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Review

Sex and autoimmunity: proposed mechanisms of disease onset and severity

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Pages 607-615 | Received 27 Oct 2018, Accepted 09 Apr 2019, Published online: 29 Apr 2019

References

  • Moving toward precision medicine. Lancet. 2011; 378:1678.
  • Selmi C. Autoimmunity in 2017. Clin Rev Allergy Immunol. 2018.
  • Sirotti S, Generali E, Ceribelli A, et al. Personalized medicine in rheumatology: the paradigm of serum autoantibodies. Auto Immun Highlights. 2017;8:10.
  • Selmi C, Ceribelli A, Generali E, et al. Serum antinuclear and extractable nuclear antigen antibody prevalence and associated morbidity and mortality in the general population over 15 years. Autoimmun Rev. 2016;15:162–166.
  • Ma WT, Chang C, Gershwin ME, et al. Development of autoantibodies precedes clinical manifestations of autoimmune diseases: A comprehensive review. J Autoimmun. 2017;83:95–112.
  • McCombe PA, Greer JM, Mackay IR. Sexual dimorphism in autoimmune disease. Curr Mol Med. 2009;9:1058–1079.
  • Favalli EG, Biggioggero M, Crotti C, et al. Sex and management of rheumatoid arthritis. Clin Rev Allergy Immunol. 2018.
  • Chua-Aguilera CJ, Moller B, Yawalkar N. Skin manifestations of rheumatoid arthritis, juvenile idiopathic arthritis, and spondyloarthritides. Clin Rev Allergy Immunol. 2017;53:371–393.
  • Ribero S, Sciascia S, Borradori L, et al. The cutaneous spectrum of lupus erythematosus. Clin Rev Allergy Immunol. 2017;53:291–305.
  • Sanz Perez I, Martinez Valle F, Guillen-Del-Castillo A, et al. Subclinical cardiovascular disease and systemic sclerosis: a comparison between risk charts, quantification of coronary calcium and carotid ultrasonography. Autoimmun Rev. 2018;17:900–905.
  • De Carolis S, Tabacco S, Rizzo F, et al. Antiphospholipid syndrome: an update on risk factors for pregnancy outcome. Autoimmun Rev. 2018;17:956–966.
  • Paule R, Morel N, Le Guern V, et al. Classification of primary antiphospholipid syndrome as systemic lupus erythematosus: analysis of a cohort of 214 patients. Autoimmun Rev. 2018;17:866–872.
  • Mainetti C, Terziroli Beretta-Piccoli B, Selmi C. Cutaneous manifestations of dermatomyositis: a comprehensive review. Clin Rev Allergy Immunol. 2017;53:337–356.
  • Anaya JM, Restrepo-Jimenez P, Rodriguez Y, et al. Sjogren‘s syndrome and autoimmune thyroid disease: two sides of the same coin. Clin Rev Allergy Immunol. 2018.
  • Generali E, Costanzo A, Mainetti C, et al. Cutaneous and mucosal manifestations of sjogren‘s syndrome. Clin Rev Allergy Immunol. 2017;53:357–370.
  • Psianou K, Panagoulias I, Papanastasiou AD, et al. Clinical and immunological parameters of Sjogren‘s syndrome. Autoimmun Rev. 2018;17:1053–1064.
  • Berteau F, Rouviere B, Delluc A, et al. Autosomic dominant familial Behcet disease and haploinsufficiency A20: A review of the literature. Autoimmun Rev. 2018;17:809–815.
  • Voskuhl RR, Gold SM. Sex-related factors in multiple sclerosis susceptibility and progression. Nat Rev Neurol. 2012;8:255–263.
  • Libert C, Dejager L, Pinheiro I. The X chromosome in immune functions: when a chromosome makes the difference. Nat Rev Immunol. 2010;10:594–604.
  • Selmi C, Brunetta E, Raimondo MG, et al. The X chromosome and the sex ratio of autoimmunity. Autoimmun Rev. 2012;11:A531–7.
  • Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16:626–638.
