Abstract
Abstract
Objective
Autoimmune processes in rheumatoid arthritis (RA) begin years before clinical symptom onset. This study aimed to analyse inflammation-related proteins in individuals during the pre-symptomatic phase, in relation to healthy controls and patients with early RA, and their relationship to seroconversion.
Methods
Plasma samples collected prior to symptom onset from individuals who later developed RA (
n
= 419), healthy population controls (
n
= 49), and patients with early RA at diagnosis (
n
= 68) were obtained from a biobank. All samples were analysed for 92 inflammation-related proteins using a proximity extension assay and for anti-CCP2 antibodies and rheumatoid factor. After quality control 77 proteins remained. To identify differentially expressed proteins and enriched pathways, statistical analyses including logistic regression, generalized additive models, and network enrichment analysis was applied.
Results
Four proteins (MMP10, IL6, CCL19, and IL10RB) showed a higher concentration in pre-symptomatic individuals compared to controls (
p
Conclusion
Proteomic alterations are detectable years before RA onset and linked to autoantibody development. Seroconverters differ from those who remain seronegative even in the pre-symptomatic period, supporting the notion that seropositive and seronegative RA represent biologically distinct entities from the earliest stages of the pathogenesis.