Antibodies against endogenous retroviruses.

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      Publisher: Blackwell Country of Publication: England NLM ID: 7702118 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1600-065X (Electronic) Linking ISSN: 01052896 NLM ISO Abbreviation: Immunol Rev Subsets: MEDLINE
    • Publication Information:
      Publication: <2002-> : Oxford : Blackwell
      Original Publication: Copenhagen, Munksgaard.
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    • Abstract:
      The human genome harbors hundreds of thousands of integrations of ancient retroviruses, amassed over millions of years of evolution. To reduce further amplification in the genome, the host prevents transcription of these now endogenous retroviruses (ERVs) through epigenetic repression and, with evolutionary time, ERVs are incapacitated by accumulating mutations and deletions. However, several members of recently endogenized ERV groups still retain the capacity to produce viral RNA, retroviral proteins, and higher order structures, including virions. The retention of viral characteristics, combined with the reversible nature of epigenetic repression, particularly as seen in cancer, allow for immunologically unanticipated ERV expression, perceived by the adaptive immune system as a genuine retroviral infection, to which it has to respond. Accordingly, antibodies reactive with ERV antigens have been detected in diverse disorders and, occasionally, in healthy individuals. Although they are part of self, the retroviral legacy of ERV antigens, and association with and, possibly, causation of disease states may set them apart from typical self-antigens. Consequently, the pathogenic or, indeed, host-protective capacity of antibodies targeting ERV antigens is likely to be context-dependent. Here, we review the immunogenicity of typical ERV proteins, with emphasis on the antibody response and its potential disease implications.
      (© 2024 The Author(s). Immunological Reviews published by John Wiley & Sons Ltd.)
    • References:
      Aiewsakun P, Katzourakis A. Marine origin of retroviruses in the early Palaeozoic Era. Nat Commun. 2017;8:13954.
      Bannert N, Kurth R. The evolutionary dynamics of human endogenous retroviral families. Annu Rev Genomics Hum Genet. 2006;7:149‐173.
      Kassiotis G, Stoye JP. Immune responses to endogenous retroelements: taking the bad with the good. Nat Rev Immunol. 2016;16(4):207‐219.
      Johnson WE. Origins and evolutionary consequences of ancient endogenous retroviruses. Nat Rev Microbiol. 2019;17(6):355‐370.
      Hoyt SJ, Storer JM, Hartley GA, et al. From telomere to telomere: the transcriptional and epigenetic state of human repeat elements. Science. 2022;376(6588):eabk3112.
      Dopkins N, Nixon DF. Activation of human endogenous retroviruses and its physiological consequences. Nat Rev Mol Cell Biol. 2024;25(3):212‐222.
      Kassiotis G. The immunological conundrum of endogenous retroelements. Annu Rev Immunol. 2023;41:99‐125.
      George M, Schwecke T, Beimforde N, et al. Identification of the protease cleavage sites in a reconstituted gag polyprotein of an HERV‐K (HML‐2) element. Retrovirology. 2011;8:30.
      Yang J, Bogerd HP, Peng S, Wiegand H, Truant R, Cullen BR. An ancient family of human endogenous retroviruses encodes a functional homolog of the HIV‐1 rev protein. Proc Natl Acad Sci USA. 1999;96(23):13404‐13408.
      Mayer J, Meese EU. Presence of dUTPase in the various human endogenous retrovirus K (HERV‐K) families. J Mol Evol. 2003;57(6):642‐649.
      Armbruester V, Sauter M, Krautkraemer E, Meese E, Kleiman A, Best B. A novel gene from the human endogenous retrovirus K expressed in transformed cells. Clin Cancer Res. 2002;8:1800‐1807.
      Chen T, Meng Z, Gan Y, et al. The viral oncogene Np9 acts as a critical molecular switch for co‐activating β‐catenin, ERK, Akt and Notch1 and promoting the growth of human leukemia stem/progenitor cells. Leukemia. 2013;27(7):1469‐1478.
      Dewannieux M, Blaise S, Heidmann T. Identification of a functional envelope protein from the HERV‐K family of human endogenous retroviruses. J Virol. 2005;79(24):15573‐15577.
      Hanke K, Kramer P, Seeher S, Beimforde N, Kurth R, Bannert N. Reconstitution of the ancestral glycoprotein of human endogenous retrovirus k and modulation of its functional activity by truncation of the cytoplasmic domain. J Virol. 2009;83(24):12790‐12800.
      Gröger V, Wieland L, Naumann M, et al. Formation of HERV‐K and HERV‐Fc1 envelope family members is suppressed on transcriptional and translational level. Int J Mol Sci. 2020;21(21):7855.
      Dewannieux M, Harper F, Richaud A, Letzelter C, Ribet D, Pierron G. Identification of an infectious progenitor for the multiple‐copy HERV‐K human endogenous retroelements. Genome Res. 2006;16:1548‐1556.