  • Seminog OO, Seminog AB, Yeates D, et al. Associations between Klinefelter‘s syndrome and autoimmune diseases: english national record linkage studies. Autoimmunity. 2015;48:125–128.
  • Bianchi I, Lleo A, Gershwin ME, et al. The X chromosome and immune associated genes. J Autoimmun. 2012;38:J187–92.
  • Smith-Bouvier DL, Divekar AA, Sasidhar M, et al. A role for sex chromosome complement in the female bias in autoimmune disease. J Exp Med. 2008;205:1099–1108.
  • Webb GJ, Siminovitch KA, Hirschfield GM. The immunogenetics of primary biliary cirrhosis: A comprehensive review. J Autoimmun. 2015;64:42–52.
  • Hsueh YH, Chen HW, Syu BJ, et al. Endogenous IL-10 maintains immune tolerance but IL-10 gene transfer exacerbates autoimmune cholangitis. J Autoimmun. 2018 Dec;95:159–170.
  • Ratliff ML, Garton J, Garman L, et al. ARID3a gene profiles are strongly associated with human interferon alpha production. J Autoimmun. 2019 Jan;96:158–167.
  • Bae HR, Leung PS, Tsuneyama K, et al. Chronic expression of interferon-gamma leads to murine autoimmune cholangitis with a female predominance. Hepatology. 2016;64:1189–1201.
  • Bae HR, Hodge DL, Yang GX, et al. The interplay of type I and type II interferons in murine autoimmune cholangitis as a basis for sex-biased autoimmunity. Hepatology. 2018;67:1408–1419.
  • Svendsen AJ, Tan Q, Jakobsen MA, et al. White blood cell mitochondrial DNA copy number is decreased in rheumatoid arthritis and linked with risk factors. A twin study. J Autoimmun. 2019 Jan;96:142–146.
  • Lleo A, Zhang W, Zhao M, et al. DNA methylation profiling of the X chromosome reveals an aberrant demethylation on CXCR3 promoter in primary biliary cirrhosis. Clin Epigenetics. 2015;7:61.
  • Lleo A, Oertelt-Prigione S, Bianchi I, et al. Y chromosome loss in male patients with primary biliary cirrhosis. J Autoimmun. 2013;41:87–91.
  • Invernizzi P, Miozzo M, Battezzati PM, et al. Frequency of monosomy X in women with primary biliary cirrhosis. Lancet. 2004;363:533–535.
  • Invernizzi P, Miozzo M, Selmi C, et al. X chromosome monosomy: a common mechanism for autoimmune diseases. J Immunol. 2005;175:575–578.
  • Terziroli Beretta-Piccoli B, Stirnimann G, Cerny A, et al. Geoepidemiology of primary biliary cholangitis: lessons from Switzerland. Clin Rev Allergy Immunol. 2018;54:295–306.
  • Joseph S, George NI, Green-Knox B, et al. Epigenome-wide association study of peripheral blood mononuclear cells in systemic lupus erythematosus: identifying DNA methylation signatures associated with interferon-related genes based on ethnicity and SLEDAI. J Autoimmun. 2019 Jan;96:147–157.
  • Selmi C, Leung PS, Sherr DH, et al. Mechanisms of environmental influence on human autoimmunity: a National Institute of Environmental Health Sciences expert panel workshop. J Autoimmun. 2012;39:272–284.
  • Selmi C, Feghali-Bostwick CA, Lleo A, et al. X chromosome gene methylation in peripheral lymphocytes from monozygotic twins discordant for scleroderma. Clin Exp Immunol. 2012;169:253–262.
  • Generali E, Ceribelli A, Stazi MA, et al. Lessons learned from twins in autoimmune and chronic inflammatory diseases. J Autoimmun. 2017;83:51–61.
  • De Santis M, Ceribelli A, Cavaciocchi F, et al. Effects of type II collagen epitope carbamylation and citrullination in human leucocyte antigen (HLA)-DR4(+) monozygotic twins discordant for rheumatoid arthritis. Clin Exp Immunol. 2016;185:309–319.
