State of the Art REVIEW
61 Grimaldi CM, Cleary J, Dagtas AS, Moussai D, Diamond B. Estrogen alters thresholds for B cell apoptosis and activation. J Clin Invest 2002;109:1625-33. doi:10.1172/JCI0214873. 62 Grimaldi CM, Jeganathan V, Diamond B. Hormonal regulation of B cell development: 17 beta-estradiol impairs negative selection of high-affinity DNA-reactive B cells at more than one developmental checkpoint. J Immunol 2006;176:2703-10. doi:10.4049/ jimmunol.176.5.2703. 63 Jeganathan V, Peeva E, Diamond B. Hormonal milieu at time of B cell activation controls duration of autoantibody response. J Autoimmun 2014;53:46-54. doi:10.1016/j.jaut.2014.02.007. 64 Panchanathan R, Choubey D. Murine BAFF expression is up- regulated by estrogen and interferons: implications for sex bias in the development of autoimmunity. Mol Immunol 2013;53:15-23. doi:10.1016/j.molimm.2012.06.013. 65 Singh RP, Hahn BH, Bischoff DS. Interferon genes are influenced by 17beta-estradiol in SLE. Front Immunol 2021;12:725325. doi:10.3389/fimmu.2021.725325. 66 Kovats S. Estrogen receptors regulate innate immune cells and signaling pathways. Cell Immunol 2015;294:63-9. doi:10.1016/j. cellimm.2015.01.018. 67 Wu Z, Sun Y, Mei X, Zhang C, Pan W, Shi W. 17β-oestradiol enhances global DNA hypomethylation in CD4-positive T cells from female patients with lupus, through overexpression of oestrogen receptor-α-mediated downregulation of DNMT1. Clin Exp Dermatol 2014;39:525-32. doi:10.1111/ced.12346. 68 Dragin N, Bismuth J, Cizeron-Clairac G, et al. Estrogen-mediated downregulation of AIRE influences sexual dimorphism in autoimmune diseases. J Clin Invest 2016;126:1525-37. doi:10.1172/JCI81894. 69 Khan D, Dai R, Ansar Ahmed S. Sex differences and estrogen regulation of miRNAs in lupus, a prototypical autoimmune disease. Cell Immunol 2015;294:70-9. doi:10.1016/j.cellimm.2015.01.004. 70 Petri M, Kim MY, Kalunian KC, et al, OC-SELENA Trial. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med 2005;353:2550-8. doi:10.1056/NEJMoa051135 71 Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 2012;13:484-92. doi:10.1038/ nrg3230. 72 Lanata CM, Blazer A, Criswell LA. The contribution of genetics and epigenetics to our understanding of health disparities in rheumatic diseases. Rheum Dis Clin North Am 2021;47:65-81. doi:10.1016/j. rdc.2020.09.005. 73 Coit P, Jeffries M, Altorok N, et al. Genome-wide DNA methylation study suggests epigenetic accessibility and transcriptional poising of interferon-regulated genes in naïve CD4+ T cells from lupus patients. J Autoimmun 2013;43:78-84. doi:10.1016/j.jaut.2013.04.003. 74 Lanata CM, Paranjpe I, Nititham J, et al. A phenotypic and genomics approach in a multi-ethnic cohort to subtype systemic lupus erythematosus. Nat Commun 2019;10:3902. doi:10.1038/s41467- 019-11845-y. 75 Baechler EC, Batliwalla FM, Karypis G, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A 2003;100:2610-5. doi:10.1073/ pnas.0337679100 76 Northcott M, Jones S, Koelmeyer R, et al. Type 1 interferon status in systemic lupus erythematosus: a longitudinal analysis. Lupus Sci Med 2022;9:e000625. doi:10.1136/lupus-2021-000625. 77 Lanata CM, Nititham J, Taylor KE, et al. The dynamics of methylation of CpG sites associated with SLE subtypes in a longitudinal cohort. Arthritis Rheumatol 2022;74:1676-86. doi:10.1002/art.42237 78 Dinse GE, Parks CG, Weinberg CR, et al. Antinuclear antibodies and mortality in the National Health and Nutrition Examination Survey (1999-2004). PLoS One 2017;12:e0185977. doi:10.1371/journal. pone.0185977. 79 Solow EB, Vongpatanasin W, Skaug B, Karp DR, Ayers C, de Lemos JA. Antinuclear antibodies are associated with all-cause mortality and cardiovascular outcomes in the general population. J Am Coll Cardiol 2015;65:2669-70. doi:10.1016/j.jacc.2015.03.578. 80 Lövgren T, Eloranta ML, Båve U, Alm GV, Rönnblom L. Induction of interferon-alpha production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG. Arthritis Rheum 2004;50:1861- 72. doi:10.1002/art.20254 81 Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003;349:1526-33. doi:10.1056/ NEJMoa021933 82 Munroe ME, Lu R, Zhao YD, et al. Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification. Ann Rheum Dis 2016;75:2014-21. doi:10.1136/annrheumdis-2015-208140. 83 Sterner RM, Hartono SP, Grande JP. The pathogenesis of lupus nephritis. J Clin Cell Immunol 2014;5:205. doi:10.4172/2155- 9899.1000205.