      Vogetseder W, Dumfahrt A, Mayersbach P, Schonitzer D, Dierich MP. Antibodies in human sera recognizing a recombinant outer membrane protein encoded by the envelope gene of the human endogenous retrovirus K. AIDS Res Hum Retrovir. 1993;9:687‐694.
      Denner J, Phelps RC, Löwer J, Lower R, Kurth R. Antibody response of pregnant women, tumor and AIDS patients against the human endogenous retrovirus HERV‐K. J Cancer Res Clin Oncol. 1995;121(1):S5.
      Sauter M, Schommer S, Kremmer E, et al. Human endogenous retrovirus K10: expression of gag protein and detection of antibodies in patients with seminomas. J Virol. 1995;69(1):414‐421.
      Boller K, Janssen O, Schuldes H, Tonjes RR, Kurth R. Characterization of the antibody response specific for the human endogenous retrovirus HTDV/HERV‐K. J Virol. 1997;71:4581‐4588.
      Hishikawa T, Ogasawara H, Kaneko H, et al. Detection of antibodies to a recombinant gag protein derived from human endogenous retrovirus clone 4‐1 in autoimmune diseases. Viral Immunol. 1997;10(3):137‐147.
      Herve CA, Lugli EB, Brand A, Griffiths DJ, Venables PJ. Autoantibodies to human endogenous retrovirus‐K are frequently detected in health and disease and react with multiple epitopes. Clin Exp Immunol. 2002;128(1):75‐82.
      Christensen T, Sørensen PD, Hansen HJ, Møller‐Larsen A. Antibodies against a human endogenous retrovirus and the preponderance of Env splice variants in multiple sclerosis patients. Mult Scler. 2003;9(1):6‐15.
      Kleiman A, Senyuta N, Tryakin A, et al. HERV‐K (HML‐2) GAG/ENV antibodies as indicator for therapy effect in patients with germ cell tumors. Int J Cancer. 2004;110(3):459‐461.
      Buscher K, Trefzer U, Hofmann M, Sterry W, Kurth R, Denner J. Expression of human endogenous retrovirus K in melanomas and melanoma cell lines. Cancer Res. 2005;65(10):4172‐4180.
      Humer J, Waltenberger A, Grassauer A, et al. Identification of a melanoma marker derived from melanoma‐associated endogenous retroviruses. Cancer Res. 2006;66(3):1658‐1663.
      Wang‐Johanning F, Liu J, Rycaj K, et al. Expression of multiple human endogenous retrovirus surface envelope proteins in ovarian cancer. Int J Cancer. 2007;120(1):81‐90.
      Hahn S, Ugurel S, Hanschmann KM, et al. Serological response to human endogenous retrovirus K in melanoma patients correlates with survival probability. AIDS Res Hum Retrovir. 2008;24(5):717‐723.
      Brudek T, Christensen T, Aagaard L, Petersen T, Hansen HJ, Møller‐Larsen A. B cells and monocytes from patients with active multiple sclerosis exhibit increased surface expression of both HERV‐H Env and HERV‐W Env, accompanied by increased seroreactivity. Retrovirology. 2009;6:104.
      Thomas A, Perzova R, Abbott L, et al. LGL leukemia and HTLV. AIDS Res Hum Retrovir. 2010;26(1):33‐40.
      Reis BS, Jungbluth AA, Frosina D, et al. Prostate cancer progression correlates with increased humoral immune response to a human endogenous retrovirus GAG protein. Clin Cancer Res. 2013;19(22):6112‐6125.
      Perzova R, Graziano E, Sanghi S, et al. Increased seroreactivity to HERV‐K10 peptides in patients with HTLV myelopathy. Virol J. 2013;10:360.
      Wang‐Johanning F, Li M, Esteva FJ, et al. Human endogenous retrovirus type K antibodies and mRNA as serum biomarkers of early‐stage breast cancer. Int J Cancer. 2014;134(3):587‐595.
      Gupta R, Michaud HA, Zeng X, et al. Diminished humoral responses against and reduced gene expression levels of human endogenous retrovirus‐K (HERV‐K) in psoriasis. J Transl Med. 2014;12:256.
      Nelson PN, Roden D, Nevill A, et al. Rheumatoid arthritis is associated with IgG antibodies to human endogenous retrovirus gag matrix: a potential pathogenic mechanism of disease? J Rheumatol. 2014;41(10):1952‐1960.
      Perzova R, Graziano E, Sanghi S, et al. Increased seroreactivity to human T cell lymphoma/leukemia virus‐related endogenous sequence‐1 gag peptides in patients with human T cell lymphoma/leukemia virus myelopathy. AIDS Res Hum Retrovir. 2015;31(2):242‐249.
