Growing evidence shows preclinical autoimmunity among individuals who later develop clinical autoimmune diseases. Autoimmunity in the general population is not uncommon, while autoimmune diseases are infrequent, and little is known about why some people with autoantibodies develop disease and others do not. A better understanding of risk and protective factors for preclinical autoimmunity and the natural history of autoimmunity may provide insights into the development and prevention of autoimmune diseases. Recent studies have identified trends in autoantibody prevalence and associated characteristics, such as age, gender, and environmental exposures. Interpretation of these findings limited by a lack of knowledge on the natural history of autoimmunity in healthy individuals as well as factors that may later impact the development of disease among autoantibody-positive individuals.

This Research Topic, “Risk and Protective Factors in the Natural History of Autoimmunity,” welcomes submissions on all aspects of this continuum, including Original Research and Review articles to help address this question especially those with the following focus:

1. Natural history of autoantibodies and other self-reactive immune components – in those who do not and those who do develop an autoimmune disease:
o Human populations, animal models and other experimental research
o How do immunologic assays, and their advantages and disadvantages, impact the detection and definitions of self-reactive immune components
o IgM isotype vs. IgG isotype serum reactivities of various autoantigens
o Natural autoantibodies, anti-idiotypes, other autoimmune biomarkers
o The roles of autoantibody titers, polyreactivities, and their changes over time

2. Risk and protective factors for autoimmunity:
o Age, sex/gender, reproductive and hormonal factors
o Factors contributing to seroconversion or seroreversion
o The intersection of genetic, environmental, and epigenetic factors
o Infections, both acute and chronic (including latent viral infections (e.g., EBV and CMV) and underlying alterations in IFN-pathways, and h pylori)
o New statistical models to understand immune function/dysfunction pathways
o Novel exposures, mixtures, interactions of multiple factors, life-course exposures
o Role of the microbiome and mucosal origins hypothesis
o Xenobiotic (including endocrine disruptors and industrial chemicals), pharmaceutical, lifestyle, and nutritional factors

3. Autoimmunity associated with other disorders, including:
o Allergy/atopy and associated diseases (e.g., asthma, dermatitis)
o Alzheimer’s/dementia/Parkinson’s disease
o Cancer (including certain ANA staining patterns such as DFS70/LEDGF)
o Cardiovascular disease (e.g., anti-cardiolipin responses)
o Pro-inflammatory/auto-inflammatory conditions

This topical collection is well suited to research and reviews that advance the current scientific frontiers to better understand the natural history and determinants of autoimmunity, including the complex role and interactions of genetic and environmental factors. Simple genetic association studies, case reports, and case-series are not encouraged.

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Frontiers in Immunology

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