  • Selmi C, Cavaciocchi F, Lleo A, et al. Genome-wide analysis of DNA methylation, copy number variation, and gene expression in monozygotic twins discordant for primary biliary cirrhosis. Front Immunol. 2014;5:128.
  • Bogdanos DP, Smyk DS, Rigopoulou EI, et al. Twin studies in autoimmune disease: genetics, gender and environment. J Autoimmun. 2012;38:J156–69.
  • Boehncke WH, Brembilla NC. Unmet needs in the field of psoriasis: pathogenesis and treatment. Clin Rev Allergy Immunol. 2018 Dec;55(3):295–311.
  • Conrad C, Gilliet M. Psoriasis: from pathogenesis to targeted therapies. Clin Rev Allergy Immunol. 2018;54:102–113.
  • Blauvelt A, Chiricozzi A. The Immunologic Role of IL-17 in Psoriasis and psoriatic arthritis pathogenesis. Clin Rev Allergy Immunol. 2018.
  • Ferreira LMR, Meissner TB, Tilburgs T, et al. HLA-G: at the interface of maternal-fetal tolerance. Trends Immunol. 2017;38:272–286.
  • Tincani A, Dall‘Ara F, Lazzaroni MG, et al. Pregnancy in patients with autoimmune disease: A reality in 2016. Autoimmun Rev. 2016;15:975–977.
  • Schreiber K, Nocturne G, Cornec D, et al. Lymphocytes as biomarkers of therapeutic response in rheumatic autoimmune diseases, is it a realistic goal?. Clin Rev Allergy Immunol. 2017.
  • Oktem O, Yagmur H, Bengisu H, et al. Reproductive aspects of systemic lupus erythematosus. J Reprod Immunol. 2016;117:57–65.
  • Lazzaroni MG, Dall‘Ara F, Fredi M, et al. A comprehensive review of the clinical approach to pregnancy and systemic lupus erythematosus. J Autoimmun. 2016;74:106–117.
  • Tedeschi SK, Guan H, Fine A, et al. Organ-specific systemic lupus erythematosus activity during pregnancy is associated with adverse pregnancy outcomes. Clin Rheumatol. 2016;35:1725–1732.
  • Onuora S. Systemic lupus erythematosus: incidence of flare is increased in pregnancy. Nat Rev Rheumatol. 2018;14:248.
  • 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;77:855–860.
  • Nahal SK, Selmi C, Gershwin ME. Safety issues and recommendations for successful pregnancy outcome in systemic lupus erythematosus. J Autoimmun. 2018;93:16–23.
  • Bakshi J, Segura BT, Wincup C, et al. Unmet needs in the pathogenesis and treatment of systemic lupus erythematosus. Clin Rev Allergy Immunol. 2018 Dec;55(3):352–367.
  • Lateef A, Petri M. Managing lupus patients during pregnancy. Best Pract Res Clin Rheumatol. 2013;27:435–447.
  • Clowse MEB, Eudy AM, Kiernan E, et al. The prevention, screening and treatment of congenital heart block from neonatal lupus: a survey of provider practices. Rheumatology (Oxford). 2018;57:v9–v17.
  • Vanoni F, Lava SAG, Fossali EF, et al. Neonatal systemic lupus erythematosus syndrome: a comprehensive review. Clin Rev Allergy Immunol. 2017;53:469–476.
  • Spinillo A, Beneventi F, Locatelli E, et al. Early, incomplete, or preclinical autoimmune systemic rheumatic diseases and pregnancy outcome. Arthritis Rheumatol. 2016;68:2555–2562.
  • Ince-Askan H, Dolhain RJ. Pregnancy and rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2015;29:580–596.
  • Zbinden A, van Den Brandt S, Ostensen M, et al. Risk for adverse pregnancy outcome in axial spondyloarthritis and rheumatoid arthritis: disease activity matters. Rheumatology (Oxford). 2018.
  • Gerosa M, Schioppo T, Meroni PL. Challenges and treatment options for rheumatoid arthritis during pregnancy. Expert Opin Pharmacother. 2016;17:1539–1547.
  • Boodhoo KD, Liu S, Zuo X. Impact of sex disparities on the clinical manifestations in patients with systemic lupus erythematosus: A systematic review and meta-analysis. Medicine (Baltimore). 2016;95:e4272.