      Mameli G, Erre GL, Caggiu E, et al. Identification of a HERV‐K Env surface peptide highly recognized in rheumatoid arthritis (RA) patients: a cross‐sectional case‐control study. Clin Exp Immunol. 2017;189(1):127‐131.
      de Mulder M, SenGupta D, Deeks SG, et al. Anti‐HERV‐K (HML‐2) capsid antibody responses in HIV elite controllers. Retrovirology. 2017;14(1):41.
      Arru G, Mameli G, Deiana GA, et al. Humoral immunity response to human endogenous retroviruses K/W differentiates between amyotrophic lateral sclerosis and other neurological diseases. Eur J Neurol. 2018;25(8):1076‐e1084.
      Tokuyama M, Gunn BM, Venkataraman A, et al. Antibodies against human endogenous retrovirus K102 envelope activate neutrophils in systemic lupus erythematosus. J Exp Med. 2021;218(7):e20191766.
      Deakin CT, Cornish GH, Ng KW, et al. Favorable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases. Med (N Y). 2021;2(9):1093‐1109.e1096.
      Simula ER, Arru G, Zarbo IR, Solla P, Sechi LA. TDP‐43 and HERV‐K envelope‐specific immunogenic epitopes are recognized in ALS patients. Viruses. 2021;13(11):2301.
      Arru G, Galleri G, Deiana GA, et al. HERV‐K modulates the immune response in ALS patients. Microorganisms. 2021;9(8):1784.
      Garcia‐Montojo M, Simula ER, Fathi S, et al. Antibody response to HML‐2 may be protective in amyotrophic lateral sclerosis. Ann Neurol. 2022;92:782‐792.
      Khadjinova AI, Wang X, Laine A, et al. Autoantibodies against the envelope proteins of endogenous retroviruses K102 and K108 in patients with systemic lupus erythematosus correlate with active disease. Clin Exp Rheumatol. 2022;40(7):1306‐1312.
      Wang X, Hefton A, Ni K, et al. Autoantibodies against unmodified and citrullinated human endogenous retrovirus K envelope protein in patients with rheumatoid arthritis. J Rheumatol. 2022;49(1):26‐35.
      Lu‐Culligan A, Tabachnikova A, Pérez‐Then E, et al. No evidence of fetal defects or anti‐syncytin‐1 antibody induction following COVID‐19 mRNA vaccination. PLoS Biol. 2022;20(5):e3001506.
      Noli M, Meloni G, Ruberto S, et al. HERV‐K envelope protein induces long‐lasting production of autoantibodies in T1DM patients at onset in comparison to ZNT8 autoantibodies. Pathogens. 2022;11(10):1188.
      Manca MA, Solinas T, Simula ER, et al. HERV‐K and HERV‐H Env proteins induce a humoral response in prostate cancer patients. Pathogens. 2022;11(1):95.
      Ng KW, Boumelha J, Enfield KSS, et al. Antibodies against endogenous retroviruses promote lung cancer immunotherapy. Nature. 2023;616(7957):563‐573.
      Larouche JD, Trofimov A, Hesnard L, et al. Widespread and tissue‐specific expression of endogenous retroelements in human somatic tissues. Genome Med. 2020;12(1):40.
      Passos V, Pires AR, Foxall RB, Nunes‐Cabaço H, Sousa AE. Expression of human endogenous retroviruses in the human thymus along T cell development. Front Virol. 2022;2:2.
      Burn A, Roy F, Freeman M, Coffin JM. Widespread expression of the ancient HERV‐K (HML‐2) provirus group in normal human tissues. PLoS Biol. 2022;20(10):e3001826.
      Larouche JD, Laumont CM, Trofimov A, et al. Transposable elements regulate thymus development and function. elife. 2024;12:RP91037.
      Dopkins N, Singh B, Michael S, et al. Ribosomal profiling of human endogenous retroviruses in healthy tissues. BMC Genomics. 2024;25(1):5.
      Young GR, Ploquin MJ, Eksmond U, Wadwa M, Stoye JP, Kassiotis G. Negative selection by an endogenous retrovirus promotes a higher‐avidity CD4+ T cell response to retroviral infection. PLoS Pathog. 2012;8(5):e1002709.
      Ottina E, Levy P, Eksmond U, et al. Restoration of endogenous retrovirus infectivity impacts mouse cancer models. Cancer Immunol Res. 2018;6(11):1292‐1300.
      Simpson E, Takacs K, Altmann DM. Thymic repertoire selection by superantigens: presentation by human and mouse MHC molecules. Thymus. 1994;23(1):1‐13.
      Acha‐Orbea H, MacDonald HR. Superantigens of mouse mammary tumor virus. Annu Rev Immunol. 1995;13:459‐486.
      Ribot J, Romagnoli P, van Meerwijk JP. Agonist ligands expressed by thymic epithelium enhance positive selection of regulatory T lymphocytes from precursors with a normally diverse TCR repertoire. J Immunol. 2006;177(2):1101‐1107.
