Table 1.

Natural history of rheumatoid arthritis.

Phase of initiation of the disease (interaction between genetic-hormonal-environmental factors)			Preclinical RA	Clinical RA
Genetic and epigenetic factors	Hormonal factors	Environmental factors	Immunological changes	Immunological changes
Shared epitope, PTPN22, STAT4, CTLA4, TRAF1, PADI4, FCRL3, TNFIP3 DNA methylation Dysregulated histone marks	Relationship man : woman 4 : 1 Arthritis is improved in the pregnancy but relapse in the postpartum	Microbiota oral, pulmonary and intestinal Smoking Silica dust Obesity Diet	Inadequate response to peptides Expansion of autoreactive T cells and B cells Expansion of antibody isotype usage and class switching Changes in soluble cytokine and chemokine networks Altered Th17 cells and Th17/regulatory T cell ratios	Upregulation of signalling molecules Immune-mediated tissue inflammation Alterations of autoantibodies, such as glycosylation Cellular expansion
			Clinical manifestations	Clinical manifestations
			Presence of autoantibodies (RF, ACPAs) Nonspecific symptoms	Arthritis Bone erosions Systemic symptoms
Forms of intervention
Suspension of smoking Avoid exposure to silica Healthy diet Maintaining an adequate weight Modifications of the microbiota?			In research, the early use of rituximab or abatacept Modifications of the microbiota?	Anti-inflammatory Biological and nonbiological disease-modifying drugs Glucocorticoids