title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Undergraduate Program in Bioscience and Rehabilitation, Methodist University - IPA, Porto Alegre, RS, Brazil. Electronic address: melloas@gmail.com.
authors.forename: Alexandre Silva
authors.initials: AS
authors.lastname: de Mello
authors.affiliation: Undergraduate Program in Bioscience and Rehabilitation, Methodist University - IPA, Porto Alegre, RS, Brazil.
authors.forename: Ivy Reichert Vital
authors.initials: IR
authors.lastname: da Silva
authors.affiliation: Undergraduate Rehabilitation Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Gustavo Pereira
authors.initials: GP
authors.lastname: Reinaldo
authors.affiliation: Federal University of Health Sciences of Porto Alegre, Department of Basic Health Sciences, Cellular and Molecular Immunology Laboratory, RS, Brazil.
authors.forename: Gilson Pires
authors.initials: GP
authors.lastname: Dorneles
authors.affiliation: Undergraduate Program in Biological Sciences: Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Jaqueline
authors.initials: J
authors.lastname: Cé
authors.affiliation: Undergraduate Rehabilitation Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Pedro Dal
authors.initials: PD
authors.lastname: Lago
authors.affiliation: Undergraduate Program in Bioscience and Rehabilitation, Methodist University - IPA, Porto Alegre, RS, Brazil; Federal University of Health Sciences of Porto Alegre, Department of Basic Health Sciences, Cellular and Molecular Immunology Laboratory, RS, Brazil.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Peres
authors.affiliation: Undergraduate Program in Bioscience and Rehabilitation, Methodist University - IPA, Porto Alegre, RS, Brazil.
authors.forename: Viviane Rostirola
authors.initials: VR
authors.lastname: Elsner
authors.affiliation: Undergraduate Program in Biological Sciences: Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Janice Carneiro
authors.initials: JC
authors.lastname: Coelho
mesh_terms: D000107:Acetylation; D000293:Adolescent; D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005776:Gaucher Disease / Q000097:blood*; D006596:Hexosaminidases / Q000097:blood; D006657:Histones / Q000378:metabolism*; D006801:Humans; D020381:Interleukin-17 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011499:Protein Processing, Post-Translational; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult; D001617:beta-Glucosidase / Q000097:blood
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D006657:Histones; C508717:IL17A protein, human; C508600:IL6 protein, human; D020381:Interleukin-17; D015850:Interleukin-6; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C579455:BDNF protein, human; D006596:Hexosaminidases; C086400:chitotriosidase; D001617:beta-Glucosidase
keywords: Brain-derived neurotrophic factor (BDNF); Gaucher disease type 1 (GD1); Histone H4 acetylation; Inflammatory parameters