Premature senescence of T-cell subsets in axial spondyloarthritis

OBJECTIVE: To investigate the possible occurrence of early thymic failure and premature senescence of naïve and memory T-cells in patients with axial spondyloarthritis (aSpA). METHODS: Prospective, cross-sectional study of consecutive patients with aSpA (n=51), rheumatoid arthritis (RA, n=51) and healthy controls (HCs, n=50). Demographic, clinical and laboratory parameters were collected in all patients and we isolated naïve (CD45RA(+)) and memory (CD45RO(+)) CD4(+) and CD8(+) T-cell subsets by MACS technology. T-cell receptor rearrangement excision circle (TREC) and telomere length were measured by real-time PCR. We used TRECs as a surrogate for thymus function and telomere length as an indicator of cellular senescence. Telomerase activity was analysed with the Telomeric Repeat Amplification Protocols. RESULTS: We observed a premature decline of thymic output in patients with aSpA and patients with RA compared with HCs as indicated by a reduction of TREC levels in naive T-cells (aSpA: age adjusted regression coefficient (reg(coeff)) for CD4(+)CD45RA(+) T-cells −2.566, p=0.023; RA reg(coeff)=−2.844, p=0.008). Telomere length of all CD4(+) and CD8(+) T-cell subsets was reduced in young patients with aSpA compared with HCs, whereas data for patients with RA were comparable with HCs. Telomerase activity was inversely correlated with telomere length in HCs (correlation coefficient (cor(coeff))=−0.532, p<0.001) but not in patients with aSpA (cor(coeff)=−0.056, p=0.697) and RA (cor(coeff)=−0.003, p=0.982). CONCLUSIONS: Our data indicate an age-inappropriate shrinkage of thymic output, an inappropriate shortening of telomeres in young patients with aSpA and an impaired telomerase enzyme in patients with aSpA and RA.