Background/Purpose: To investigate thymic T-cell output, senescence of circulating T-cell subsets and changes of T cell subsets in patients with axial spondylarthritis (aSpA). Results are compared with data from rheumatoid arthritis (RA) patients and healthy controls (HC).

Methods:  Patients with aSpA (n=26; 26.9% female, mean BASDAI 3.2 ±2.1), RA (n=20; 60.0%, mean SDAI 10.2 ±10.2) and HC (n=24; 70.8%) were prospectively enrolled. Naïve and memory CD4+ and CD8+ T-cell subsets were isolated by MACS-technology. DNA was extracted by QIAamp DNA isolation Kit. TREC Analysis was performed with LC 480 Probes Master using established oligonucleotides as primers. Telomere length analysis was performed using LightCycler FastStart DNA Master SYBR Green I with published oligonucleotides as primers for telomere length or for the single copy gene 36B4 as normalizing sequence. The telomere length was calculated by comparison of sample result with a positive control with known telomere length (HEK293 with 5 kbp). FACS analyses were performed on fresh PBMCs in a separate cohort of 25 patients and 24 HC.

Results: aSpA (median age 37.0, range 21.8-69.7 years) and RA (37.0, 21.4-73.6 years) patients did not differ from HC (35.3, 23.3-54.3 years) regarding age and disease duration (aSpA: mean 7.7±6.8, RA 6.4±5.1 years, each with p>0.2). Percentages of circulating TH17, naïve CD45RA+ and memory CD45RO+ CD4+/CD8+ T-cells as well as CD4+FOXP3+ Treg cells did not differ between aSpA patients and healthy controls.

Reduced thymus function as indicated by a lower TREC content in naïve CD3+CD4+CD45RA+ and CD3+CD8+CD45RA+ T-cells was found in aSpA (median 483 copies/ng DNA, range 33-5033 and 462, 15-4467, respectively) and RA patients (355, 0-162800 and 296, 0-71800, respectively) compared to HC (2304, 0-64444 and 2558, 0-103091, respectively; p<0.05 for comparisons between aSpA or RA patients and HC). Trends for an inverse correlation between TREC content in naïve CD4+ or CD8+ T-cells and age were found among RA patients and HC (corr_coeffs ranging from -0.30 to -0.53, p<0.2 for each analysis) but not among aSpA patients (corr_coeffs-0.01-0.07). Shortened telomeres were found in naïve CD45RA+CD4+ and CD8+ (6.24, 5.76-8.13 and 6.15, 5.33-7.56, respectively) as well as memory CD45RO+CD4+ and CD8+ T-cell subsets (5.99, 5.51-8.46 and 6.21, 5.50-7.79, respectively) from aSpA patients compared to HC (CD4+CD45RA+: 7.17, 3.65-8.67, CD8+CD45RA+: 6.99, 3.83-8.47; CD4+CD45RO+: 6.99, 3.70-8.32 and CD8+CD45RO+: 7.20, 3.87-8.06; p<0.05 for each comparison) whereas differences between RA patients and HC concerning telomere length of T-cell subsets did not reach statistical significance.

Conclusion: Thymic T-cell renewal is impaired in aSpA patients. Consequently, increased peripheral T-cell turnover compensates for failing thymus to maintain T-cell homeostasis leading to accelerated telomere erosion and the accumulation of early aged T-cells.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/reduced-thymus-function-and-accelerated-t-cell-aging-in-patients-with-axial-spondylarthritis/