      Punkosdy GA, Blain M, Glass DD, et al. Regulatory T‐cell expansion during chronic viral infection is dependent on endogenous retroviral superantigens. Proc Natl Acad Sci USA. 2011;108(9):3677‐3682.
      Myers L, Joedicke JJ, Carmody AB, et al. IL‐2‐independent and TNF‐alpha‐dependent expansion of Vbeta5+ natural regulatory T cells during retrovirus infection. J Immunol. 2013;190(11):5485‐5495.
      Conrad B, Weissmahr RN, Böni J, Arcari R, Schüpbach J, Mach B. A human endogenous retroviral Superantigen as candidate autoimmune gene in type I diabetes. Cell. 1997;90(2):303‐313.
      Sutkowski N, Conrad B, Thorley‐Lawson DA, Huber BT. Epstein‐Barr virus transactivates the human endogenous retrovirus HERV‐K18 that encodes a superantigen. Immunity. 2001;15(4):579‐589.
      Meylan F, De Smedt M, Leclercq G, et al. Negative thymocyte selection to HERV‐K18 superantigens in humans. Blood. 2005;105(11):4377‐4382.
      Tai AK, Lin M, Chang F, et al. Murine Vbeta3+ and Vbeta7+ T cell subsets are specific targets for the HERV‐K18 Env superantigen. J Immunol. 2006;177(5):3178‐3184.
      Goodnow CC, Vinuesa CG, Randall KL, Mackay F, Brink R. Control systems and decision making for antibody production. Nat Immunol. 2010;11(8):681‐688.
      Nemazee D. Mechanisms of central tolerance for B cells. Nat Rev Immunol. 2017;17(5):281‐294.
      Mavrommatis B, Baudino L, Levy P, et al. Dichotomy between T cell and B cell tolerance to neonatal retroviral infection permits T cell therapy. J Immunol. 2016;197(9):3628‐3638.
      Aaronson SA, Stephenson JR. Widespread natural occurrence of high titers of neutralizing antibodies to a specific class of endogenous mouse type‐C virus. Proc Natl Acad Sci USA. 1974;71(5):1957‐1961.
      Young GR, Eksmond U, Salcedo R, Alexopoulou L, Stoye JP, Kassiotis G. Resurrection of endogenous retroviruses in antibody‐deficient mice. Nature. 2012;491(7426):774‐778.
      Yu P, Lübben W, Slomka H, et al. Nucleic acid‐sensing toll‐like receptors are essential for the control of endogenous retrovirus viremia and ERV‐induced tumors. Immunity. 2012;37(5):867‐879.
      Rauch E, Amendt T, Lopez Krol A, et al. T‐bet(+) B cells are activated by and control endogenous retroviruses through TLR‐dependent mechanisms. Nat Commun. 2024;15(1):1229.
      Toufaily C, Landry S, Leib‐Mosch C, Rassart E, Barbeau B. Activation of LTRs from different human endogenous retrovirus (HERV) families by the HTLV‐1 tax protein and T‐cell activators. Viruses. 2011;3(11):2146‐2159.
      Gonzalez‐Hernandez MJ, Swanson MD, Contreras‐Galindo R, et al. Expression of human endogenous retrovirus type K (HML‐2) is activated by the tat protein of HIV‐1. J Virol. 2012;86(15):7790‐7805.
      Gonzalez‐Hernandez MJ, Cavalcoli JD, Sartor MA, et al. Regulation of the human endogenous retrovirus K (HML‐2) transcriptome by the HIV‐1 tat protein. J Virol. 2014;88(16):8924‐8935.
      Monde K, Contreras‐Galindo R, Kaplan MH, Markovitz DM, Ono A. Human endogenous retrovirus K gag coassembles with HIV‐1 gag and reduces the release efficiency and infectivity of HIV‐1. J Virol. 2012;86(20):11194‐11208.
      Brinzevich D, Young GR, Sebra R, et al. HIV‐1 interacts with human endogenous retrovirus K (HML‐2) envelopes derived from human primary lymphocytes. J Virol. 2014;88(11):6213‐6223.
      van der Kuyl AC. HIV infection and HERV expression: a review. Retrovirology. 2012;9:6.
      Chen J, Foroozesh M, Qin Z. Transactivation of human endogenous retroviruses by tumor viruses and their functions in virus‐associated malignancies. Oncogenesis. 2019;8(1):6.
      Lee D, Le Pen J, Yatim A, et al. Inborn errors of OAS‐RNase L in SARS‐CoV‐2‐related multisystem inflammatory syndrome in children. Science. 2023;379(6632):eabo3627.
      Kassiotis G. Endogenous retroviruses and the development of cancer. J Immunol. 2014;192(4):1343‐1349.
