Systemic inflammation and lymphocyte activation precede rheumatoid arthritis

Area of Science:

• Immunology
• Autoimmune Diseases
• Systems Biology

Background:

• Autoimmune diseases like rheumatoid arthritis (RA) have a subclinical phase.
• Understanding this pre-disease state is crucial for proactive management but is limited by a lack of biological insight.
• Identifying early immune alterations can reveal targets for intervention.

Purpose of the Study:

• To characterize the immune landscape during the at-risk period preceding clinical diagnosis of RA.
• To identify specific cellular and molecular changes that define the subclinical phase of RA.
• To provide tools for exploring this extensive multi-omics dataset.

Main Methods:

• Cross-sectional and longitudinal multi-omics study of peripheral immune cells.
• Analysis of autoantibody-positive individuals at risk for RA.
• Identification of systemic inflammation markers, B cell and T cell populations, monocyte phenotypes, and CD4 T cell transcriptional signatures.

Main Results:

• Systemic inflammation and proinflammatory-skewed B cells were identified.
• Expanded Tfh17-like cells and epigenetic bias in naive T cells were observed.
• Monocytes resembled synovial macrophages, and CD4 T cell features mimicked those affected by abatacept in RA patients.

Conclusions:

• The at-risk state for RA exhibits significant immune alterations prior to clinical diagnosis.
• These findings provide a deeper understanding of RA pathogenesis.
• Targeting these early immune changes may offer opportunities for early intervention to delay or prevent autoimmunity.