AB0028 EXPRESSION OF FATTY ACID TRANSPORTERS AND FREE FATTY ACID UPTAKE IN CD8+ T CELLS IN AUTOIMMUNE ARTHRITIS PATIENTS
Authors: S. Keck, F. V. Kraus, H. M. Lorenz, M. Souto-Carneiro
Journal: Annals of the Rheumatic Diseases (2021)

Background: RA CD8+ T cells (CD8s) have been shown to vastly contribute to tissue damage and RA disease activity by presenting and maintaining an active effector phenotype promoting autoinflammation. In order to meet their high metabolic requirements RA CD8s alter not only their glycolytic and glutaminolytic profiles, but also rely on increased lipid metabolism characterized by increased free fatty acid (FFA) uptake and lipid biosynthesis. Objectives: In order to classify the importance of lipid metabolism in RA CD8s in terms of initiation and perpetuation of effector functions and therefore exploring potential novel therapy targeting points or biomarkers additional investigations have to been made. By analysing FFA uptake and the expression of free fatty acid transporters (FAT) upon TCR-stimulation in RA, PsA, SpA patients and healthy controls (HC), we aimed to further characterize the importance of RA CD8s´ lipid metabolism. Methods: Blood samples from 23 RA patients, 22 SpA patients, 20 PsA patients and 7 HC recruited at Heidelberg University Hospital were processed via negative magnetic separation selection to obtain purified CD8s. CD8s were cultured for 72 hours in [1,6-13C] glucose containing medium in the presence of anti-CD3 and anti-CD28. FFA uptake was measured by Palmitate-Bodipy 488 staining (ThermoFisher), the expression of FAT CD36, FABP4 and GPR84 besides CD69, CD36, CD45RA, CD3 and CD8 were assessed by FACS analysis. Ethic approval NR: S-096/2016. Results: The intake of the FFA palmitate by CD8s was higher in all patients groups than in HC (p &lt; 0,05). In all three diseases´ stimulated CD8s, unlike in the HC group, the expression of GPR84 was inversely correlating to the expression of CD69 (Spearman r &lt; -0,62). In patient´s stimulated CD8s the expression of GPR84 tended to be lower in RA and PSA effector memory (EM) CD8s. In RA and HC the expression of FABP4 tended to be lower in the naive CD8+ subset when compared to the effector subset. HC naive and effector CD8+ subsets had a higher expression of CD36 than in the patient groups. In RA and SPA patients the expression of FAT correlated with clinical variables. In RA DAS28 and CRP inversely correlated with CD36 (MFI), and disease duration with FABP4 as well. In SPA CRP and BASDAI inversely correlated with FABP4 while disease duration had a negative correlation with CD36 (MFI). GPR84 (MFI) had an inverted relationship to BASDAI. While the BMI was directly correlated with the expression of CD36 in RA, this relationship was inverted in SPA. Conclusion: A high free fatty acid uptake seems to characterize autoimmune arthritis CD8+ T cells. The gain of effector functions appears to be connected to changes in the expression of different fatty acid transporters on the surface of CD8+ T cells. The correlation between the expression of fatty acid transporters and clinical parameters (specially disease activity scores) in RA and SPA suggests that they could potentially be used as biomarkers for disease activity and progression. Acknowledgements: We thank all the individuals involved in the study for their participation. Disclosure of Interests: None declared