      Hofacre A, Fan H. Jaagsiekte sheep retrovirus biology and oncogenesis. Viruses. 2010;2(12):2618‐2648.
      Kassiotis G, Stoye JP. Making a virtue of necessity: the pleiotropic role of human endogenous retroviruses in cancer. Philos Trans R Soc Lond Ser B Biol Sci. 2017;372(1732):20160277.
      Ting CC, Herberman RB. Serological analysis of immune response to friend virus‐induced leukemia. Cancer Res. 1974;34(7):1676‐1683.
      Ting CC. Detection of anti‐tumor antibody in virally induced tumors and its relationship to tumor growth. Int J Cancer. 1976;18(2):205‐215.
      Iwashiro M, Kondo T, Shimizu T, et al. Multiplicity of virus‐encoded helper T‐cell epitopes expressed on FBL‐3 tumor cells. J Virol. 1993;67(8):4533‐4542.
      Shimizu T, Uenishi H, Teramura Y, et al. Fine structure of a virus‐encoded helper T‐cell epitope expressed on FBL‐3 tumor cells. J Virol. 1994;68(12):7704‐7708.
      Eisenthal A, Lafreniere R, Lefor AT, Rosenberg SA. Effect of anti‐B16 melanoma monoclonal antibody on established murine B16 melanoma liver metastases. Cancer Res. 1987;47(11):2771‐2776.
      Leong SP, Muller J, Yetter RA, Gorelik E, Takami T, Hearing VJ. Expression and modulation of a retrovirus‐associated antigen by murine melanoma cells. Cancer Res. 1988;48(17):4954‐4958.
      Li M, Huang X, Zhu Z, Gorelik E. Sequence and insertion sites of murine melanoma‐associated retrovirus. J Virol. 1999;73(11):9178‐9186.
      Kalter SS, Helmke RJ, Heberling RL, et al. Brief communication: C‐type particles in normal human placentas. J Natl Cancer Inst. 1973;50(4):1081‐1084.
      Dirksen ER, Levy JA. Virus‐like particles in placentas from normal individuals and patients with systemic lupus erythematosus. J Natl Cancer Inst. 1977;59(4):1187‐1192.
      Nelson J, Leong JA, Levy JA. Normal human placentas contain RNA‐directed DNA polymerase activity like that in viruses. Proc Natl Acad Sci USA. 1978;75(12):6263‐6267.
      Löwer R, Boller K, Hasenmaier B, et al. Identification of human endogenous retroviruses with complex mRNA expression and particle formation. Proc Natl Acad Sci USA. 1993;90(10):4480‐4484.
      Muster T, Waltenberger A, Grassauer A, et al. An endogenous retrovirus derived from human melanoma cells. Cancer Res. 2003;63(24):8735‐8741.
      Contreras‐Galindo R, Kaplan MH, Leissner P, et al. Human endogenous retrovirus K (HML‐2) elements in the plasma of people with lymphoma and breast cancer. J Virol. 2008;82(19):9329‐9336.
      Contreras‐Galindo R, Kaplan MH, Dube D, et al. Human endogenous retrovirus type K (HERV‐K) particles package and transmit HERV‐K‐related sequences. J Virol. 2015;89(14):7187‐7201.
      Wang‐Johanning F, Rycaj K, Plummer JB, et al. Immunotherapeutic potential of anti‐human endogenous retrovirus‐K envelope protein antibodies in targeting breast tumors. J Natl Cancer Inst. 2012;104(3):189‐210.
      Guo K, Li J, Tang JP, et al. Targeting intracellular oncoproteins with antibody therapy or vaccination. Sci Transl Med. 2011;3(99):99ra85.
      Kudo‐Saito C, Yura M, Yamamoto R, Kawakami Y. Induction of immunoregulatory CD271+ cells by metastatic tumor cells that express human endogenous retrovirus H. Cancer Res. 2014;74(5):1361‐1370.
      Zhou F, Li M, Wei Y, et al. Activation of HERV‐K Env protein is essential for tumorigenesis and metastasis of breast cancer cells. Oncotarget. 2016;7(51):84093‐84117.
      Lemaitre C, Tsang J, Bireau C, Heidmann T, Dewannieux M. A human endogenous retrovirus‐derived gene that can contribute to oncogenesis by activating the ERK pathway and inducing migration and invasion. PLoS Pathog. 2017;13(6):e1006451.
      Li M, Radvanyi L, Yin B, et al. Downregulation of human endogenous retrovirus type K (HERV‐K) viral Env RNA in pancreatic cancer cells decreases cell proliferation and tumor growth. Clin Cancer Res. 2017;23(19):5892‐5911.
      Maze EA, Agit B, Reeves S, et al. Human endogenous retrovirus type K promotes proliferation and confers sensitivity to antiretroviral drugs in Merlin‐negative Schwannoma and meningioma. Cancer Res. 2022;82(2):235‐247.
