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JHDM1D and HDAC1–3 mRNA expression levels in peripheral blood mononuclear cells of patients with systemic lupus erythematosus

mRNA-Expressionslevel von JHDM1D und HDAC1–3 in peripheren mononukleären Blutzellen von Patienten mit systemischem Lupus eythematodes

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Abstract

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.

Materials and 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).

Conclusion

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.

Zusammenfassung

Hintergrund

Der systemische Lupus eythematodes (SLE) ist eine rezidivierende chronische Autoimmunerkrankung, welche durch die Produktion von Autoantikörpern gegen eine Reihe von nukleären Antigenen sowie durch chronische Entzündung charakterisiert ist. Die Ätiologie des SLE ist das Ergebnis von Interaktionen zwischen genetischen, epigenetischen, hormonellen und Umweltfaktoren. Veränderungen in der Histon-Acetylation und -Methylation tragen zu strukturellen Chromatin-Modifikationen bei.

Zielstellung

Wir untersuchten die Transkriptionslevel der Histon-Demethylase JHDM1D sowie der Histon-Deacetylasen HDAC1, HDAC2 und HDAC3 in peripheren mononukleären Blutzellen (PBMC) bei Patienten mit diagnostiziertem SLE. Des Weiteren wurde der Zusammenhang der JHDM1D-, HDAC1-, HDAC2- und HDAC3-Transkriptionslevel mit Geschlecht, Alter und wichtigen klinischen Manifestationen analysiert.

Material und Methoden

Eine Analyse der quantitativen Echtzeit-Polymerase-Kettenreaktion (RQ-PCR) wurde verwendet, um die JHDM1D-, HDAC1-, HDAC2- und HDAC3-Expressionslevel in PBMC von 30 Patienten mit SLE und einer Kontrollgruppe von 36 gesunden Probanden zu bestimmen.

Ergebnisse

Bei SLE-Patienten wurden im Vergleich zur Kontrollgruppe signifikant niedrigere HDAC2-Transkriptionslevel (p = 0,006785) und signifikant höhere JHDM1D-Transkriptionslevel (p = 0,0000002) sowie HDAC1-Transkriptionslevel (p = 0,010581) festgestellt. Aktive SLE-Patienten wiesen im Vergleich zu nichtaktiven Patienten eine höhere JHDM1D-mRNA-Expression auf (p = 0,005). Zudem korrelierten die JHDM1D-Transkriptionslevel positiv mit der Krankheitsaktivität (r s= 0,368; p = 0,045), während die HDAC2-mRNA-Expression positiv mit der Krankheitsdauer korrelierte (r s= 0,502; p = 0,0047).

Schlussfolgerung

Unsere Analysen bestätigten die Wichtigkeit epigenetischer Veränderungen (Histon-Demethylation und -Acetylation) in der SLE-Ätiologie. Darüber hinaus zeigen unsere Ergebnisse, dass das Vorliegen einiger klinischer Manifestationen, wie eine hämatologische Erkrankung und Anti-Ro-Antikörper, mit einer Dysregulation der Transkriptionslevel der Histon-Demethylase sowie der Histon-Deacetylasen assoziiert sein könnte.

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Acknowledgments

This study was supported by grant No 502-01-01124182-07474, Poznań University of Medical Sciences.

Compliance with ethical guidelines

Conflict of interest. M.J. Nawrocki, A.J. Strugała, P. Piotrowski, M. Wudarski, M. Olesińska, and P.P. Jagodziński state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego St, 60-781, Poznań, Poland

    M.J. Nawrocki, P. Piotrowski & P.P. Jagodziński

  2. Department of Molecular and Systems Biology, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznań, Poland

    A.J. Strugała

  3. Institute of Rheumatology, Warsaw, Poland

    M. Wudarski & M. Olesińska

  4. Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego Street, 02-106, Warsaw, Poland

    P. Piotrowski

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  1. M.J. Nawrocki
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  2. A.J. Strugała
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  3. P. Piotrowski
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  5. M. Olesińska
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  6. P.P. Jagodziński
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Correspondence to M.J. Nawrocki.

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Associations of HDAC1, HDAC2, HDAC3 and JHDM1D mRNA levels with major clinical manifestations of SLE patients (PDF 100kB)

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Nawrocki, M., Strugała, A., Piotrowski, P. et al. JHDM1D and HDAC1–3 mRNA expression levels in peripheral blood mononuclear cells of patients with systemic lupus erythematosus . Z Rheumatol 74, 902–910 (2015). https://doi.org/10.1007/s00393-015-1619-9

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