  • Jaillon S, Berthenet K, Garlanda C. Sexual Dimorphism in Innate Immunity. Clin Rev Allergy Immunol. 2017.
  • Gomez A, Luckey D, Taneja V. The gut microbiome in autoimmunity: sex matters. Clin Immunol. 2015;159:154–162.
  • Cutolo M, Sulli A, Straub RH. Estrogen metabolism and autoimmunity. Autoimmun Rev. 2012;11:A460–4.
  • Gubbels Bupp MR. Sex, the aging immune system, and chronic disease. Cell Immunol. 2015;294:102–110.
  • Talsania M, Scofield RH. Menopause and Rheumatic Disease. Rheum Dis Clin North Am. 2017;43:287–302.
  • Bove R. Autoimmune diseases and reproductive aging. Clin Immunol. 2013;149:251–264.
  • Mollard E, Pedro S, Chakravarty E, et al. The impact of menopause on functional status in women with rheumatoid arthritis. Rheumatology (Oxford). 2018;57:798–802.
  • Sammaritano LR. Menopause in patients with autoimmune diseases. Autoimmun Rev. 2012;11:A430–6.
  • Eder L, Thavaneswaran A, Chandran V, et al. Gender difference in disease expression, radiographic damage and disability among patients with psoriatic arthritis. Ann Rheum Dis. 2013;72:578–582.
  • Lubrano E, De Socio A, Perrotta FM. Unmet Needs in Axial Spondyloarthritis. Clin Rev Allergy Immunol. 2018 Dec;55(3):332–339.
  • Generali E, Scire CA, Cantarini L, et al. Sex Differences in the Treatment of Psoriatic Arthritis: A Systematic Literature Review. Isr Med Assoc J. 2016;18:203–208.
  • Lubrano E, Perrotta FM, Manara M, et al. The sex influence on response to tumor necrosis factor-alpha inhibitors and remission in axial spondyloarthritis. J Rheumatol. 2018;45:195–201.
  • Hojgaard P, Ballegaard C, Cordtz R, et al. Gender differences in biologic treatment outcomes-a study of 1750 patients with psoriatic arthritis using Danish Health Care Registers. Rheumatology (Oxford). 2018;57:1651–1660.
  • Stober C, Ye W, Guruparan T, et al. Prevalence and predictors of tumour necrosis factor inhibitor persistence in psoriatic arthritis. Rheumatology (Oxford). 2018;57:158–163.
  • Ortolan A, van Lunteren M, Ramiro S, et al. Are gender-specific approaches needed in diagnosing early axial spondyloarthritis? Data from the SPondyloArthritis Caught Early cohort. Arthritis Res Ther. 2018;20:218.
  • Bergstra SA, Allaart CF, Ramiro S, et al. Sex-associated treatment differences and their outcomes in rheumatoid arthritis: results from the meteor register. J Rheumatol. 2018.
  • Krasselt M, Baerwald C. Sex, Symptom Severity, and Quality of Life in Rheumatology. Clin Rev Allergy Immunol. 2017.
  • Castaneda S, Gonzalez-Juanatey C, Gonzalez-Gay MA. Sex and Cardiovascular Involvement in Inflammatory Joint Diseases. Clin Rev Allergy Immunol. 2017 Aug 29. doi: 10.1007/s12016-017-8635-2. [Epub ahead of print].
  • Carreira PE, Carmona L, Joven BE, et al. Gender differences in early systemic sclerosis patients: a report from the EULAR scleroderma trials and research group (EUSTAR) database. Clin Exp Rheumatol. 2018;36(Suppl 113):68–75.
  • Onishi A, Sugiyama D, Kumagai S, et al. Cancer incidence in systemic sclerosis: meta-analysis of population-based cohort studies. Arthritis Rheum. 2013;65:1913–1921.
  • Linden M, Ramirez Sepulveda JI, James T, et al. Sex influences eQTL effects of SLE and Sjogren‘s syndrome-associated genetic polymorphisms. Biol Sex Differ. 2017;8:34.