      Shah AH, Rivas SR, Doucet‐O'Hare TT, et al. Human endogenous retrovirus K contributes to a stem cell niche in glioblastoma. J Clin Invest. 2023;133(13):e167929.
      Panova V, Attig J, Young GR, Stoye JP, Kassiotis G. Antibody‐induced internalisation of retroviral envelope glycoproteins is a signal initiation event. PLoS Pathog. 2020;16(5):e1008605.
      Parikh AR, Szabolcs A, Allen JN, et al. Radiation therapy enhances immunotherapy response in microsatellite stable colorectal and pancreatic adenocarcinoma in a phase II trial. Nat Cancer. 2021;2(11):1124‐1135.
      Heemskerk B, Kvistborg P, Schumacher TN. The cancer antigenome. EMBO J. 2013;32(2):194‐203.
      Isomäki HA, Hakulinen T, Joutsenlahti U. Excess risk of lymphomas, leukemia and myeloma in patients with rheumatoid arthritis. J Chronic Dis. 1978;31(11):691‐696.
      Bernatsky S, Boivin JF, Joseph L, et al. An international cohort study of cancer in systemic lupus erythematosus. Arthritis Rheum. 2005;52(5):1481‐1490.
      Smitten AL, Simon TA, Hochberg MC, Suissa S. A meta‐analysis of the incidence of malignancy in adult patients with rheumatoid arthritis. Arthritis Res Ther. 2008;10(2):R45.
      Parikh‐Patel A, White RH, Allen M, Cress R. Cancer risk in a cohort of patients with systemic lupus erythematosus (SLE) in California. Cancer Causes Control. 2008;19(8):887‐894.
      Mukasa K, Noh JY, Kunii Y, et al. Prevalence of malignant tumors and adenomatous lesions detected by ultrasonographic screening in patients with autoimmune thyroid diseases. Thyroid. 2011;21(1):37‐41.
      Zhou Z, Liu H, Yang Y, et al. The five major autoimmune diseases increase the risk of cancer: epidemiological data from a large‐scale cohort study in China. Cancer Commun (Lond). 2022;42(5):435‐446.
      Moshynska OV, Saxena A. Clonal relationship between Hashimoto thyroiditis and thyroid lymphoma. J Clin Pathol. 2008;61(4):438‐444.
      Bahler DW, Miklos JA, Swerdlow SH. Ongoing Ig gene hypermutation in salivary gland mucosa‐associated lymphoid tissue‐type lymphomas. Blood. 1997;89(9):3335‐3344.
      Pasqualucci L, Neumeister P, Goossens T, et al. Hypermutation of multiple proto‐oncogenes in B‐cell diffuse large‐cell lymphomas. Nature. 2001;412(6844):341‐346.
      Goossens T, Klein U, Küppers R. Frequent occurrence of deletions and duplications during somatic hypermutation: implications for oncogene translocations and heavy chain disease. Proc Natl Acad Sci USA. 1998;95(5):2463‐2468.
      Kleinstern G, Maurer MJ, Liebow M, et al. History of autoimmune conditions and lymphoma prognosis. Blood Cancer J. 2018;8(8):73.
      Wang SS, Vajdic CM, Linet MS, et al. B‐cell NHL subtype risk associated with autoimmune conditions and PRS. Cancer Epidemiol Biomarkers Prev. 2022;31(5):1103‐1110.
      Martins‐Green M, Boudreau N, Bissell MJ. Inflammation is responsible for the development of wound‐induced tumors in chickens infected with Rous sarcoma virus. Cancer Res. 1994;54(16):4334‐4341.
      Ma T, Tang Y, Wang T, et al. Chronic pulmonary bacterial infection facilitates breast cancer lung metastasis by recruiting tumor‐promoting MHCII(hi) neutrophils. Signal Transduct Target Ther. 2023;8(1):296.
      McGee EE, Castro FA, Engels EA, et al. Associations between autoimmune conditions and hepatobiliary cancer risk among elderly US adults. Int J Cancer. 2019;144(4):707‐717.
      Emilsson L, Semrad C, Lebwohl B, Green PHR, Ludvigsson JF. Risk of small bowel adenocarcinoma, adenomas, and carcinoids in a nationwide cohort of individuals with celiac disease. Gastroenterology. 2020;159(5):1686‐1694.e1682.
      He MM, Lo CH, Wang K, et al. Immune‐mediated diseases associated with cancer risks. JAMA Oncol. 2022;8(2):209‐219.
      Shankaran V, Ikeda H, Bruce AT, et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature. 2001;410(6832):1107‐1111.
      Smedby KE, Hjalgrim H, Askling J, et al. Autoimmune and chronic inflammatory disorders and risk of non‐Hodgkin lymphoma by subtype. J Natl Cancer Inst. 2006;98(1):51‐60.