that other autoimmune disorders variably share. Hum Mol Genet 2015;24:582-96. doi:10.1093/hmg/ddu455. 38 Sankararaman S, Mallick S, Dannemann M, et al. The genomic landscape of Neanderthal ancestry in present-day humans. Nature 2014;507:354-7. doi:10.1038/nature12961. 39 Scofield RH, Bruner GR, Namjou B, et al. Klinefelter’s syndrome (47,XXY) in male systemic lupus erythematosus patients: support for the notion of a gene-dose effect from the X chromosome. Arthritis Rheum 2008;58:2511-7. doi:10.1002/art.23701. 40 Liu K, Kurien BT, Zimmerman SL, et al. X chromosome dose and sex bias in autoimmune diseases: increased prevalence of 47,XXX in systemic lupus erythematosus and Sjögren’s syndrome. Arthritis Rheumatol 2016;68:1290-300. doi:10.1002/art.39560. 41 Fang H, Disteche CM, Berletch JB. X inactivation and escape: epigenetic and structural features. Front Cell Dev Biol 2019;7:219. doi:10.3389/fcell.2019.00219. 42 Carrel L, Willard HF. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 2005;434:400-4. doi:10.1038/nature03479. 43 Hagen SH, Henseling F, Hennesen J, et al. heterogeneous escape from X chromosome inactivation results in sex differences in type I IFN responses at the single human pDC level. Cell Rep 2020;33:108485. doi:10.1016/j.celrep.2020.108485. 44 Souyris M, Cenac C, Azar P, et al. TLR7 escapes X chromosome inactivation in immune cells. Sci Immunol 2018;3:eaap8855. doi:10.1126/sciimmunol.aap8855. 45 Wang J, Syrett CM, Kramer MC, Basu A, Atchison ML, Anguera MC. Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X. Proc Natl Acad Sci U S A 2016;113:E2029-38. doi:10.1073/ pnas.1520113113. 46 Jiwrajka N, Anguera MC. The X in seX-biased immunity and autoimmune rheumatic disease. J Exp Med 2022;219:e20211487. doi:10.1084/jem.20211487. 47 Lu Q, Wu A, Tesmer L, Ray D, Yousif N, Richardson B. Demethylation of CD40LG on the inactive X in T cells from women with lupus. J Immunol 2007;179:6352-8. doi:10.4049/jimmunol.179.9.6352. 48 Hewagama A, Gorelik G, Patel D, et al, Michigan Lupus Cohort. Overexpression of X-linked genes in T cells from women with lupus. J Autoimmun 2013;41:60-71. doi:10.1016/j.jaut.2012.12.006. 49 Pyfrom S, Paneru B, Knox JJ, et al. The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients. Proc Natl Acad Sci U S A 2021;118:e2024624118. doi:10.1073/pnas.2024624118. 50 Ngo D, Cheng Q, O’Connor AE, et al. Glucocorticoid-induced leucine zipper (GILZ) regulates testicular FOXO1 activity and spermatogonial stem cell (SSC) function. PLoS One 2013;8:e59149. doi:10.1371/ journal.pone.0059149 51 Jones SA, Toh AE, Odobasic D, et al. Glucocorticoid-induced leucine zipper (GILZ) inhibits B cell activation in systemic lupus erythematosus. Ann Rheum Dis 2016;75:739-47. doi:10.1136/ annrheumdis-2015-207744. 52 Jones SA, Perera DN, Fan H, Russ BE, Harris J, Morand EF. GILZ regulates Th17 responses and restrains IL-17-mediated skin inflammation. J Autoimmun 2015;61:73-80. doi:10.1016/j. jaut.2015.05.010. 53 Nataraja C, Dankers W, Flynn J, et al. GILZ Regulates the expression of pro-inflammatory cytokines and protects against end-organ damage in a model of lupus. Front Immunol 2021;12:652800. doi:10.3389/ fimmu.2021.652800. 54 Nataraja C, Flynn J, Dankers W, et al. GILZ regulates type I interferon release and sequesters STAT1. J Autoimmun 2022;131:102858. doi:10.1016/j.jaut.2022.102858. 55 Rojas-Villarraga A, Torres-Gonzalez JV, Ruiz-Sternberg Á-M. Safety of hormonal replacement therapy and oral contraceptives in systemic lupus erythematosus: a systematic review and meta-analysis. PLoS One 2014;9:e104303. doi:10.1371/journal.pone.0104303. 56 Eudy AM, Siega-Riz AM, Engel SM, et al. Effect of pregnancy on disease flares in patients with systemic lupus erythematosus. Ann Rheum Dis 2018;77:855-60. doi:10.1136/ annrheumdis-2017-212535. 57 Roubinian JR, Talal N, Greenspan JS, Goodman JR, Siiteri PK. Effect of castration and sex hormone treatment on survival, anti-nucleic acid antibodies, and glomerulonephritis in NZB/NZW F1 mice. J Exp Med 1978;147:1568-83. doi:10.1084/jem.147.6.1568. 58 Bynoté KK, Hackenberg JM, Korach KS, Lubahn DB, Lane PH, Gould KA. Estrogen receptor-alpha deficiency attenuates autoimmune disease in (NZB x NZW)F1 mice. Genes Immun 2008;9:137-52. doi:10.1038/sj.gene.6364458. 59 Cutolo M, Straub RH. Sex steroids and autoimmune rheumatic diseases: state of the art. Nat Rev Rheumatol 2020;16:628-44. doi:10.1038/s41584-020-0503-4. 60 Bynoe MS, Grimaldi CM, Diamond B. Estrogen up-regulates Bcl-2 and blocks tolerance induction of naive B cells. Proc Natl Acad Sci U S A 2000;97:2703-8. doi:10.1073/pnas.040577497.
16
doi: 10.1136/bmj-2022-073980 | BMJ 2023;383:073980 | the bmj
Powered by FlippingBook