Aktuelle Rheumatologie
DOI: 10.1055/a-2106-6930
Original Article

Serum Progranulin Levels and Disease Activity in Patients with Axial Spondyloarthritis

Serum-Progranulinspiegel und Krankheitsaktivität bei Patienten mit axialer Spondyloarthritis
Irem Mercan
1   Department of PRM, Rize Kackar State Hospital, Rize, Turkey
,
Pelin Oktayoglu
2   Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Division of Rheumatology, Dicle University, Diyarbakir, Turkey
,
Nuriye Mete
3   Department of Biochemistry, Dicle University, Diyarbakir, Turkey
,
Mehmet Caglayan
2   Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Division of Rheumatology, Dicle University, Diyarbakir, Turkey
› Author Affiliations

Abstract

Background Axial spondyloarthritides (ax-SpA) are a group of chronic systemic diseases of unknown aetiology, affecting mostly young men, with common features such as inflammatory low back pain, axial skeletal involvement, sacroiliitis, and association with HLA-B27. Inflammatory cytokines, mainly TNF-α, play a role in its aetiopathogenesis. Progranulin (PGRN) is thought to be an anti-inflammatory molecule that acts through the TNF-α pathway. In our study, we aimed to investigate the relationship between serum PGRN levels and disease activity in patients with AS.

Material and Methods Forty-five patients between the ages of 18 and 65 who were classified as having ax-SpA according to ASAS classification criteria were included in our study. Forty-five individuals between the ages of 18 and 65 who did not have pregnancy or lactation status, no acute or chronic infection and no malignancy or rheumatic disease were included as the healthy control group. In addition, BASDAI, BASFI, BASMI, ASDAS-CRP, ESR and CRP levels were recorded in the patient group to determine the laboratory and clinical findings of patients with ax-SpA.

Results Mean serum progranulin levels were higher in axial SpA patients compared with the control group (5156.72±1274.34 vs. 4836.50±1422.10), but this result was not statistically significant (p=0.275). Serum progranulin levels were negatively correlated with ESR (p=0.031) but ASDAS-CRP (p=0.407) and BASDAI (p=0.297) values were not correlated with the progranulin levels.

Conclusion Although we found a negative correlation between progranulin and ESR, we did not find any association between progranulin and disease activity in patients with axSpA. There is a need for new and larger studies to be conducted with a higher number of participants in this patient group and to measure serum PGRN levels as well as antibodies against PGRN.



