Introduction: Aberrant histone acetylation is increasingly thought to play important roles in the pathogenesis of autoimmune diseases. However, there are very few data on histone acetylation in primary Sjögren's syndrome (pSS). We aimed to investigate whether there was abnormal histones acetylation in patients with pSS.
Methods: We investigated the expressions of histone acetyltransferase (HAT) genes (p300, CREBBP and PCAF) by real-time PCR in the peripheral blood mononuclear cells (PBMCs) of pSS patients. HAT activity and histone H3/H4 acetylation activity were measured by activity kit, and histone H3/H4 acetylation was verified by Western blot (WB). Spearman test was utilized to analyze the association between HAT activity levels and clinical parameters of pSS patients.
Results: The mRNA expressions of p300, CREBBP and PCAF in PBMCs from pSS patients were decreased in comparison with healthy controls (P < 0.05). HAT activity and histone H3/H4 acetylation were reduced in PBMCs from pSS patients (P < 0.05). We found that HAT activity was negatively correlated with CRP (P = 0.040) and TNF-α (P = 0.012), and was positively correlated with C4 (P = 0.041).
Conclusions: Histone hypoacetylation is observed in patients with pSS and is involved in the pathogenesis of pSS.
Key points: • The mRNA expressions of p300, CREBBP and PCAF in PBMCs from pSS patients were decreased in comparison with HCs. • HAT activity and histone H3/H4 acetylation were reduced in PBMCs from pSS patients. • HAT activity was correlated with disease characters. • We show for the first time that the histone hypoacetylation may be involved in the pathogenesis of pSS.
Keywords: Epigenetic; Histone acetyltransferase; Hypoacetylation; Sjögren’s syndrome.
© 2021. International League of Associations for Rheumatology (ILAR).