POS0469 INCREASED CD11C EXPRESSION IN MONOCYTE SUBPOPULATIONS IN ACPA-POSITIVE INDIVIDUALS WITH ARTHRALGIA AND THEIR ASSOCIATIONS WITH ULTRASOUND-DETECTED SYNOVITIS PRECEDING THE ONSET OF ARTHRITIS
Authors: K. Prajzlerová, O. Kryštůfková, P. Hánová, N. Růžičková, H. Hulejova, J. Vencovský, L. Šenolt, M. Filková
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The autoantibodies such as autoantibodies against citrullinated proteins (ACPA) can be detected years before the first onset of rheumatoid arthritis (RA) and their presence in at-risk individuals conferred increased absolute risks of developing clinical arthritis. Clinical characteristics of patients with arthralgia who are considered at risk for RA (clinically suspect arthralgia, CSA) were defined by EULAR to differentiate these from patients with other types of arthralgia. We have previously described a shift from classical to pro-inflammatory non-classical monocyte subpopulations in the peripheral blood of individuals at risk for RA. CD11c plays a role in the production of pro-inflammatory cytokines and is highly expressed in the mononuclear cells of RA patients. <h3>Objectives:</h3> To study monocyte subpopulations and the expression of CD11c in at-risk individuals with arthralgia. <h3>Methods:</h3> Individuals from the At Risk of RA (ARRA) prospective observational cohort were defined as having arthralgia without arthritis on the examination of 66 joints at baseline and being either ACPA+ and/or meeting the EULAR definition of CSA (further CSA+, fulfilling at least 3 out of 7 parameters). Peripheral blood samples at baseline were analyzed by flow cytometry. Monocytes were classified into classical (CD14++CD16-), intermediate (CD14++CD16+/++), and non-classical (CD14-/+CD16++) subpopulations. The membrane expression of CD11c was assessed in each of these subpopulations as a median of fluorescence. Ultrasound (US) synovitis was evaluated using GLOESS (global OMERACT-EULAR score system) and US7 (the German ultrasonography 7) scores. Data were analyzed using Mann Whitney test and Spearman's correlation coefficient and expressed as median and interquartile range [IQR]. <h3>Results:</h3> Out of 207 at-risk individuals with a median symptom duration of 14 months, 46 developed clinical arthritis (progressors) within a median of 8 months of follow-up and after 30.45 [14.55-67.88] months of symptom duration, with CRP 5.50 [2.09-14.10] mg/l and DAS28-CRP score 4.46 [3.10-5.23] at the time of manifestation. Those individuals (n=151) who had not yet progressed to arthritis with symptom duration longer than 12 months at the most recent clinical assessment were defined as non-progressors. In the entire ARRA cohort, there were no statistically significant differences in the percentage of monocyte subpopulations between ACPA+ and ACPA- or CSA+ and CSA- individuals. However, ACPA+ individuals had higher CD11c expression in both classical (p=0.024) and nonclassical (p=0.040) monocyte subpopulations compared to ACPA- individuals. There were no differences in the percentage of monocyte subpopulations between progressors and non-progressors, but a subgroup of progressors who were ACPA+ and met the CSA criteria had significantly higher expression of CD11c in classical (p=0.030) and non-classical (p=0.015) monocytes and a trend towards higher expression of CD11c in intermediate (p=0.062) monocytes compared to all non-progressors. In progressors, the baseline percentage of classical monocytes correlated negatively with baseline assessments: the tender joint count, DAS-CRP score (as per the definition of inclusion criteria in the absence of arthritis), and US-detected subclinical synovitis assessed by both GLOESS and US7 score, whereas the percentage of intermediate and non-classical monocytes correlated positively with all these parameters (Table 1). There were no such correlations of monocyte subpopulations with the abovementioned parameters in non-progressors or progressors at the time of arthritis manifestation. <h3>Conclusion:</h3> We demonstrate higher expression of pro-inflammatory marker CD11c in monocytes of ACPA+ individuals with arthralgia, who are considered to be at high risk of developing RA, especially in ACPA+ progressors meeting the definition for CSA. Moreover, the positive correlation of pro-inflammatory monocyte subsets with subclinical activity preceding the onset of clinical arthritis suggests their potential role in the pathogenesis of RA. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> Projects NU22-05-00226, MHCR-023728, SVV-260638. <h3>Disclosure of Interests:</h3> <b>None declared.</b>