The modulation of inflammatory parameters, Brain-derived neurotrophic factor levels and global histone H4 acetylation status in peripheral blood of patients with Gaucher disease type 1

• Published in: Clinical biochemistry Vol. 50; no. 4-5; pp. 228 - 233
• Main Authors: de Mello, Alexandre Silva, da Silva, Ivy Reichert Vital, Reinaldo, Gustavo Pereira, Dorneles, Gilson Pires, Cé, Jaqueline, Lago, Pedro Dal, Peres, Alessandra, Elsner, Viviane Rostirola, Coelho, Janice Carneiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2017
• Subjects: Acetylation; Adolescent; Adult; beta-Glucosidase - blood; Brain-derived neurotrophic factor (BDNF); Brain-Derived Neurotrophic Factor - blood; Child; Child, Preschool; Female; Gaucher Disease - blood; Gaucher disease type 1 (GD1); Hexosaminidases - blood; Histone H4 acetylation; Histones - metabolism; Humans; Inflammatory parameters; Interleukin-17 - blood; Interleukin-6 - blood; Male; Middle Aged; Protein Processing, Post-Translational; Tumor Necrosis Factor-alpha - blood; Young Adult; Gaucher disease type 1 (GD1); Inflammatory parameters; Histone H4 acetylation; Brain-derived neurotrophic factor (BDNF)
• ISSN: 0009-9120; 1873-2933
• DOI: 10.1016/j.clinbiochem.2016.11.014

Gaucher's disease type 1 (GD1) pathophysiology includes an imbalance on brain-derived neurotrophic factor (BDNF) levels and in the inflammatory system. However, the pathways involved remain poorly understood. The hypothesis of this study is that epigenetic mechanisms might be involved, at least partially, in this phenomenon. This study investigated the BDNF modulation, global histone H4 acetylation and pro- and anti-inflammatory cytokines levels in the peripheral blood of GD1 patients (n=10) when compared with control samples (CS) (n=11). The results showed a significant increase in Chitotriosidase (CT) (p=0.019) and decreased β-glucosidase (GBA) activities (p=0.001) in GD1 samples when compared to CS, for GD1 diagnostic confirmation. Reduced levels of BDNF (p=0.004) and elevated levels of TNF-α (p=0.017) and IL-4 (p=0.035) were also found in the GD group. No significant differences were observed in IL-6 or IL-17a levels between groups (p>0.05). Finally, a trend on higher global histone H4 acetylation levels (p=0.054) was observed in the control group when compared to GD1 individuals. Combined, these results suggest inflammatory cytokines imbalance, reduced BDNF levels and global histone H4 hypoacetylation status in GD type 1 physiopathology. These preliminary findings may open new avenues to introduce therapies and strategies in the preventive management and treatment of this population. •BDNF levels were remarkably reduced in the plasma of GD1 patients.•An inbalance on inflammatory markers was found in the plasma of GD1 patients.•GD1 patients seem to have diminished histone H4 acetylation levels in leukocytes.