      Pasternak B, Svanström H, Schmiegelow K, Jess T, Hviid A. Use of azathioprine and the risk of cancer in inflammatory bowel disease. Am J Epidemiol. 2013;177(11):1296‐1305.
      Vogrig A, Gigli GL, Segatti S, et al. Epidemiology of paraneoplastic neurological syndromes: a population‐based study. J Neurol. 2020;267(1):26‐35.
      Shah S, Flanagan EP, Paul P, et al. Population‐based epidemiology study of paraneoplastic neurologic syndromes. Neurol Neuroimmunol Neuroinflamm. 2022;9(2):e1124.
      Gozzard P, Woodhall M, Chapman C, et al. Paraneoplastic neurologic disorders in small cell lung carcinoma: a prospective study. Neurology. 2015;85(3):235‐239.
      Corradi JP, Yang C, Darnell JC, Dalmau J, Darnell RB. A post‐transcriptional regulatory mechanism restricts expression of the paraneoplastic cerebellar degeneration antigen cdr2 to immune privileged tissues. J Neurosci. 1997;17(4):1406‐1415.
      Small M, Treilleux I, Couillault C, et al. Genetic alterations and tumor immune attack in Yo paraneoplastic cerebellar degeneration. Acta Neuropathol. 2018;135(4):569‐579.
      Dalmau J, Furneaux HM, Gralla RJ, Kris MG, Posner JB. Detection of the anti‐Hu antibody in the serum of patients with small cell lung cancer—a quantitative western blot analysis. Ann Neurol. 1990;27(5):544‐552.
      Dalmau J, Gultekin SH, Voltz R, et al. Ma1, a novel neuron‐ and testis‐specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders. Brain. 1999;122(Pt 1):27‐39.
      Rosenfeld MR, Eichen JG, Wade DF, Posner JB, Dalmau J. Molecular and clinical diversity in paraneoplastic immunity to Ma proteins. Ann Neurol. 2001;50(3):339‐348.
      Schüller M, Jenne D, Voltz R. The human PNMA family: novel neuronal proteins implicated in paraneoplastic neurological disease. J Neuroimmunol. 2005;169(1–2):172‐176.
      Campillos M, Doerks T, Shah PK, Bork P. Computational characterization of multiple gag‐like human proteins. Trends Genet. 2006;22(11):585‐589.
      Dalmau J, Furneaux HM, Cordon‐Cardo C, Posner JB. The expression of the Hu (paraneoplastic encephalomyelitis/sensory neuronopathy) antigen in human normal and tumor tissues. Am J Pathol. 1992;141(4):881‐886.
      Thibult ML, Mamessier E, Gertner‐Dardenne J, et al. PD‐1 is a novel regulator of human B‐cell activation. Int Immunol. 2013;25(2):129‐137.
      Good‐Jacobson KL, Szumilas CG, Chen L, Sharpe AH, Tomayko MM, Shlomchik MJ. PD‐1 regulates germinal center B cell survival and the formation and affinity of long‐lived plasma cells. Nat Immunol. 2010;11(6):535‐542.
      Kawamoto S, Tran TH, Maruya M, et al. The inhibitory receptor PD‐1 regulates IgA selection and bacterial composition in the gut. Science. 2012;336(6080):485‐489.
      Schonfeld SJ, Tucker MA, Engels EA, et al. Immune‐related adverse events after immune checkpoint inhibitors for melanoma among older adults. JAMA Netw Open. 2022;5(3):e223461.
      Hemminki K, Liu X, Försti A, Ji J, Sundquist J, Sundquist K. Subsequent leukaemia in autoimmune disease patients. Br J Haematol. 2013;161(5):677‐687.
      Hemminki K, Liu X, Ji J, Sundquist J, Sundquist K. Effect of autoimmune diseases on mortality and survival in subsequent digestive tract cancers. Ann Oncol. 2012;23(8):2179‐2184.
      Dedousis D, Vassiliou AN, Cao S, et al. Comparing survival in patients with lung cancer with and without a history of common autoimmune disease. JTO Clin Res Rep. 2022;3(9):100375.
      Dedousis D, Zhang AL, Vassiliou AN, et al. Survival in elderly patients with breast cancer with and without autoimmune disease. Cancer Med. 2023;12(12):13086‐13099.
      Sun R, Breau RH, Mallick R, et al. Prognostic impact of paraneoplastic syndromes on patients with non‐metastatic renal cell carcinoma undergoing surgery: results from Canadian kidney cancer information system. Can Urol Assoc J. 2021;15(4):132‐137.
      Giometto B, Grisold W, Vitaliani R, Graus F, Honnorat J, Bertolini G. Paraneoplastic neurologic syndrome in the PNS Euronetwork database: a European study from 20 centers. Arch Neurol. 2010;67(3):330‐335.
