Genes, Antibodies, and Cytokines in Systemic Lupus Erythematosus: Update of Potential Biomarkers

Lina Zaripova 1 * , Abai Baigenzhin 2, Alyona Boltanova 3, Talgat Iglikov 4, Maxim Solomadin 5, Diana Makimova 6, Larissa Kozina 3, Elmira Chuvakova 7
More Detail
1 Department of Scientific and Innovation Management, National Scientific Medical Center, Astana, Kazakhstan
2 Chairman of the Board, National Scientific Medical Center, Astana, Kazakhstan
3 Central Research Laboratory, National Scientific Medical Center, Astana, Kazakhstan
4 Genetic laboratory, National Scientific Medical Center, Astana, Kazakhstan
5 School of Pharmacy, Karaganda Medical University, Karaganda, Kazakhstan
6 Department of Internal Medicine No. 4, Astana Medical University, Astana, Kazakhstan
7 Deputy Chairman of the Board in the field of science, National Scientific Medical Center, Astana, Kazakhstan
* Corresponding Author
J CLIN MED KAZ, Volume 21, Issue 3, pp. 11-19. https://doi.org/10.23950/jcmk/14641
OPEN ACCESS 175 Views 35 Downloads
Download Full Text (PDF)
Author contribution. L.Z. conceived of the presented idea. D.M., M.S., T.I. and Al.B. developed the theory. L.K. and E.Ch. verified the analytical methods. A.B. supervised the findings of this work. All authors discussed the results and contributed to the final manuscript.

ABSTRACT

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown aetiology, with the broad range of antibodies affecting various organs and tissues, leading to rapid disability and even to lethal outcome. Our objective was to make an analysis of the results of relevant global studies about genetic mutations, spectrum of antibodies and cytokines involved in the pathogenesis of SLE. The search was conducted in PubMed and Google Scholar platforms using keywords “systemic lupus erythematosus”, “genetic mutations”, “autoantibodies”, “cytokine production”, “sequencing”, “NGS" and "exome". Several genes were found to be involved in the pathogenesis of SLE, the majority of which were associated with B- and T-cell abnormal activation. The results of different studies revealed an association of active SLE with the increase in specific circulating autoantibodies. Based on the results of the current review, a preliminary list of autoantibodies, genes and cytokines associated with the development of SLE was prepared. Future directions will include the assessment of association of genes, antibodies and cytokines in SLE patients from the local Kazakh population, and the development of genetic-immunologic panel for the early diagnosis of this disease.
Keywords: systemic lupus erythematosus, genes, antibodies, cytokines.

CITATION

Zaripova L, Baigenzhin A, Boltanova A, Iglikov T, Solomadin M, Makimova D, et al. Genes, Antibodies, and Cytokines in Systemic Lupus Erythematosus: Update of Potential Biomarkers. J CLIN MED KAZ. 2024;21(3):11-9. https://doi.org/10.23950/jcmk/14641

REFERENCES

  • Hayter SM, Cook MC. Updated assessment of the prevalence, spectrum and case definition of autoimmune disease. Autoimmunity reviews. 2012;11(10):754-765. https://doi.org/10.1016/j.autrev.2012.02.001.
  • Field MA. Detecting pathogenic variants in autoimmune diseases using high-throughput sequencing. Immunology & Cell Biology. 2021;99(2):146-156. https://doi.org/10.1111/imcb.12372.
  • Wallace B, Vummidi D, Khanna D. Management of connective tissue diseases associated interstitial lung disease: a review of the published literature. Curr Opin Rheumatol. 2016;28(3):236-245. https://doi.org/10.1097/bor.0000000000000270.
  • Rinaldi S, Doria A, Salaffi F, Ermani M, Iaccarino L, Ghirardello A, Zampieri S, Sarzi-Puttini P, Gambari PF, Perini G. Health-related quality of life in Italian patients with systemic lupus erythematosus. I. Relationship between physical and mental dimension and impact of age. Rheumatology (Oxford, England). 2004;43(12):1574-1579. https://doi.org/10.1093/rheumatology/keh397.
  • Olesińska M, Saletra A. Quality of life in systemic lupus erythematosus and its measurement. Reumatologia. 2018;56(1):45-54. https://doi.org/10.5114/reum.2018.74750.