  • Ramirez Sepulveda JI, Kvarnstrom M, Brauner S, et al. Difference in clinical presentation between women and men in incident primary Sjogren‘s syndrome. Biol Sex Differ. 2017;8:16.
  • Bove R, Chitnis T. The role of gender and sex hormones in determining the onset and outcome of multiple sclerosis. Mult Scler. 2014;20:520–526.
  • Li B, Selmi C, Tang R, et al. The microbiome and autoimmunity: a paradigm from the gut-liver axis. Cell Mol Immunol. 2018 Jun;15(6):595–609.
  • Caminer AC, Haberman R, Scher JU. Human microbiome, infections, and rheumatic disease. Clin Rheumatol. 2017;36:2645–2653.
  • Manasson J, Shen N, Garcia Ferrer HR, et al. Gut microbiota perturbations in reactive arthritis and postinfectious spondyloarthritis. Arthritis Rheumatol. 2018;70:242–254.
  • Zhong D, Wu C, Zeng X, et al. The role of gut microbiota in the pathogenesis of rheumatic diseases. Clin Rheumatol. 2018;37:25–34.
  • Ma HD, Zhao ZB, Ma WT, et al. Gut microbiota translocation promotes autoimmune cholangitis. J Autoimmun. 2018 Dec;95:47–57.
  • Floreani A, Leung PS, Gershwin ME. Environmental Basis of Autoimmunity. Clin Rev Allergy Immunol. 2016;50:287–300.
  • Markle JG, Frank DN, Mortin-Toth S, et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science. 2013;339:1084–1088.
  • Rizzetto L, Fava F, Tuohy KM, et al. Connecting the immune system, systemic chronic inflammation and the gut microbiome: the role of sex. J Autoimmun. 2018;92:12–34.
  • Neuman H, Debelius JW, Knight R, et al. Microbial endocrinology: the interplay between the microbiota and the endocrine system. FEMS Microbiol Rev. 2015;39:509–521.
  • Rosenbaum JT, Silverman GJ. The microbiome and systemic lupus erythematosus. N Engl J Med. 2018;378:2236–2237.
  • Maeda Y, Takeda K. Role of gut microbiota in rheumatoid arthritis. J Clin Med. 2017;6.
  • Bellocchi C, Volkmann ER. Update on the gastrointestinal microbiome in systemic sclerosis. Curr Rheumatol Rep. 2018;20:49.
  • Cossu M, Beretta L, Mosterman P, et al. Unmet Needs in Systemic Sclerosis Understanding and Treatment: the Knowledge Gaps from a Scientist‘s, Clinician‘s, and Patient‘s Perspective. Clin Rev Allergy Immunol. 2018 Dec;55(3):312–331.
  • Choi RY, Asquith M, Rosenbaum JT. Fecal transplants in spondyloarthritis and uveitis: ready for a clinical trial? Curr Opin Rheumatol. 2018;30:303–309.
  • Schorpion A, Kolasinski SL. Can probiotic supplements improve outcomes in rheumatoid arthritis?. Curr Rheumatol Rep. 2017;19:73.
  • Roman P, Estevez AF, Sanchez-Labraca N, et al. Probiotics for fibromyalgia: study design for a pilot double-blind, randomized controlled trial. Nutricion hospitalaria. 2017;34:1246–1251.
  • Vasile M, Corinaldesi C, Antinozzi C, et al. Vitamin D in autoimmune rheumatic diseases: A view inside gender differences. Pharmacol Res. 2017;117:228–241.
  • Crescioli C, Minisola S. Vitamin D: autoimmunity and Gender. Curr Med Chem. 2017;24:2671–2686.
  • Krementsov DN, Asarian L, Fang Q, et al. Sex-specific gene-by-vitamin d interactions regulate susceptibility to central nervous system autoimmunity. Front Immunol. 2018;9:1622.
  • Arber S, McKinlay J, Adams A, et al. Patient characteristics and inequalities in doctors‘ diagnostic and management strategies relating to CHD: a video-simulation experiment. Soc Sci Med. 2006;62:103–115.

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