Background/Purpose: Non-conventional T cells (γδ-T and NK-T cells) and natural killer (NK) cells are involved in the regulation of the immune system, and their alteration was previously described in patients with established rheumatoid arthritis (RA). Antibodies against citrullinated proteins (ACPA) precede the manifestation of RA. EULAR characterized individuals with arthralgia suspicious for progression to RA based on their clinical features (clinically suspect arthralgia, CSA). We aimed to study lymphocyte subpopulations in individuals at risk of developing RA.

Methods: Our study included 131 individuals with arthralgia at risk of developing RA (defined as either ACPA+ or meeting CSA definition) and 69 age and gender-matched healthy controls (HC). The percentage and absolute count of CD3bright γδ-T cells, CD3+CD16/56+ NK-T cells, and CD3-CD16/56+ NK cells were evaluated using flow cytometry. Data were analyzed using the Mann-Whitney test or Wilcoxon matched-pairs test and are expressed as median and interquartile range.

Results: Out of 131 individuals with arthralgia (median age 49.01 [40.24-55.65] years, 92% females), 77 were ACPA+, and 85 met the CSA definition (31 of them were ACPA+). The median symptom duration was 12 [7-36] months, CRP 2.27 [0.87-4.24] mg/l; as per definition, there was no evidence of clinical arthritis on examination of 66 joints at baseline. Twenty-one individuals developed arthritis within a median of 8 months of follow-up with a CRP of 9.23 [2.50-14.50] mg/l and a DAS28-CRP score of 4.70 [3.94-5.65] at the time of arthritis manifestation.

Analysis of lymphocyte subpopulations showed a lower percentage of γδ-T (p=0.010), NK-T (p=0.021) and NK (p< 0.001), as well as an absolute count of γδ-T (p=0.004), NK-T (p=0.005) and NK cells (p≤0.001) in all individuals with arthralgia compared to HC. A lower percentage (p=0.002) and absolute count (p≤0.001) of γδ-T cells were confirmed in a subgroup of ACPA+ individuals compared to HC; but no differences were confirmed between ACPA- individuals and HC. Individuals who met CSA criteria irrespective of ACPA status had a lower percentage (p=0.050) and absolute count (p=0.028) of γδ-T cells; however, the differences were more significant between individuals who did not meet CSA criteria compared to HC (percentage p=0.009; absolute count p=0.004). Individuals who developed RA during the follow-up had a lower baseline percentage (p=0.030) and absolute count (p=0.018) of γδ-T cells compared to the individuals who have not yet developed arthritis during our observation; however, there were no changes at the time of RA manifestation.

Conclusion: We identified lower numbers of γδ-T cells, NK cells as well as NK-T cells in individuals at risk of developing RA, and even lower count of γδ-T cells is in individuals who develop the RA in the future. As the altered distribution of these lymphocyte subtypes was previously observed in RA patients, we hypothesize that this dysregulation observed in the preclinical phase may serve as a prognostic marker for future development of RA.

Acknowledgment: NU22-05-00226, MHCR-023728, SVV-260523

« Back to ACR Convergence 2022

ACR Meeting Abstracts - https://acrabstracts.org/abstract/dysregulation-of-%ce%b3%ce%b4-t-cells-in-individuals-at-risk-of-developing-rheumatoid-arthritis/