Int J Rheum Dis. 2019;00:1–8. wileyonlinelibrary.com/journal/apl | 1 © 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd 1 | INTRODUCTION Ankylosing spondylitis (AS) is a complex rheumatic disease mainly char- acterized by the involvement of the axial skeleton including sacroiliac joint, alongside involvement of the peripheral joints. 1 Although, the environment has a role in the pathogenesis of AS, studies show that genetic factors provide up to 90% of the susceptibility to the disease; half of them are attributable to major histocompatibility complex Received: 14 August 2019 | Revised: 2 December 2019 | Accepted: 6 December 2019 DOI: 10.1111/1756-185X.13783 ORIGINAL ARTICLE P2 receptors mRNA expression profiles in macrophages from ankylosing spondylitis patients and healthy individuals Maryam Akhtari 1,2 | Seyed Jalal Zargar 1 | Mahdi Vojdanian 2 | Amir Ashraf-Ganjouei 2 | Ali Javinani 2 | Elham Hamzeh 2 | Alireza Rezaiemanesh 3 | Ahmadreza Jamshidi 2,4 | Mahdi Mahmoudi 2,4 1 Department of Cell & Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran 2 Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran 3 Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran 4 Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran Correspondence Mahdi Mahmoudi, Rheumatology Research Center, Tehran University of Medical Sciences, Shariati Hospital, Kargar Ave., Tehran, Iran. Email: mahmoudim@tums.ac.ir. Seyed Jalal Zargar, School of Biology, College of Science, University of Tehran, P.O. Box: 141556455, Tehran, Iran. Email: zargar@ut.ac.ir. Funding information Deputy of Research, Tehran University of Medical Sciences, Grant/Award Number: 94-02-41-28991 Abstract Background: Ankylosing spondylitis (AS) is a multifactorial rheumatic disease which mainly involves the axial skeleton. Macrophages and extracellular nucleotides have been shown to contribute to the inflammation process in autoimmune diseases. Membrane-bound purinergic P2 receptors might be involved in the modulation of immune cells in AS. Therefore, we aimed to analyze the messenger RNA (mRNA) expression of P2 receptors in the macrophages of AS patients and healthy controls. Methods: Twenty-three AS patients and 23 age- and sex-matched healthy individuals were included in our study. Whole blood-separated monocytes of study participants were stimulated by macrophage colony-stimulating factor for 7 days and differenti- ated to macrophages. Monocyte and macrophage markers were analyzed by flow cytometry. SYBR green real-time polymerase chain reaction was used to measure the relative expression levels of P2RX 1 , P2RX 2 , P2RX 3 , P2RX 4 , P2RX 5 , P2RX 6 , P2RX 7 , P2RY 1 , P2RY 2 , P2RY 4 , P2RY 6 , P2RY 11 , P2RY 12 , P2RY 13 , P2RY 14 , and PANX1 genes. Results: P2RY 13 and P2RY 6 genes had the highest expression levels in mac- rophages among P2RY genes. P2RY 1 mRNA expression was significantly down- regulated (−1.75 fold) and P2RY 14 was up-regulated (2.6 fold) in macrophages of AS patients compared to healthy individuals. P2RX 4 gene had the highest expression in monocyte-derived macrophages, followed by P2RX 7 and P2RX 1 genes. There was no significant difference in P2X receptor mRNA expression level between macrophages of AS patients and healthy individuals. Conclusions: Our results indicate that AS patients show altered expression levels of P2 receptor genes. Moreover, these changes might be associated with disease activ- ity and patients’ status. KEYWORDS ankylosing spondylitis, extracellular nucleotides, macrophages, P2 receptors