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Abstract Number: 3006

Cell-Free Circulating DNA in Systemic Sclerosis: Increased Levels and Global Cytosine Hypomethylation

Shadia Nada1, Omar Oraibi2, Farouk Abu Alhana2, Nawaf Almeshal2, Yongqing Wang2, Nezam Altorok3 and Bashar Kahaleh4, 1Internal Medicine, Divison of Rheumatology, The University of Toledo, Toledo, OH, 2The University of Toledo, Toledo, OH, 3Internal Medicine, Division of Rheumatology, The University of Toledo, Toledo, OH, 4Medicine/Rheumatology, The University of Toledo, Toledo, OH

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: DNA, Epigenetics, methylation, scleroderma and systemic sclerosis

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Session Information

Date: Tuesday, November 10, 2015

Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's - Pathogenesis, Animal Models and Genetics Poster II

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Systemic sclerosis (SSc) is an autoimmune disease characterized by endothelial dysfunction, vascular injury, and activation of fibroblasts leading to organ fibrosis. The precise etiology of SSc is not clear. We sought to study circulating cell-free DNA (cfDNA) and characterize it in an initial effort to determine if cfDNA is a useful biomarker in SSc.

Methods: We measured levels of cfDNA in the serum of 20 patients with SSc (13 limited cutaneous SSc, 7 diffuse cutaneous SSc) compared to 20 age-, sex-, and ethnicity-matched controls. The average age was 57.8 and 52.3 years for patients with SSc and controls, respectively (P= 0.10). The majority of subjects in this study were female (n= 17), and Caucasians (n= 19). Modified Rodanan’s skin score (mRSS) was 6.5 and 20.2 for patients with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc), respectively.  Moreover, we measured global methylation level of Cytosine in cfDNA by directly quantifying levels of 5-methylcytosine using 5-methylcytosine specific capture antibody.

Results: We demonstrate an increase in cfDNA level in patients with SSc (262.1 ng/ml) compared to healthy controls (65.9 ng/ml) (P= 0.027). The average level of cfDNA in lcSSc was (134.03 ng/ml) (P = 0.004), and (463.76 ng/ml) in dcSSc (P= 0.022). We did not find a correlation between level of cfDNA and mRSS in each subset, clinical manifestations, or type of organ involvement. We used same amount of cfDNA from each sample to measure 5-methylcytosine, and we demonstrate that cytosine methylation was significantly lower in patients with SSc (29.1%) compared to controls (54.3%) (P = 0.047). There was no significant difference in cytosine methylation between the two subsets of SSc.

Conclusion:

We demonstrate increased level of cfDNA in sera of patients with SSc, especially in patients with dcSSc in association with global hypomethylaiton of cytosine. We did not find a correlation between level of cfDNA and mRSS and/or clinical features of SSc. The origin, functional effect and suitability of cfDNA as a biomarker in SSc need further investigation.


Disclosure: S. Nada, None; O. Oraibi, None; F. Abu Alhana, None; N. Almeshal, None; Y. Wang, None; N. Altorok, None; B. Kahaleh, None.

To cite this abstract in AMA style:

Nada S, Oraibi O, Abu Alhana F, Almeshal N, Wang Y, Altorok N, Kahaleh B. Cell-Free Circulating DNA in Systemic Sclerosis: Increased Levels and Global Cytosine Hypomethylation [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/cell-free-circulating-dna-in-systemic-sclerosis-increased-levels-and-global-cytosine-hypomethylation/. Accessed .
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