  • Lao C, White D, Rabindranath K, Dantzig PV, Foxall D, Lawrenson R. Mortality and causes of death in systemic lupus erythematosus in New Zealand: a population-based study. Rheumatology. 2023. https://doi.org/10.1093/rheumatology/kead427.
  • Lewis MJ, Jawad AS. The effect of ethnicity and genetic ancestry on the epidemiology, clinical features and outcome of systemic lupus erythematosus. Rheumatology (Oxford, England). 2017;56(suppl_1):i67-i77. https://doi.org/10.1093/rheumatology/kew399.
  • Issayeva B, Aseeva E, Saparbayeva M, Issayeva S, Kulshymanova M, Kaiyrgali SM, Amanzholov A, Bizhanova M, Kalykova M, Solovyev S, et al. Features of clinical manifestations, course, outcomes and health related quality of life in patients with systemic lupus erythematosus in the Republic of Kazakhstan. Rheumatology Science and Practice. 2022;60:602-611. https://doi.org/10.47360/1995-4484-2022-602-611.
  • Isayeva B, Saparbayeva M, Isayeva S, Kulshymanova M, Kaiyrgali SM, Bizhanova M, Nurgaliyev K, Kosherbayeva L, Kulymbetova B, Rysbekova K, et al. The current status of the problem with systemic lupus erythematosus in Kazakhstan. Modern Rheumatology Journal. 2020;14:32-39. https://doi.org/10.14412/1996-7012-2020-1-32-39.
  • Hedrich CM. Shaping the spectrum - From autoinflammation to autoimmunity. Clinical immunology (Orlando, Fla). 2016;165:21-28. https://doi.org/10.1016/j.clim.2016.03.002.
  • Kubota T. An Emerging Role for Anti-DNA Antibodies in Systemic Lupus Erythematosus. Int J Mol Sci. 2023;24(22). https://doi.org/10.3390/ijms242216499.
  • Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey‐Goldman R, Smolen JS, Wofsy D, Boumpas DT, Kamen DL. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Arthritis & rheumatology. 2019;71(9):1400-1412.
  • Menéndez A, Gómez J, Caminal-Montero L, Díaz-López JB, Cabezas-Rodríguez I, Mozo L. Common and specific associations of anti-SSA/Ro60 and anti-Ro52/TRIM21 antibodies in systemic lupus erythematosus. TheScientific World Journal. 2013;2013:832789. https://doi.org/10.1155/2013/832789.
  • Migliorini P, Baldini C, Rocchi V, Bombardieri S. Anti-Sm and anti-RNP antibodies. Autoimmunity. 2005;38(1):47-54. https://doi.org/10.1080/08916930400022715.
  • Trendelenburg M. Autoantibodies against complement component C1q in systemic lupus erythematosus. Clinical & translational immunology. 2021;10(4):e1279. https://doi.org/10.1002/cti2.1279.
  • Stojan G, Petri M. Anti-C1q in systemic lupus erythematosus. Lupus. 2016;25(8):873-877. https://doi.org/10.1177/0961203316645205.
  • Inoue K, Ishizawa M, Kubota T. Monoclonal anti-dsDNA antibody 2C10 escorts DNA to intracellular DNA sensors in normal mononuclear cells and stimulates secretion of multiple cytokines implicated in lupus pathogenesis. Clinical and experimental immunology. 2020;199(2):150-162. https://doi.org/10.1111/cei.13382.
  • Ohl K, Tenbrock K. Inflammatory cytokines in systemic lupus erythematosus. Journal of biomedicine & biotechnology. 2011;2011:432595. https://doi.org/10.1155/2011/432595.
  • Lu R, Munroe ME, Guthridge JM, Bean KM, Fife DA, Chen H, Slight-Webb SR, Keith MP, Harley JB, James JA. Dysregulation of innate and adaptive serum mediators precedes systemic lupus erythematosus classification and improves prognostic accuracy of autoantibodies. Journal of autoimmunity. 2016;74:182-193. https://doi.org/10.1016/j.jaut.2016.06.001.
