New study reveals rheumatoid arthritis begins long before symptoms, opening door to prevention

Good news!

"... It silently starts years earlier. RA is a debilitating autoimmune disease that causes painful joint inflammation and damage. The new research reveals that people at risk for RA experience dramatic immune system changes long before they feel symptoms. During this early phase, their bodies fight an autoimmune battle invisibly. ..."

From the editor's summary and abstract:

"Editor’s summary

Individuals who go on to develop rheumatoid arthritis (RA) experience a stage of disease development before clinical onset where they develop anticitrullinated protein antibodies (ACPAs). However, not all ACPA+ individuals go on to develop clinical RA. Here, He et al. investigated what distinguished those individuals who are ACPA+ and go on to develop disease. They found that systemic inflammation and dysregulation of the B and T cell pools during the at-risk stage were associated with subsequent RA development. These data offer insights into the immune system in individuals who go on to develop RA and may enable the development of treatments to prevent RA before clinical disease. ...

Abstract

Rheumatoid arthritis (RA) is preceded by an at-risk stage of disease that can be marked by the presence of anticitrullinated protein antibodies (ACPAs) but the absence of clinically apparent synovitis (clinical RA). Preemptive intervention in at-risk individuals could prevent or delay future tissue damage; however, the immunobiology of this stage is unclear.

Using integrative multiomics, we longitudinally profiled at-risk individuals, where one-third of participants developed clinical RA on study. We found evidence of systemic inflammation and signatures of activation in naïve T and B cells of at-risk individuals.

During progression to clinical RA, proinflammatory skewing of atypical B cells and expansion of memory CD4 T cells with signatures of activation and B cell help were present without elevations in circulating ACPA titers. Epigenetic changes in naïve CD4 T cells suggested a predisposition to differentiate into effector cells capable of B cell help.

These findings characterize pathogenesis of the ACPA+ at-risk stage and support the concept that the disease begins much earlier than clinical RA. Additionally, an extensive immune resource of the at-risk stage and progression to clinical RA with interactive tools was developed to enable further investigation."

New study reveals rheumatoid arthritis begins long before symptoms, opening door to prevention  - Allen Institute "The seven-year study reveals early-warning signs that could help doctors catch the disease before it starts, potentially saving patients years of pain and disability"

Systemic Inflammation in At-Risk Individuals Advancing to Clinical Rheumatoid Arthritis

Progression to rheumatoid arthritis in at-risk individuals is defined by systemic inflammation and by T and B cell dysregulation (no public access)