      Maddison P, Gozzard P, Grainge MJ, Lang B. Long‐term survival in paraneoplastic Lambert‐Eaton myasthenic syndrome. Neurology. 2017;88(14):1334‐1339.
      Zitvogel L, Perreault C, Finn OJ, Kroemer G. Beneficial autoimmunity improves cancer prognosis. Nat Rev Clin Oncol. 2021;18(9):591‐602.
      Watson AS, Goutam S, Stukalin I, et al. Association of immune‐related adverse events, hospitalization, and therapy resumption with survival among patients with metastatic melanoma receiving single‐agent or combination immunotherapy. JAMA Netw Open. 2022;5(12):e2245596.
      Cook S, Samuel V, Meyers DE, et al. Immune‐related adverse events and survival among patients with metastatic NSCLC treated with immune checkpoint inhibitors. JAMA Netw Open. 2024;7(1):e2352302.
      Foster CC, Couey MA, Kochanny SE, et al. Immune‐related adverse events are associated with improved response, progression‐free survival, and overall survival for patients with head and neck cancer receiving immune checkpoint inhibitors. Cancer. 2021;127(24):4565‐4573.
      Xing P, Zhang F, Wang G, et al. Incidence rates of immune‐related adverse events and their correlation with response in advanced solid tumours treated with NIVO or NIVO + IPI: a systematic review and meta‐analysis. J Immunother Cancer. 2019;7(1):341.
      Laumont CM, Banville AC, Gilardi M, Hollern DP, Nelson BH. Tumour‐infiltrating B cells: immunological mechanisms, clinical impact and therapeutic opportunities. Nat Rev Cancer. 2022;22(7):414‐430.
      Schumacher TN, Thommen DS. Tertiary lymphoid structures in cancer. Science. 2022;375(6576):eabf9419.
      Pipi E, Nayar S, Gardner DH, Colafrancesco S, Smith C, Barone F. Tertiary lymphoid structures: autoimmunity goes local. Front Immunol. 2018;9:1952.
      Sato Y, Silina K, van den Broek M, Hirahara K, Yanagita M. The roles of tertiary lymphoid structures in chronic diseases. Nat Rev Nephrol. 2023;19(8):525‐537.
      Lavialle C, Cornelis G, Dupressoir A, et al. Paleovirology of ‘syncytins’, retroviral Env genes exapted for a role in placentation. Philos Trans R Soc Lond Ser B Biol Sci. 2013;368(1626):20120507.
      Redelsperger F, Raddi N, Bacquin A, et al. Genetic evidence that captured retroviral envelope syncytins contribute to myoblast fusion and muscle sexual dimorphism in mice. PLoS Genet. 2016;12(9):e1006289.
      Denner J. Endogenous retroviruses expressed in human tumours cannot be used as targets for anti‐tumour vaccines. Transl Oncol. 2021;14(1):100941.
      Prasad M, Lin JL, Gu Y, Gupta R, Macary P, Schwarz H. No crossreactivity of anti‐SARS‐CoV‐2 spike protein antibodies with Syncytin‐1. Cell Mol Immunol. 2021;18(11):2566‐2568.
      Mattar CNZ, Koh W, Seow Y, et al. BNT162B2 COVID‐19 mRNA vaccination did not promote substantial anti‐syncytin‐1 antibody production nor mRNA transfer to breast milk in an exploratory pilot study. Ann Acad Med Singap. 2022;51(5):309‐312.
      Steiner JP, Bachani M, Malik N, et al. Human endogenous retrovirus K envelope in spinal fluid of amyotrophic lateral sclerosis is toxic. Ann Neurol. 2022;92(4):545‐561.
      Liu X, Liu Z, Wu Z, et al. Resurrection of endogenous retroviruses during aging reinforces senescence. Cell. 2022;186(2):287‐304.e26.
      Antony JM, van Marle G, Opii W, et al. Human endogenous retrovirus glycoprotein‐mediated induction of redox reactants causes oligodendrocyte death and demyelination. Nat Neurosci. 2004;7(10):1088‐1095.
      Liu S, Heumüller SE, Hossinger A, et al. Reactivated endogenous retroviruses promote protein aggregate spreading. Nat Commun. 2023;14(1):5034.
    • Grant Information:
      CC2088 United Kingdom WT_ Wellcome Trust; 101018670 International ERC_ European Research Council; CC2088 United Kingdom WT_ Wellcome Trust
    • Contributed Indexing:
      Keywords: autoimmunity; cancer; endogenous retrovirus; envelope glycoprotein; humoral immunity; immunogenicity
    • Accession Number:
      0 (Antibodies, Viral)
      0 (Antigens, Viral)
    • Publication Date:
      Date Created: 20240817 Date Completed: 20241220 Latest Revision: 20241220
    • Publication Date:
      20241220
    • Accession Number:
      10.1111/imr.13378
    • Accession Number:
      39152687