Background/Purpose: Aberrant telomere shortening and DNA damage-responses have been previously described in SSc, here we aim to validate these observations and incorporate them in a functional and clinical relevant framework

Methods: We measured telomere length in peripheral blood leukocytes, monocytes, B cells, myeloid dendritic cells, T cells and plasmacytoid dendritic cells from a total of 103 healthy controls, 121 lcSSc patients and 83 dcSSc patients. In addition, telomere measurements were performed in 21 monozygotic twin pairs with SSc. We finally analyzed apoptosis and telomere gene expression arrays to investigate underlying pathways and used them to stratify patients.

Results: We found that suffering from dcSSc is an independent risk factor for shorter telomeres in full blood cells, which is on the cellular level reflected by significantly shorter telomeres in T cells and pDCs compared to healthy controls and lcSSc (all p<0.001). Based on the analyses of 21 monozygotic twin pairs with SSc we conclude that this seems to be an inborn error in dcSSc, whereas in lcSSc telomere shortening seems to be caused by disease itself. We establish by gene expression arrays that this seems to be mainly caused by aberrant expression of apoptotic genes, of which expression of BIRC5 and P53 have a specificity of 91% to predict dcSSc from a mixed-pool of 72 healthy controls, lcSSc patients, patients with Raynaud’s phenomenom, ANA+ patients and early SSc patients identified by nail-capillaroscopy, making these genes clinically relevant.

Conclusion: Telomere shortening and apoptotic pathways are differentially regulated in lcSSc and dcSSc and provide novel avenues for patient stratification.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/distinctive-patterns-of-telomere-shortening-and-apoptosis-in-limited-and-diffuse-cutaneous-systemic-sclerosis/