  • Nepal D, Gazeley D. Role of IL-6 and IL-6 targeted therapy in systemic lupus erythematosus. Rheumatology (Oxford, England). 2023;62(12):3804-3810. https://doi.org/10.1093/rheumatology/kead416.
  • Cunninghame Graham DS, Graham RR, Manku H, Wong AK, Whittaker JC, Gaffney PM, Moser KL, Rioux JD, Altshuler D, Behrens TW, et al. Polymorphism at the TNF superfamily gene TNFSF4 confers susceptibility to systemic lupus erythematosus. Nature genetics. 2008;40(1):83-89. https://doi.org/10.1038/ng.2007.47.
  • Wang YF, Zhang Y, Zhu Z, Wang TY, Morris DL, Shen JJ, Zhang H, Pan HF, Yang J, Yang S, et al. Identification of ST3AGL4, MFHAS1, CSNK2A2 and CD226 as loci associated with systemic lupus erythematosus (SLE) and evaluation of SLE genetics in drug repositioning. Ann Rheum Dis. 2018;77(7):1078-1084. https://doi.org/10.1136/annrheumdis-2018-213093.
  • Díaz-Barreiro A, Bernal-Quirós M, Georg I, Marañón C, Alarcón-Riquelme ME, Castillejo-López C. The SLE variant Ala71Thr of BLK severely decreases protein abundance and binding to BANK1 through impairment of the SH3 domain function. Genes and immunity. 2016;17(2):128-138. https://doi.org/10.1038/gene.2016.1.
  • Ye S, Pang H, Gu YY, Hua J, Chen XG, Bao CD, Wang Y, Zhang W, Qian J, Tsao BP, et al. Protein interaction for an interferon-inducible systemic lupus associated gene, IFIT1. Rheumatology (Oxford, England). 2003;42(10):1155-1163. https://doi.org/10.1093/rheumatology/keg315.
  • Li H, Wang T, Li B, Huang T, Hai Y, Huang C, Xiang W. Bioinformatic analysis of immune-related transcriptome affected by IFIT1 gene in childhood systemic lupus erythematosus. Translational pediatrics. 2023;12(8):1517-1526. 10.21037/tp-23-365.
  • Ranjan S, Panda AK. Association of Toll-Like Receptor 7 (TLR7) Polymorphisms with Predisposition to Systemic Lupus Erythematosus (SLE): A Meta and Trial Sequential Analysis. Biochemical genetics. 2023. https://doi.org/10.1007/s10528-023-10600-9.
  • Fredi M, Bianchi M, Andreoli L, Greco G, Olivieri I, Orcesi S, Fazzi E, Cereda C, Tincani A. Typing TREX1 gene in patients with systemic lupus erythematosus. Reumatismo. 2015;67(1):1-7. https://doi.org/10.4081/reumatismo.2015.782.
  • Zhou D, Rudnicki M, Chua GT, Lawrance SK, Zhou B, Drew JL, Barbar-Smiley F, Armstrong TK, Hilt ME, Birmingham DJ, et al. Human Complement C4B Allotypes and Deficiencies in Selected Cases With Autoimmune Diseases. Front Immunol. 2021;12:739430. https://doi.org/10.3389/fimmu.2021.739430.
  • Kemp ME, Atkinson JP, Skanes VM, Levine RP, Chaplin DD. Deletion of C4A genes in patients with systemic lupus erythematosus. Arthritis and rheumatism. 1987;30(9):1015-1022. https://doi.org/10.1002/art.1780300908.
  • Pereira KMC, Perazzio S, Faria AGA, Moreira ES, Santos VC, Grecco M, da Silva NP, Andrade LEC. Impact of C4, C4A and C4B gene copy number variation in the susceptibility, phenotype and progression of systemic lupus erythematosus. Advances in Rheumatology. 2019;59(1):36. https://doi.org/10.1186/s42358-019-0076-6.
  • Tsai LJ, Hsiao SH, Tsai LM, Lin CY, Tsai JJ, Liou DM, Lan JL. The sodium-dependent glucose cotransporter SLC5A11 as an autoimmune modifier gene in SLE. Tissue antigens. 2008;71(2):114-126. https://doi.org/10.1111/j.1399-0039.2007.00975.x.
