Premature Senescence of Naive CD4+ T-Cells in Primary Sjogren’s Syndrome

Patrizia Fasching¹, Johannes Fessler², Andrea Raicht³, Angelika Lackner², Josef Hermann², Rusmir Husic¹, Sabrina Hammerl⁴, Winfried Graninger², Wolfgang Schwinger³, Christian Dejaco¹ and Martin Stradner¹, ¹Department of Rheumatology and Immunology, Medical University of Graz, Graz, Austria, ²Rheumatology and Immunology, Medical University of Graz, Graz, Austria, ³Division of Pediatric Hemato-Oncology, Medical University of Graz, Graz, Austria, ⁴Medical University of Graz, Graz, Austria

Meeting: ACR/ARHP Annual Meeting 2017

Date of first publication: September 18, 2017

Keywords: Sjogren's syndrome, T cells and Telomeres

Session Information

Date: Tuesday, November 7, 2017

Title: Sjögren's Syndrome II: Pathogenesis, Autoantibodies and T-Cells

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose:

Lymphopenia is a frequent finding in primary Sjögren’s syndrome (pSS) affecting mostly the CD4+ T-cell population. Here we examine possible underlying defects in thymic output and premature senescence of CD4+ T-cells.

Methods:

We included 47 pSS patients and 50 healthy controls (HCs) in a prospective, cross-sectional study. Patients and HCs were separated into two distinct age-groups for analysis of age-dependent differences (≤48 years [SS n=10, HC n=26]; >48 years [pSS n=37, HC n= 24]). Prevalence of T-cell subpopulations was assessed by flow cytometry according to standard surface staining protocols. Naïve CD4+ T-cells were isolated by MACS technology for telomere length and T-cell receptor excision circle (TREC) assessment by real-time PCR. Moreover, telomerase activity was analyzed according to the Telomeric Repeat Amplification Protocols (TRAP).

Results:

We found lower numbers of CD4+ T-cells in pSS patients compared to age matched healthy controls (560/µl vs. 943/µl, p<0.0001). The reduced naïve subset accounted for most of this difference (203/µl vs. 429/µl, P=0.0001). Furthermore, the number of TRECs in naïve CD4+ T-cells was already reduced in young pSS patients (58 copies/ng DNA vs. 2058 copies/ng DNA, p<0.0001) and was furthermore decreased in older patients (14 copies/ng DNA vs. 117 copies/ng DNA, p=0.000) suggesting reduced thymic output or extensive proliferative history. To test for a proliferative history we performed telomere length as well as telomerase activity analysis. Young patients displayed significantly shortened telomeres compared to age-matched controls (6.5kbp vs. 7.0kbp, p=0.011) while telomeres of old patients were not significantly different from age-matched controls. In healthy individuals shorter telomeres resulted in an elevation of telomerase activity, a finding that we could not observe in pSS patients.

Conclusion:

Our data indicate an extensive replicative history of naïve CD4+ T-cells in pSS resulting in premature shortening of telomeres. In contrast to HC, naïve CD4+ T-cells in pSS are unable to induce telomerase activity. This may lead to the reduction of the naïve CD4+ T-cell pool resulting in CD4+ T-cell lymphopenia.

Disclosure: P. Fasching, None; J. Fessler, None; A. Raicht, None; A. Lackner, None; J. Hermann, None; R. Husic, None; S. Hammerl, None; W. Graninger, None; W. Schwinger, None; C. Dejaco, None; M. Stradner, None.

To cite this abstract in AMA style:

Fasching P, Fessler J, Raicht A, Lackner A, Hermann J, Husic R, Hammerl S, Graninger W, Schwinger W, Dejaco C, Stradner M. Premature Senescence of Naive CD4+ T-Cells in Primary Sjogren’s Syndrome [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/premature-senescence-of-naive-cd4-t-cells-in-primary-sjogrens-syndrome/. Accessed .

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