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A myelopoiesis gene signature during remission in ANCA associated vasculitis does not predict relapses but seems to reflect ongoing prednisolone therapy
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
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2014 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 175, no 2, 215-226 p.Article in journal (Refereed) Published
Abstract [en]

A myelopoiesis gene signature in circulating leucocytes, exemplified by increased myeloperoxidase (MPO) and proteinase 3 (PR3) mRNA levels, has been reported in patients with active anti-neutrophil cytoplasm antibody associated vasculitis (AAV) and to a lesser extent during remission. We hypothesized that this signature could predict disease relapse. mRNA levels of PR3, MPO, selected myelopoiesis transcription factors (CEBPA, CEBPB, SPIB, SPI1) and microRNAs (miRNAs) from patient and control peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) were analyzed and associated with clinical data. Patients in stable remission had higher mRNA levels for PR3 (PBMCs, PMNs) and MPO (PBMCs). PR3 and SPIB mRNA correlated positively in control but negatively in patient PBMCs. Statistically significant correlations existed between PR3 mRNA and several miRNAs in controls, but not in patients. PR3/MPO mRNA levels were not associated with previous or future relapses but correlated to steroid treatment. Prednisolone doses were negatively linked to SPIB and miR-155-5p, miR-339-5p (PBMCs) and to miR-221, miR-361, miR-505 (PMNs). PR3 mRNA in PBMCs correlated with time since last flare, blood leucocyte count and estimated glomerular filtration rate. Our results show that elevated leucocyte PR3 mRNA levels in AAV patients in remission do not predict relapse. The origin seems multifactorial, but to an important part explainable by prednisolone action. Gene signatures in patients with AAV undergoing steroid treatment should therefore be interpreted accordingly.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014. Vol. 175, no 2, 215-226 p.
Keyword [en]
autoimmunity, microRNA, proteinase 3, rituximab, steroids, transcription factors
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-105185DOI: 10.1111/cei.12236ISI: 000333817000008PubMedID: 24215168OAI: oai:DiVA.org:liu-105185DiVA: diva2:704288
Available from: 2014-03-11 Created: 2014-03-11 Last updated: 2017-12-05Bibliographically approved

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Kurz, TinoWeiner, MariaSkoglund, CamillaBasnet, SandeepEriksson, PerSegelmark, Mårten

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Kurz, TinoWeiner, MariaSkoglund, CamillaBasnet, SandeepEriksson, PerSegelmark, Mårten
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Division of Drug ResearchFaculty of Health SciencesDepartment of NephrologyDepartment of Medical and Health SciencesDivision of Inflammation MedicineDepartment of Rheumatology
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