  • Li Y, Ma C, Liao S, Qi S, Meng S, Cai W, Dai W, Cao R, Dong X, Krämer BK, et al. Combined proteomics and single cell RNA-sequencing analysis to identify biomarkers of disease diagnosis and disease exacerbation for systemic lupus erythematosus. Front Immunol. 2022;13:969509. https://doi.org/10.3389/fimmu.2022.969509.
  • Jiang SH, Athanasopoulos V, Ellyard JI, Chuah A, Cappello J, Cook A, Prabhu SB, Cardenas J, Gu J, Stanley M, et al. Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus. Nature communications. 2019;10(1):2201. https://doi.org/10.1038/s41467-019-10242-9.
  • Zheng F, Xu H, Zhang C, Hong X, Liu D, Tang D, Xiong Z, Dai Y. Immune cell and TCR/BCR repertoire profiling in systemic lupus erythematosus patients by single-cell sequencing. Aging. 2021;13(21):24432-24448. https://doi.org/10.18632/aging.203695.
  • Simpfendorfer KR, Olsson LM, Manjarrez Orduño N, Khalili H, Simeone AM, Katz MS, Lee AT, Diamond B, Gregersen PK. The autoimmunity-associated BLK haplotype exhibits cis-regulatory effects on mRNA and protein expression that are prominently observed in B cells early in development. Human molecular genetics. 2012;21(17):3918-3925. https://doi.org/10.1093/hmg/dds220.
  • Soto L, Ferrier A, Aravena O, Fonseca E, Berendsen J, Biere A, Bueno D, Ramos V, Aguillón JC, Catalán D. Systemic Sclerosis Patients Present Alterations in the Expression of Molecules Involved in B-Cell Regulation. Front Immunol. 2015;6:496. https://doi.org/10.3389/fimmu.2015.00496.
  • Flores-Borja F, Jury EC, Mauri C, Ehrenstein MR. Defects in CTLA-4 are associated with abnormal regulatory T cell function in rheumatoid arthritis. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(49):19396-19401. https://doi.org/10.1073/pnas.0806855105.
  • Lee JH, Kim B, Jin WJ, Kim HH, Ha H, Lee ZH. Pathogenic roles of CXCL10 signaling through CXCR3 and TLR4 in macrophages and T cells: relevance for arthritis. Arthritis Res Ther. 2017;19(1):163. https://doi.org/10.1186/s13075-017-1353-6.
  • Mohammadoo-Khorasani M, Salimi S, Tabatabai E, Sandoughi M, Zakeri Z, Farajian-Mashhadi F. Interleukin-1β (IL-1β) & IL-4 gene polymorphisms in patients with systemic lupus erythematosus (SLE) & their association with susceptibility to SLE. The Indian journal of medical research. 2016;143(5):591-596. https://doi.org/10.4103/0971-5916.187107.
  • Shen M, Duan C, Xie C, Wang H, Li Z, Li B, Wang T. Identification of key interferon-stimulated genes for indicating the condition of patients with systemic lupus erythematosus. Front Immunol. 2022;13:962393. https://doi.org/10.3389/fimmu.2022.962393.
  • Shao WH, Cohen PL. The role of tyrosine kinases in systemic lupus erythematosus and their potential as therapeutic targets. Expert Rev Clin Immunol. 2014;10(5):573-582. https://doi.org/10.1586/1744666x.2014.893827.
  • Bakutenko IY, Haurylchyk ID, Nikitchenko NV, Sechko EV, Kozyro IA, Tchitchko AM, Batyan GM, Sukalo AV, Ryabokon NI. Neutrophil cytosolic factor 2 (NCF2) gene polymorphism is associated with juvenile-onset systemic lupus erythematosus, but probably not with other autoimmune rheumatic diseases in children. Molecular genetics & genomic medicine. 2022;10(1):e1859. https://doi.org/10.1002/mgg3.1859.
  • Chua KH, Lian LH, Sim XJ, Cheah TE, Lau TP. Association between PDCD1 Gene Polymorphisms and Risk of Systemic Lupus Erythematosus in Three Main Ethnic Groups of the Malaysian Population. Int J Mol Sci. 2015;16(5):9794-9803. https://doi.org/10.3390/ijms16059794.
