Background/Purpose: Preclinical phases of rheumatoid arthritis (RA), including therapeutic interventions, have been extensively studied. There is a growing focus on individuals at risk for psoriatic arthritis (PsA). We previously observed changes in monocyte subsets in the peripheral blood of individuals at risk for RA. CD11c and HLA-DR reflects monocyte activation and both are involved in inflammatory autoimmune disease mechanisms. The objective of this study was to evaluate their expression on subsets of monocytes in individuals at risk of RA and PsA.

Methods: The study included 284 individuals at risk of RA (having arthralgia with either ACPA positivity and/or meeting EULAR criteria for clinically suspect arthralgia), 37 individuals at risk of PsA (identified via PEST questionnaire and considered at risk based on psoriasis severity) and 57 ACPA-negative healthy controls (HC). All at-risk individuals had no arthritis on the examination of 66 joints at baseline. Peripheral blood samples were analyzed by flow cytometry. Monocytes were categorized into classical (CD14++CD16−), intermediate (CD14++CD16+/++), or nonclassical (CD14−/+CD16++) subsets. The membrane expression of CD11c and HLA-DR was quantified in each subset as median fluorescence intensity. Data were analyzed using the Mann-Whitney test and Kruskal-Wallis test with Dunn’s post-hoc test.

Results: Of the 284 individuals at risk of RA, 52 developed clinical arthritis (progressors) within a median of 9 months of follow-up and after 30.5 months of symptoms duration. Of the remaining individuals without arthritis, the 217 with a symptoms duration longer than 12 months were classified as non-progressors. Among the 37 individuals at risk of PsA (PSA-risk), only 1 progressed to PsA within 7 months of follow-up and after 44 months of symptom duration. There were no significant differences in CD11c or HLA-DR expression between RA progressors and non-progressors in any of the monocyte subsets. However, compared to PsA-risk and HC, individuals at risk of RA (RA-risk) had significantly lower expression of CD11c in all monocyte subsets, regardless of progression to arthritis or ACPA status. PsA-risk individuals showed a trend to higher CD11c expression on classical and nonclassical monocytes compared to HC. Conversely, HLA-DR expression on these monocyte subsets was significantly higher in RA-risk compared to PsA-risk individuals, with a trend towards higher expression on intermediate monocytes. HLA-DR expression was lower in all monocyte subsets in PsA-risk individuals compared to HC.

Conclusion: Individuals at risk of RA exhibit lower expression of the pro-inflammatory integrin CD11c and higher expression of major histocompatibility complex HLA-DR in monocytes compared to individuals at risk of PsA. These findings suggest distinct immune activation mechanisms in RA and PsA, with elevated CD11c expression in PsA-risk individuals potentially reflecting ongoing innate inflammatory responses in the skin, while increased HLA-DR expression in RA-risk individuals may indicate adaptive immune responses involved in RA pathogenesis.Acknowledgements: NU22-05-00226, MHCR-023728, SVV-260638

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/altered-expression-of-cd11c-and-hla-dr-on-monocyte-subsets-in-individuals-at-risk-of-rheumatoid-and-psoriatic-arthritis/