The importance of differences; On environment and its interactions with genes and immunity in the causation of rheumatoid arthritis
- PMID: 32176395
- DOI: 10.1111/joim.13058
The importance of differences; On environment and its interactions with genes and immunity in the causation of rheumatoid arthritis
Abstract
The current review uses rheumatoid arthritis (RA) as a prominent example for how studies on the interplay between environmental and genetic factors in defined subsets of a disease can be used to formulate aetiological hypotheses that subsequently can be tested for causality using molecular and functional studies. Major discussed findings are that exposures to airways from many different noxious agents including cigarette smoke, silica dust and more interact with major susceptibility genes, mainly HLA-DR genetic variants in triggering antigen-specific immune reactions specific for RA. We also discuss how several other environmental and lifestyle factors, including microbial, neural and metabolic factors, can influence risk for RA in ways that are different in different subsets of RA.The description of these processes in RA provides the best example so far in any immune-mediated disease of how triggering of immunity at one anatomical site in the context of known environmental and genetic factors subsequently can lead to symptoms that precede the classical inflammatory disease symptoms and later contribute also to the classical RA joint inflammation. The findings referred to in the review have led to a change of paradigms for very early therapy and prevention of RA and to efforts towards what we have named 'personalized prevention'. We believe that the progress described here for RA will be of relevance for research and practice also in other immune-mediated diseases.
Keywords: autoimmunity; disease prediction; disease subsets; gene-environment interactions; personalized prevention; rheumatoid arthritis.
© 2020 The Association for the Publication of the Journal of Internal Medicine.
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References
-
- Parham P. Molecular definition of the transplantation antigens. FEBS J 2018; 285: 2728-45.
-
- Han A, Glanville J, Hansmann L,Davis MM. Linking T-cell receptor sequence to functional phenotype at the single-cell level. Nat Biotechnol 2014; 32: 684-92.
-
- Brodin P, Jojic V, Gao T et al. Variation in the human immune system is largely driven by non-heritable influences. Cell 2015; 160: 37-4.
-
- Brodin P, Davis MM. Human immune system variation. Nat Rev Immunol 2017; 17: 21-9.
-
- Garrod AB. The nature and treatment of gout and rheumatic gout. Alton and Maberly 1859.
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