Background/Purpose

Nucleosome is the basic repeating units of chromatin. Each nucleosome is composed of an inner core of histones H3 and H4 and an outer portion of histones H2A and H2B. Protruding tails of the histones can establish contact with other nucleosomes. In addition, these tails can be modified by methyl-, acetyl-, or ubiquitin-groups. DNA surrounds the protein core about 1.5 times on the flat outside and is connected with histones at 14 sites. Nucleosomes are released from cells during apoptosis and necrosis. Although elevated serum nucleosome levels have been described in various autoimmune disorders, only one previous study has shown that systemic sclerosis (SSc) exhibits elevated serum nucleosome levels in less than 15 patients. In addition, correlations of serum nucleosome levels with immunological parameters and organ involvement were not investigated. Although nucleosome contains DNA and histone, which are major autoantigens of various autoimmune diseases, the relationship of nucleosome and disease progression are still unknown. Therefore, we investigated the role of nucleosome in SSc and correlation of serum nucleosome levels with immunological parameters, extent of skin and lung fibrosis, vascular damage, and presence of other organ involvements in SSc.

Methods Serum nucleosome levels were examined in SSc (n=91) and controls (n=20) by enzyme-linked immunosorbent assay. We also examined serum nucleosome levels in bleomycin-induced SSc model mice and phosphate-buffered saline-treated control mice.

Results

Nucleosome levels in limited cutaneous SSc and diffuse cutaneous SSc patients were significantly higher than in normal controls (p<0.0001, respectively). Similarly, in bleomycin-induced SSc model mice, serum nucleosome levels were higher than in control mice (p<0.0001). SSc patients with elevated nucleosome levels had significantly higher modified Rodnan total skin thickness score, high frequency of diffuse cutaneous SSc, and more frequent involvement of pitting scar/ulcer, pulmonary fibrosis, esophagus, heart, kidneys, joints, and muscle than those with normal levels (p<0.05, respectively). Nucleosome levels also significantly correlated inversely with %VC (r=-0.22, p<0.01) and %DLco (r=-0.68, p<0.001) and positively with modified Rodnan total skin thickness score (r=0.58, p<0.001). SSc patients with elevated nucleosome levels had significantly higher frequency of elevated levels of serum IgG and more frequent presence of anti-topoisomerase I and centromere antibodies compared with those with normal levels (p<0.05, respectively). Moreover, in this study, we demonstrated that nucleosome could activate T and B cells which were obtained from SSc patients.

Conclusion These results suggest that elevation of nucleosome levels is associated with the disease severity. In addition, this study is the first to reveal the association of nucleosome levels with various immunological abnormalities in SSc.

---

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/nucleosome-a-basic-repeating-unit-of-chromatin-in-patients-with-systemic-sclerosis-possible-association-with-immunological-abnormalities-via-abnormal-activation-of-t-and-b-cells/