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The goal of this research topic is to stimulate research and creative thinking about involvement of epigenetics in autoimmune disease development and progression by providing a comprehensive collection of articles that cover our current knowledge as well as articles that provide insights on new avenues of ...

The goal of this research topic is to stimulate research and creative thinking about involvement of epigenetics in autoimmune disease development and progression by providing a comprehensive collection of articles that cover our current knowledge as well as articles that provide insights on new avenues of autoimmune disease research in relation to epigenetics. In addition, we want articles that discuss epigenetic commonalities and differences between autoimmune diseases, such as comparing systemic lupus erythematosus (SLE), Sjögren’s syndrome (SjS), and rheumatoid arthritis (RA). This research topic will focus on the role of epigenetics in autoimmune diseases including mechanisms, initiation, progression, diagnostic criteria, biomarkers, and potential therapeutic approaches. Such comparative analysis and discussion can assist in identifying new biomarkers, improving diagnostic criteria, support refinement of new hypotheses, and describe new therapeutic approaches.

Epigenetics can be defined as reversible control of gene expression. Epigenetic control of gene expression involves nucleic acid modifications (e.g., DNA methylation), protein modifications (e.g., histone acetylation), micro-RNA expression, long non-coding RNAs (lncRNA), expression of gene activators and suppressors (e.g., the methylated DNA capping protein, MeCP2), counter ion levels (e.g., polyamines), chromatin dynamics (e.g., B-DNA to Z-DNA transitions), and co-localization of genes. Other events can have links to epigenetic disruption, such as signaling pathways, apoptosis, NETosis and cell surface exposure of antigens, and so they may be relevant in the discussions.

Progress in our understanding of autoimmune disease mechanisms has been difficult and, going forward, will still require substantial work for successful development of accurate and timely diagnosis as well as development of properly targeted therapeutics (i.e., effective and with minimal off-target interactions). Difficulties in autoimmune disease research arise from the complexity and variability of these diseases, which hampers our conception and testing of mechanistic hypotheses. Discerning critical events at the cellular level is complicated by the fact that it may be only a minority of cells that have passed a threshold into an anomalous state, whether that is control of T cells, B cells, antigen-presenting cells, or even cells unrelated to immune functions. Autoimmune diseases vary in their triggers, innate and adaptive immune involvement, symptoms, organ involvement, age of onset, progression, gender bias, autoantigens targeted, therapeutic approaches and genetic associations. Each of these could be interesting discussions with regards to epigenetics. As far as the scope of autoimmune diseases, there are more than 100 diseases currently defined as autoimmune diseases and dozens of other diseases that are suspected of having risk for autoimmune complications (e.g., Alzheimer’s disease with anti-amyloid β antibodies). There can be overlap in the autoimmune diseases that complicates differential diagnosis since some autoantigens can appear in several different autoimmune diseases (e.g., SSA/Ro can be an autoantigen in SjS, systemic sclerosis, and other diseases) and one patient may have more than one autoimmune disease (e.g., SLE as a primary disease with SjS as a secondary disease).

There is agreement that genetics, environmental triggers, and epigenetics are important contributing factors in autoimmune diseases, combining to affect cellular and immune system homeostasis. The importance of epigenetics in autoimmune diseases arises from the fact that epigenetics can connect the genome to the phenotype in cellular stress response to environmental triggers.

We are requesting contributions discussing Original Research, Reviews, Hypotheses, or Perspectives. The scope can include epigenetics, diagnostic criteria, treatments, demographics, and other aspects related to epigenetics in autoimmune disease development.

For this Research Topic, we call for papers addressing the many questions that arise, such as:

- What novel insights have emerged recently regarding disease mechanisms, particularly in relation to epigenetics?
- Are there comparable epigenetic anomalies among multiple autoimmune diseases?
- What do we know about epigenetics in the relationship of various autoimmune disease combination, such as primary SjS versus secondary SjS in SLE?
- What are the earliest epigenetic-related events in specific autoimmune diseases and how does each disease progress?
- How can various epigenetic factors contribute to specific autoimmune diseases (DNA methylation, histone modifications, RNAs, other factors)?
- What is the significance of specific autoantigens in relation to epigenetics?
- Can epigenetics explain the female bias and/or age bias in some autoimmune diseases?
- What new therapeutic approaches have arisen targeting epigenetics in autoimmune diseases?
- Are epigenetic and autoimmune aspects emerging in other diseases, diseases not previously considered to be autoimmune diseases?

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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