccubbin AE. Free Radical-Induced Double Base Lesions. Radiat. Res 1995; 141: 91-94.
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