Background: Autoimmune processes in rheumatoid arthritis (RA) begin years before clinical symptom onset.

Objectives: This study aimed to analyze 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 RA at diagnosis (n = 69) were obtained from a biobank. All samples were analyzed for 92 inflammation-related proteins using a proximity extension assay (PEA), and for anti-CCP2 and rheumatoid factor (RF). After quality control 77 proteins remained. To identify differentially expressed proteins and enriched pathways, statistical analyses including logistic regression, generalized additive models (GAMs), and network enrichment analysis was applied.

Results: Four proteins (MMP10, IL-6, CCL19, and IL10RB) showed a higher concentration in pre-symptomatic individuals compared to controls (p < 0.05). Twelve proteins were associated with seropositivity in the preclinical phase and network enrichment analysis of these revealed associated pathways related to the complement system and cytokine activity. Three proteins (CXCL10, CCL7, and CDCP1) were consistently associated with seroconversion, and showed increasing trends approaching symptom onset in individuals who seroconverted, but not in individuals who remained seronegative.

Conclusions: 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.

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: None declared.