Publication History

Article published online:
17 July 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Dubash S, McGonagle D, Marzo-Ortega H. New advances in the understanding and treatment of axial spondyloarthritis: from chance to choice. Ther Adv Chronic Dis 2018; 9: 77-87
  • 2 Bateman A, Cheung ST, Bennett HPJ. et al. Overview of Progranulin in Health and Disease. Methods Mol Biol 2018; 1806: 3-15
  • 3 Hrabal R, Chen Z, James S. et al. The hairpin stack fold, a novel protein architecture for a new family of protein growth factors. Nat Struct Biol 1996; 3: 747-752
  • 4 Palfree RG, Bennett HP, Bateman A. The Evolution of the Secreted Regulatory Protein Progranulin. PLoS One 2015; 10: e0133749
  • 5 Bhandari V, Palfree RG, Bateman A. Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains. Proc Natl Acad Sci U S A 1992; 89: 1715-1719
  • 6 Plowman GD, Green JM, Neubauer MG. et al. The epithelin precursor encodes two proteins with opposing activities on epithelial cell growth. J Biol Chem 1992; 267: 13073-13078
  • 7 Jian J, Li G, Hettinghouse A. et al. Progranulin: a key player in autoimmune diseases. Cytokine. 2018; 101: 48-55
  • 8 Daniel R, He Z, Carmichael KP. et al. Cellular localization of gene expression for progranulin. J Histochem Cytochem 2000; 48: 999-1009
  • 9 Farag AGA, Shoaib MA, Samaka RM. et al. Progranulin and beta-catenin in psoriasis: an immunohistochemical study. J Cosmet Dermatol 2019; 18: 2019-2026
  • 10 Sam YJ, Cheng BS, Pan MH. HF et al. Progranulin as a Potential Therapeutic Target in Immune-Mediated Diseases. J Inflamm Res 2021; 14: 6543-6556
  • 11 Tang W, Lu Y, Tian QY. et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 2011; 332: 478-484
  • 12 Zhao YP, Liu B, Tian QY. et al. Progranulin protects against osteoarthritis through interacting with TNF-alpha and beta-Catenin signalling. Ann Rheum Dis 2015; 74: 2244-2253
  • 13 Cui Y, Hettinghouse A, Liu CJ. Progranulin: a conductor of receptors orchestra, a chaperone of lysosomal enzymes and a therapeutic target for multiple diseases. Cytokine Growth Factor Rev 2019; 45: 53-64
  • 14 Liu CJ. Progranulin: a promising therapeutic target for rheumatoid arthritis. FEBS Lett 2011; 585: 3675-3680
  • 15 Jian J, Li G, Hettinghouse A. et al. Progranulin. A key player in autoimmune diseases. Cytokine 2018; 101: 48-55
  • 16 Jian J, Konopka J, Liu C. Insights into the role of progranulin in immunity, infection, and inflammation. J Leukoc Biol 2013; 93: 199-208
  • 17 C-j Liu, Bosch X. Progranulin: a growth factor, a novel TNFR ligand and a drug target. Pharmacol Ther 2012; 133: 124-132
  • 18 Wang S, Sun G, Fan P. et al. Distinctive roles of tumor necrosis factor receptor type 1 and type 2 in a mouse disc degeneration model. J Orthop Translat 2021; 3: 62-72
  • 19 Francois RJ, Neure L, Sieper J. et al. Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: detection of tumour necrosis factor alpha in two patients with early disease and transforming growth factor beta in three more advanced cases. Ann. Rheum. Dis. 2006; 65: 713-720
  • 20 Lata M, Hettinghouse AS, Liu CJ. Targeting tumor necrosis factor receptors in ankylosing spondylitis. Ann N Y Acad Sci 2019; 1442: 5-16
  • 21 Rudwaleit M, Landewe R, van der Heijde D. et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty appraisal. Ann Rheum Dis 2009; 68: 770-776
  • 22 van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis: a proposal for modification of the New York criteria. Arthritis Rheum 1984; 27: 361-368
  • 23 Rudwaleit M, van der Heijde D, Landewé R. et al. The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis 2011; 70: 25-31
  • 24 Garrett S, Jenkinson T, Kennedy LG. et al. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 1994; 21: 2286-2291
  • 25 Lukas C, Landewé R, Sieper J. et al. Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009; 68: 18-24
  • 26 Calin A, Garrett S, Whitelock H. et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index J Rheumatol 1994; 21: 2281-2285
  • 27 Jenkinson TR, Mallorie PA, Whitelock HC. et al. Defining spinal mobility in ankylosing spondylitis (AS). The Bath AS Metrology Index. J Rheumatol 1994; 21: 1694-1698
  • 28 Tanaka A, Tsukamoto H, Miloma H. et al. Serum progranulin levels are elevated in patients with systemic lupus erythematosus. Arthritis Res Ther 2012; 14: R244
  • 29 Ichimura Y, Asano Y, Akamata K. et al. Progranulin Overproduction Due to Fli-1 Deficiency Contributes to the Resistance of Dermal Fibroblasts to Tumor Necrosis Factor in Systemic Sclerosis. Arthritis Rheum 2015; 67: 3245-3255
  • 30 Thurner L, Preuss KD, Fadle N. et al. Progranuline antibodies in autoimmune diseases. J autoimmun 2013; 42: 29-38
  • 31 Thurner L, Zaks M, Preuss KD. et al. Progranulin antibodies entertain a proinflammatory environment in a subgroup of patients with psoriatic arthritis. Arthritis Research & Therapy 2013; 15: R211
  • 32 Maury CP, Teppo AM. Tumor necrosis factor in the serum of patients with systemic lupus erythematosus. Arthritis Rheum 1989; 32: 146-150
  • 33 Reinecker HC, Steffen M, Witthoeft T. et al. Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn’s disease. Clin Exp Immunol 1993; 94: 174-181
  • 34 Pan CX, Kinch MS, Kiener PA. et al. PC cell-derived growth factor expression in prostatic intraepithelial neoplasia and prostatic adenocarcinoma. Clin Cancer Res 2004; 10: 1333-1337
  • 35 Cheung PF, Cheng CK, Wong NC. et al. Granulin-epithelin precursor is an oncofetal protein defining hepatic cancer stem cells. PLoS One 2011; 6: e28246 DOI: 10.1371/journal.pone.0028 246.
  • 36 Yamamato Y, Takemura M, Serrero G. et al. Increased serum GP88 (progranulin) concentrations in Rheumatoid Arthritis. Inflammation 2014; 37 DOI: 10.1007/s.10753-014-9911-4.
  • 37 Mac Ewan DJ. TNF receptor subtype signalling: differences and cellular consequences. Cellular Signalling 2002; 14: 477–492; Latta M, Hettinghouse AS, Liu C. Targetting tumor necrosis receptors in ankylosing spondylitis. Ann NY Acad Sci 2019; 1442(1): 5–16
  • 38 Tang W, Lu Y, Tian QY. et al. The growth factor progranulin binds to TNF receptors and is therapeutic agonist in inflammatory arthritis in mice. Science 2011; 332: 478-484
  • 39 Wei J, Fu W, Ding YJ. et al. Progranılin protects against early OA in Mouse and rat models. Arthritis Res Ther 2017; 19: 280
  • 40 Youn BS, Bang SI, Klöting N. et al. Serum progranulin concentrations may be associated with macrophage infiltration into omental adipose tissue. Diabetes 2009; 58: 627-636