Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
The pool of naïve CD4+ T-cells is reduced in patients suffering from systemic lupus erythematosus (SLE). We aimed to study if the occurrence of early thymic involution and premature senescence potentially contributes to reduced naïve CD4+ T-cell numbers.
Peripheral blood mononuclear cells were obtained from 50 SLE patients and 50 healthy controls (HC) in a prospective, cross-sectional study. Prevalence of memory and naïve CD4+ T-cells was assessed by flow cytometry. Naïve CD4+ T-cells were isolated by MACS technology for telomere length and T-cell receptor excision circle (TREC) assessment by real-time PCR. Telomere length was chosen as parameter for cellular senescence and TRECs for the evaluation of thymic function and replicative history. Moreover, telomerase activity was analyzed according to the Telomeric Repeat Amplification Protocols (TRAP). Patients and HCs were separated into two distinct age-groups for analysis of age-dependent differences (≤48 years [SLE n=34, HC n=26]; >48 years [SLE n=16, HC n=24]).
Naïve CD4+ T-cells were significantly reduced in older SLE patients as compared to HCs (SLE 2.06% [0.99-4.47] vs. HC 4.89 [0.55-21.90], p=0.003); no difference was observed between young patients and respective controls. We observed a drastic decline in the number of TRECs in naïve CD4+ T-cells of SLE patients compared to age-matched HCs. TREC numbers were already reduced in younger SLE patients (SLE 168 copies/ng DNA [16-893] vs. HC 2058 [5-64444], p=0.000) and similar results were obtained for older patients (SLE 33 [6-1477] vs. HC 117 [0-2347], p=0.006). Telomeres were shorter in young SLE patients compared to age-matched controls (SLE mean 6.5kbp [±0.5], vs. HC 7.0 [±0.9], p=0.011). In healthy individuals shortening of telomeres induces an increase in telomerase activity resulting in an inverse correlation of telomere length and telomerase activity. We found such a correlation in naïve CD4+ T-cells of HCs (corrcoeff=-0.532, p=0.000) but not in naïve CD4+ T-cells of SLE patients.
Our data indicate extensive replicative history of naive CD4+ T cells of SLE patients leading to a premature decline in telomere length. Unlike in HCs naive CD4+ T cells of SLE patients are unable to respond with increased enzymatic function of telomerase. These findings may partially explain the abnormally low number of naive CD4+ T cells found in older SLE patients.
To cite this abstract in AMA style:Fasching P, Fessler J, Raicht A, Lackner A, Husic R, Graninger W, Schwinger W, Stradner M, Dejaco C. Premature Senescence of Naive CD4+ T-Cells in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/premature-senescence-of-naive-cd4-t-cells-in-systemic-lupus-erythematosus/. Accessed February 28, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/premature-senescence-of-naive-cd4-t-cells-in-systemic-lupus-erythematosus/