Proteome abnormalities improve prediction of RA development

Results from a late-breaking study showed that abnormalities in the proteome are a valuable biomarker to predict the development of rheumatoid arthritis (RA), in addition to elevated anti-citrullinated protein antibodies (ACPA).

Although individuals with elevated ACPA have a higher risk to develop RA, most will not do so. Therefore, an additional biomarker for the prediction of RA is urgently needed. Dr Liam O´Neil (University of Manitoba, Canada) evaluated whether abnormalities in the serum proteome may allow for a better prediction of future disease onset. Using SOMAscan array, quantitative levels of 1,307 proteins were determined in serum samples from 17 first-degree relatives of RA patients who developed inflammatory arthritis synovitis after having been followed prospectively for a mean of 3.2 years. All 17 subjects were ACPA+ at time of inflammatory arthritis diagnosis. In each individual, 2 samples were assessed: 1 at the time of inflammatory arthritis onset and 1 at an earlier timepoint. Protein expression was also compared with that in samples obtained from ACPA+ and ACPA- first-degree relatives who did not develop inflammatory arthritis.

Differential expression of 669 proteins was identified between those who developed inflammatory arthritis and those who did not. Of these, a 23-marker panel could be selected that classified patients at risk to develop inflammatory arthritis. The proteins identified included ITGA2B and HIST1H3A (upregulated in preclinical samples) and protease inhibitors SERPINA5 and ITIH4 (downregulated in preclinical samples). In a validation cohort (n=34), this model correctly classified 31/34 samples (91.2% accuracy) with a sensitivity of 95.6% and specificity of 85.7%. The authors conclude that reproducible differences in the serum proteome can be shown in the serum sample of individuals who ultimately developed inflammatory arthritis – even several years before the onset of clinically evident disease.

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   1. O´Neil L et al. Abstract L07. ACR 2019, 9-13 November, Atlanta (GA/USA).

Posted on 4 February 202028 March 2024