JHDM1D and HDAC1-3 mRNA expression levels in peripheral blood mononuclear cells of patients with systemic lupus erythematosus.
BACKGROUND
Systemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disease characterized by production of autoantibodies against a series of nuclear antigens and by chronic inflammation. The etiology of SLE is the result of interactions between genetic, epigenetic, hormonal, and environmental factors. Changes in histone acetylation and methylation contribute to structural chromatin modifications.


OBJECTIVE
We studied the histone demethylase JHDM1D and histone deacetylases HDAC1, HDAC2, and HDAC3 transcript levels in peripheral blood mononuclear cells (PBMCs) from patients diagnosed with systemic lupus erythematosus (SLE). Furthermore, the association of JHDM1D, HDAC1, HDAC2, and HDAC3 transcript levels with gender, age, and major clinical manifestations were analyzed.


METHODS
Real-time quantitative polymerase chain reaction (RQ-PCR) analysis was used to determine JHDM1D, HDAC1, HDAC2, and HDAC3 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) from 30 patients with SLE and 36 healthy controls.


RESULTS
Significantly lower HDAC2 transcript levels (p = 0.006785) and significantly higher JHDM1D (p = 0.0000002) and HDAC1 (p = 0.010581) transcript levels in SLE patients were observed compared with healthy controls. Higher JHDM1D mRNA expression was detected in active SLE patients when compared with inactive patients (p = 0.005). Furthermore, the JHDM1D transcript levels were positively correlated with disease activity (r(s) = 0.368, p = 0.045), while HDAC2 mRNA expression was positively correlated with disease duration (r(s) = 0.502, p = 0.0047).


CONCLUSIONS
Our analyses confirmed the importance of epigenetic alterations (histone demethylation and acetylation) in SLE etiology. Moreover, our results suggest that the presence of some clinical manifestations, like hematological disease and anti-Ro antibody, might be associated with the dysregulation of histone demethylase and deacetylases mRNA expression levels.
Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego St, 60-781, Poznań, Poland. mjnawrocki@ump.edu.pl.
M J
MJ
Nawrocki
Department of Molecular and Systems Biology, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznań, Poland.
A J
AJ
Strugała
Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego St, 60-781, Poznań, Poland.|Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego Street, 02-106, Warsaw, Poland.
P
P
Piotrowski
Institute of Rheumatology, Warsaw, Poland.
M
M
Wudarski
Institute of Rheumatology, Warsaw, Poland.
M
M
Olesińska
Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego St, 60-781, Poznań, Poland.
P P
PP
Jagodziński
D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006655:Histone Deacetylases / Q000097:blood* / Q000235:genetics; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000097:blood* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D012333:RNA, Messenger / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D015415:Biomarkers; D012333:RNA, Messenger; D056484:Jumonji Domain-Containing Histone Demethylases; C548973:KDM7A protein, human; D006655:Histone Deacetylases
Antigens, nuclear; Epigenesis, genetic; Histone deacetylases; Histone demethylases; Histone modifications