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

Methods: Our study included 71 individuals with arthralgia at risk of developing RA based on ACPA positivity and/or meeting CSA definition and 70 age and gender matched healthy controls (HC). Whole blood samples were analysed by flow cytometry. The % and absolute count of CD3+ T cells and subsequently CD3-CD16/56+ NK cells, CD3+CD16/56+ NK-T cells and CD3bright γδ-T cells were evaluated in CD45+CD14- lymphocyte population. Data were analysed using Mann Whitney test.

Results: Out of 71 individuals with arthralgia (mean age 46.33±12.17 years; 93% females), 46 were ACPA+ and 46 met CSA definition (22 of them were ACPA+). Median symptom duration was 12.5 months [IQR=53], CRP 2.94 mg/L [IQR=3.55 and DAS28-FW score 2.38 [IQR=1.53] that was used as a surrogate parameter of disease activity. As per definition, there was no evidence of clinical arthritis on examination of 66 joints at baseline. Thirteen individuals developed RA within a median of 4 months of follow up.

Analysis of lymphocyte subpopulations showed higher %CD3+ T cells (p=0.004) and lower %NK (p=0.005), %NK-T (p=0.043) as well as absolute count of NK (p≤0.001), NK-T (p=0.012) and γδ-T cells (p=0.027) in all individuals with arthralgia compared to HC. Similarly, higher %CD3+ T cells (p=0.015) and lower %NK (p=0.009), %NK-T (p=0.040) and absolute count of NK (p=0.001), NK-T (p=0.008) and γδ-T cells (p=0.017) were confirmed in a subgroup of ACPA+ individuals (especially those who also met CSA criteria) compared to HC. Also individuals who met CSA criteria irrespective of ACPA status had higher %CD3 T cells (p=0.010) and lower %NK cells (p=0.002) and absolute count of NK (p=0.004), NK-T (p=0.031) and γδ-T cells (p=0.046) compared to HC. Moreover, absolute count of γδ-T cells in individuals with arthralgia negatively correlated with disease activity score DAS28-FW (r=-0.245, p=0.040). There were no differences in lymphocyte subsets in individuals who have developed RA as yet and patients with arthralgia or at the time of RA manifestation.

Conclusion: We show lower numbers of NK cells as well as NK-T and γδ-T cells in individuals at risk of developing of RA irrespective of autoantibody or clinical definition. The decrease of non-conventional T cells was observed despite the increased percentage of the classical T cells. The altered distribution of these lymphocyte subtypes was previously described in established RA. We hypothesize that the dysregulation observed in at-risk individuals may reflect a predisposition leading to further development of RA.

Acknowledgement: Projects AZV-17-32612A and MHCR 023728

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