  • Román-Fernández IV, Machado-Contreras JR, Muñoz-Valle JF, Cruz A, Salazar-Camarena DC, Palafox-Sánchez CA. Altered PTPN22 and IL10 mRNA Expression Is Associated with Disease Activity and Renal Involvement in Systemic Lupus Erythematosus. Diagnostics (Basel, Switzerland). 2022;12(11). https://doi.org/10.3390/diagnostics12112859.
  • Molineros JE, Singh B, Terao C, Okada Y, Kaplan J, McDaniel B, Akizuki S, Sun C, Webb CF, Looger LL, et al. Mechanistic Characterization of RASGRP1 Variants Identifies an hnRNP-K-Regulated Transcriptional Enhancer Contributing to SLE Susceptibility. Front Immunol. 2019;10:1066. https://doi.org/10.3389/fimmu.2019.01066.
  • Lanata CM, Paranjpe I, Nititham J, Taylor KE, Gianfrancesco M, Paranjpe M, Andrews S, Chung SA, Rhead B, Barcellos LF, et al. A phenotypic and genomics approach in a multi-ethnic cohort to subtype systemic lupus erythematosus. Nature communications. 2019;10(1):3902. https://doi.org/10.1038/s41467-019-11845-y.
  • Goropevšek A, Holcar M, Avčin T. The Role of STAT Signaling Pathways in the Pathogenesis of Systemic Lupus Erythematosus. Clinical reviews in allergy & immunology. 2017;52(2):164-181. https://doi.org/10.1007/s12016-016-8550-y.
  • Petrackova A, Horak P, Radvansky M, Skacelova M, Fillerova R, Kudelka M, Smrzova A, Mrazek F, Kriegova E. Cross-Disease Innate Gene Signature: Emerging Diversity and Abundance in RA Comparing to SLE and SSc. Journal of immunology research. 2019;2019:3575803. https://doi.org/10.1155/2019/3575803.
  • Kim T, Bae SC, Kang C. Synergistic activation of NF-κB by TNFAIP3 (A20) reduction and UBE2L3 (UBCH7) augment that synergistically elevate lupus risk. Arthritis Res Ther. 2020;22(1):93. https://doi.org/10.1186/s13075-020-02181-4.
  • Brown GJ, Cañete PF, Wang H, Medhavy A, Bones J, Roco JA, He Y, Qin Y, Cappello J, Ellyard JI, et al. TLR7 gain-of-function genetic variation causes human lupus. Nature. 2022;605(7909):349-356. https://doi.org/10.1038/s41586-022-04642-z.
  • Fang L, Ying S, Xu X, Wu D. TREX1 cytosolic DNA degradation correlates with autoimmune disease and cancer immunity. Clinical and experimental immunology. 2023;211(3):193-207. https://doi.org/10.1093/cei/uxad017.
  • Lundtoft C, Pucholt P, Martin M, Bianchi M, Lundström E, Eloranta ML, Sandling JK, Sjöwall C, Jönsen A, Gunnarsson I, et al. Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases. Arthritis & rheumatology (Hoboken, NJ). 2022;74(8):1440-1450. https://doi.org/10.1002/art.42122.
  • Chen K, Li X, Shang Y, Chen D, Qu S, Shu J, Zhang M, Wang Z, Huang J, Wu M, et al. FGL1-LAG3 axis impairs IL-10-Producing regulatory T cells associated with Systemic lupus erythematosus disease activity. Heliyon. 2023;9(10):e20806. https://doi.org/10.1016/j.heliyon.2023.e20806.
  • Cohen PL, Shao WH. Gas6/TAM Receptors in Systemic Lupus Erythematosus. Disease markers. 2019;2019:7838195. 10.1155/2019/7838195.
  • Liu M, Wu W, Sun X, Yang J, Xu J, Fu W, Li M. New insights into CD4(+) T cell abnormalities in systemic sclerosis. Cytokine Growth Factor Rev. 2016;28:31-36. https://doi.org/10.1016/j.cytogfr.2015.12.002.
