Increased serum levels of progranulin (PGRN) in patients with haemophilic arthropathy

Andrzej Kotela; Piotr Wojdasiewicz; Paweł Łęgosz; Sylwia Sarzyńska; Katarzyna Drela; Łukasz Pulik; Beata Kaleta; Monika Kniotek; Jan Borysowski; Łukasz A Poniatowski; Ireneusz Kotela

doi:10.1111/1440-1681.13054

Increased serum levels of progranulin (PGRN) in patients with haemophilic arthropathy

Clin Exp Pharmacol Physiol. 2019 Apr;46(4):373-379. doi: 10.1111/1440-1681.13054. Epub 2018 Dec 21.

Authors

Andrzej Kotela^{1

2}, Piotr Wojdasiewicz^{3

4}, Paweł Łęgosz¹, Sylwia Sarzyńska¹, Katarzyna Drela⁵, Łukasz Pulik¹, Beata Kaleta⁶, Monika Kniotek⁶, Jan Borysowski⁶, Łukasz A Poniatowski^{7

8}, Ireneusz Kotela^{2

9}

Affiliations

¹ Department of Orthopaedics and Traumatology, 1st Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland.
² Department of Orthopaedics and Traumatology, Central Clinical Hospital of the Ministry of the Interior and Administration, Warsaw, Poland.
³ Department of General and Experimental Pathology, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Warsaw, Poland.
⁴ Department of Rehabilitation, Eleonora Reicher National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
⁵ NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
⁶ Department of Clinical Immunology, 1st Faculty of Medicine, Tadeusz Orłowski Transplantation Institute, Medical University of Warsaw, Warsaw, Poland.
⁷ Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Warsaw, Poland.
⁸ Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland.
⁹ Department of Rehabilitation in Disease of the Locomotor System, Faculty of Medicine and Health Sciences, Jan Kochanowski University, Kielce, Poland.

PMID: 30488982
DOI: 10.1111/1440-1681.13054

Abstract

Haemophilia A and B are rarely occurring X chromosome-linked congenital coagulation disorders dominated by spontaneous joint bleedings and chronic synovitis, leading to development of haemophilic arthropathy (HA). Progranulin (PGRN) is a growth factor with anti-inflammatory and immunomodulatory properties. PGRN is an important molecule in the pathogenesis of osteoarthritis (OA) and rheumatological disorders. This study was aimed at investigating the potential role of PGRN in the mechanisms underlying the pathogenesis of HA. The serum levels of PGRN were measured by enzyme-linked immunosorbent assay (ELISA) in patients with end-stage knee joint HA (n = 20) and end-stage primary knee joint OA (n = 20) who met the inclusion and exclusion criteria. The clinical and radiological assessment of disease severity was evaluated by the Knee Society Score (KSS) and Kellgren-Lawrence scale. Median PGRN levels in HA patients was 349.1 ng/mL (232.8-415.6 ng/mL) and in OA patients 148.3 ng/mL (112.1-275.3 ng/mL) with statistically significant differences between both groups (P < 0.015). Further analysis revealed no correlation between PGRN levels and any of the patient demographics and clinical parameters. This study demonstrates increased PGRN serum levels in patients with HA and provides new insights into the mechanisms underlying the pathogenesis of HA indicating a new potential target for therapeutic intervention.

Keywords: haemophilia; haemophilic arthropathy; osteoarthritis; progranulin.