Monozygotic (MZ) twins are partially concordant for most complex diseases, including autoimmune disorders. Whereas phenotypic concordance can be used to study heritability, discordance suggests the role of non-genetic factors. In autoimmune diseases, environmentally driven epigenetic changes are thought to contribute to their etiology. Here we report the first high-throughput and candidate sequence analyses of DNA methylation to investigate discordance for autoimmune disease in twins. We used a cohort of MZ twins discordant for three diseases whose clinical signs often overlap: systemic lupus erythematosus (SLE), rheumatoid arthritis, and dermatomyositis. Only MZ twins discordant for SLE featured widespread changes in the DNA methylation status of a significant number of genes. Gene ontology analysis revealed enrichment in categories associated with immune function. Individual analysis confirmed the existence of DNA methylation and expression changes in genes relevant to SLE pathogenesis. These changes occurred in parallel with a global decrease in the 5-methylcytosine content that was concomitantly accompanied with changes in DNA methylation and expression levels of ribosomal RNA genes, although no changes in repetitive sequences were found. Our findings not only identify potentially relevant DNA methylation markers for the clinical characterization of SLE patients but also support the notion that epigenetic changes may be critical in the clinical manifestations of autoimmune disease.[Supplemental material is available online at http://www.genome.org. The sequence data from this study have been submitted to the NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo) under accession no. GSE19033.]Human monozygotic (MZ) twins exhibit variable degrees of concordance for complex diseases, such as cancer, cardiovascular diseases, or autoimmune disorders. Whereas concordance rates close to 100% in identical twins apply to coinheritance of mutant genes that are dominant and highly penetrant, most diseases or traits show a concordance in identical twins in the broad range of 5%-75% (Nance 1978). Most of the twin-based studies have focused on the concordance between siblings that has led to the identification of traitspecific genes (Hrubec and Robinette 1984), while less attention has been paid to the degree of discordance, which suggests the participation of factors other than pure genetic changes. Recently, interest has shifted toward exploring the molecular mechanisms involved in determining phenotypic differences. The increasing recognition of the influence of epigenetics in phenotypic outcomes continues to open up new lines of research involving twin studies. DNA methylation and histone modifications, the major sources of epigenetic information, regulate gene expression levels and provide an alternative mechanism for modulating gene function to those arising from genetic changes (Esteller 2008). Interestingly, epigenetic changes are

Purpose of review The aim of this study was to evaluate the relationship between infection with SARS-CoV-2 and autoimmunity. Recent findings Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome (SARS) associated coronavirus 2 (SARS-CoV-2). Although most of the infected individuals are asymptomatic, a proportion of patients with COVID-19 develop severe disease with multiple organ injuries. Evidence suggests that some medications used to treat autoimmune rheumatologic diseases might have therapeutic effect in patients with severe COVID-19 infections, drawing attention to the relationship between COVID-19 and autoimmune diseases. COVID-19 shares similarities with autoimmune diseases in clinical manifestations, immune responses and pathogenic mechanisms. Robust immune reactions participate in the pathogenesis of both disease conditions. Autoantibodies as a hallmark of autoimmune diseases can also be detected in COVID-19 patients. Moreover, some patients have been reported to develop autoimmune diseases, such as Guillain--Barré syndrome or systemic lupus erythematosus, after COVID-19 infection. It is speculated that SARS-CoV-2 can disturb self-tolerance and trigger autoimmune responses through cross-reactivity with host cells. The infection risk and prognosis of COVID-19 in patients with autoimmune diseases remains controversial, but patient adherence to medication regimens to prevent autoimmune disease flares is strongly recommended. Summary We present a review of the association between COVID-19 and autoimmune diseases, focusing on similarities in immune responses, cross-reactivity of SARS-CoV-2, the development of autoimmune diseases in COVID-19 patients and the risk of COVID-19 infection in patients with preexisting autoimmune conditions.