  • Greisen SR, Schelde KK, Rasmussen TK, Kragstrup TW, Stengaard-Pedersen K, Hetland ML, Hørslev-Petersen K, Junker P, Østergaard M, Deleuran B, et al. CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic 'window of opportunity'. Arthritis Res Ther. 2014;16(5):434. https://doi.org/10.1186/s13075-014-0434-z.
  • Favilli F, Anzilotti C, Martinelli L, Quattroni P, De Martino S, Pratesi F, Neumann D, Beermann S, Novick D, Dinarello CA, et al. IL-18 activity in systemic lupus erythematosus. Annals of the New York Academy of Sciences. 2009;1173:301-309. https://doi.org/10.1111/j.1749-6632.2009.04742.x.
  • Winkler A, Sun W, De S, Jiao A, Sharif MN, Symanowicz PT, Athale S, Shin JH, Wang J, Jacobson BA, et al. The Interleukin-1 Receptor-Associated Kinase 4 Inhibitor PF-06650833 Blocks Inflammation in Preclinical Models of Rheumatic Disease and in Humans Enrolled in a Randomized Clinical Trial. Arthritis & rheumatology (Hoboken, NJ). 2021;73(12):2206-2218. https://doi.org/10.1002/art.41953.
  • Lang T, Foote A, Lee JP, Morand EF, Harris J. MIF: Implications in the Pathoetiology of Systemic Lupus Erythematosus. Front Immunol. 2015;6:577. https://doi.org/10.3389/fimmu.2015.00577.
  • Huijser E, van Helden-Meeuwsen CG, Groot N, Bodewes ILA, Wahadat MJ, Schreurs MWJ, van Daele PLA, Dalm V, van Laar JAM, van Hagen PM, et al. MxA is a clinically applicable biomarker for type I interferon activation in systemic lupus erythematosus and systemic sclerosis. Rheumatology (Oxford, England). 2019;58(7):1302-1303. https://doi.org/10.1093/rheumatology/kez078.
  • Remmers EF, Sano H, Lafyatis R, Case JP, Kumkumian GK, Hla T, Maciag T, Wilder RL. Production of platelet derived growth factor B chain (PDGF-B/c-sis) mRNA and immunoreactive PDGF B-like polypeptide by rheumatoid synovium: coexpression with heparin binding acidic fibroblast growth factor-1. The Journal of rheumatology. 1991;18(1):7-13.
  • Baroja-Mazo A, Pelegrín P. Modulating P2X7 Receptor Signaling during Rheumatoid Arthritis: New Therapeutic Approaches for Bisphosphonates. Journal of osteoporosis. 2012;2012:408242. https://doi.org/10.1155/2012/408242.
  • Juárez-Vicuña Y, Pérez-Ramos J, Adalid-Peralta L, Sánchez F, Martínez-Martínez LA, Ortiz-Segura MDC, Pichardo-Ontiveros E, Hernández-Díazcouder A, Amezcua-Guerra LM, Ramírez-Bello J, et al. Interferon Lambda 3/4 (IFNλ3/4) rs12979860 Polymorphisms Is Not Associated With Susceptibility to Systemic Lupus Erythematosus, Although It Regulates OASL Expression in Patients With SLE. Frontiers in genetics. 2021;12:647487. https://doi.org/10.3389/fgene.2021.647487.
  • Tang J, Gu Y, Zhang M, Ye S, Chen X, Guo Q, Qian J, Bao C, Chen S, Shen N. Increased expression of the type I interferon-inducible gene, lymphocyte antigen 6 complex locus E, in peripheral blood cells is predictive of lupus activity in a large cohort of Chinese lupus patients. Lupus. 2008;17(9):805-813. https://doi.org/10.1177/0961203308089694.
  • Carter V, LaCava J, Taylor MS, Liang SY, Mustelin C, Ukadike KC, Bengtsson A, Lood C, Mustelin T. High Prevalence and Disease Correlation of Autoantibodies Against p40 Encoded by Long Interspersed Nuclear Elements in Systemic Lupus Erythematosus. Arthritis & rheumatology (Hoboken, NJ). 2020;72(1):89-99. https://doi.org/10.1002/art.41054.
  • Geneva-Popova MG, Popova-Belova SD, Gardzheva PN, Kraev KI. A Study of IFN-α-Induced Chemokines CCL2, CXCL10 and CCL19 in Patients with Systemic Lupus Erythematosu. Life (Basel, Switzerland). 2022;12(2). https://doi.org/10.3390/life12020251.
  • Iwamoto T, Niewold TB. Genetics of human lupus nephritis. Clinical immunology (Orlando, Fla). 2017;185:32-39. https://doi.org/10.1016/j.clim.2016.09.012.
  • Conrad N, Misra S, Verbakel JY, Verbeke G, Molenberghs G, Taylor PN, Mason J, Sattar N, McMurray JJV, McInnes IB, et al. Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK. Lancet (London, England). 2023;401(10391):1878-1890. https://doi.org/10.1016/s0140-6736(23)00457-9.
  • Ahmed SS, Lambert P-H. Chapter 20 - Autoimmune Diseases: The Role for Vaccines. In: Rose NR, Mackay IR, editors. The Autoimmune Diseases (Fifth Edition). Boston: Academic Press; 2014. p. 275-282.
  • Surace AEA, Hedrich CM. The Role of Epigenetics in Autoimmune/Inflammatory Disease. Front Immunol. 2019;10:1525. https://doi.org/10.3389/fimmu.2019.01525.
  • Ulff-Møller CJ, Asmar F, Liu Y, Svendsen AJ, Busato F, Grønbaek K, Tost J, Jacobsen S. Twin DNA Methylation Profiling Reveals Flare-Dependent Interferon Signature and B Cell Promoter Hypermethylation in Systemic Lupus Erythematosus. Arthritis & rheumatology (Hoboken, NJ). 2018;70(6):878-890. https://doi.org/10.1002/art.40422.
  • Deapen D, Escalante A, Weinrib L, Horwitz D, Bachman B, Roy-Burman P, Walker A, Mack TM. A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis and rheumatism. 1992;35(3):311-318. https://doi.org/10.1002/art.1780350310.
  • Zervou MI, Andreou A, Matalliotakis M, Spandidos DA, Goulielmos GN, Eliopoulos EE. Association of the DNASE1L3 rs35677470 polymorphism with systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis: Structural biological insights. Molecular Medicine Reports. 2020;22(6):4492-4498.
  • Belot A, Rice G, Omarjee S, Rouchon Q, Smith E, Moreews M, Tusseau M, Frachette C, Bournhonesque R, Thielens N, et al. Contribution of rare and predicted pathogenic gene variants to childhood-onset lupus: a large, genetic panel analysis of British and French cohorts. The Lancet Rheumatology. 2020;2. https://doi.org/10.1016/S2665-9913(19)30142-0.
  • Balow JE, Jr., Ryan JG, Chae JJ, Booty MG, Bulua A, Stone D, Sun HW, Greene J, Barham B, Goldbach-Mansky R, et al. Microarray-based gene expression profiling in patients with cryopyrin-associated periodic syndromes defines a disease-related signature and IL-1-responsive transcripts. Ann Rheum Dis. 2013;72(6):1064-1070. https://doi.org/10.1136/annrheumdis-2012-202082.
  • Hedrich CM, Tsokos GC. Epigenetic mechanisms in systemic lupus erythematosus and other autoimmune diseases. Trends in molecular medicine. 2011;17(12):714-724. https://doi.org/10.1016/j.molmed.2011.07.005.
  • Goulielmos GN, Zervou MI, Vazgiourakis VM, Ghodke-Puranik Y, Garyfallos A, Niewold TB. The genetics and molecular pathogenesis of systemic lupus erythematosus (SLE) in populations of different ancestry. Gene. 2018;668:59-72. https://doi.org/10.1016/j.gene.2018.05.041.
  • Sestan M, Kifer N, Arsov T, Cook M, Ellyard J, Vinuesa CG, Jelusic M. The Role of Genetic Risk Factors in Pathogenesis of Childhood-Onset Systemic Lupus Erythematosus. Current issues in molecular biology. 2023;45(7):5981-6002.
  • Cho JH, Feldman M. Heterogeneity of autoimmune diseases: pathophysiologic insights from genetics and implications for new therapies. Nature medicine. 2015;21(7):730-738. https://doi.org/10.1038/nm.3897.