• Users Online: 227
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 18  |  Issue : 3  |  Page : 359-362

Serum level of progranulin in patients with psoriasis and its relation to disease severity


1 Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Assiut University, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Assiut University, Egypt
3 5th Year Medical Student, Assiut University, Egypt

Date of Submission21-Mar-2020
Date of Decision15-May-2020
Date of Acceptance07-Jul-2020
Date of Web Publication30-Oct-2020

Correspondence Address:
Reham M Abdel Gaber
Department of Dermatology and Venereology, Assiut University, Egypt, Assiut
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AZMJ.AZMJ_56_20

Rights and Permissions
  Abstract 


Background Studies have identified progranulin (PGRN) as a proinflammatory and anti-inflammatory protein. Data from other several inflammatory diseases suggest the role of this adipokine in psoriatic pathophysiology.
Objective The aim was to investigate serum levels of PGRN in patients with psoriasis compared with healthy controls, and to consider their relation to disease duration, disease severity, and obesity markers.
Patients and methods Serum PGRN concentrations were measured in 37 patients with active plaque-type psoriasis and 25 healthy controls by using specific enzyme-linked immunosorbent assays.
Results Patients with psoriasis showed higher levels of serum PGRN compared with healthy controls (P<0.033). Concentrations of serum PGRN showed significant positive correlation with Psoriasis Area and Severity Index score, BMI, and waist circumference (P<0.001).
Conclusion Serum PGRN could be a useful biomarker of psoriasis severity and could be a potential target for new therapies for psoriasis.

Keywords: BMI, progranulin, psoriasis


How to cite this article:
Abdel Gaber RM, Hefny RM, Kamal El Din TM, Sotohy RS, Abdel Moez SI. Serum level of progranulin in patients with psoriasis and its relation to disease severity. Al-Azhar Assiut Med J 2020;18:359-62

How to cite this URL:
Abdel Gaber RM, Hefny RM, Kamal El Din TM, Sotohy RS, Abdel Moez SI. Serum level of progranulin in patients with psoriasis and its relation to disease severity. Al-Azhar Assiut Med J [serial online] 2020 [cited 2020 Dec 4];18:359-62. Available from: http://www.azmj.eg.net/text.asp?2020/18/3/359/299573




  Introduction Top


Psoriasis is a chronic autoimmune disorder affecting the skin, characterized by epidermal hyperproliferation, inflammation, and angioneogenesis. The metabolic state of patients with psoriasis may differ from those with other chronic inflammatory diseases. There is a proven association between obesity, psoriasis severity [1], and an increased risk of cardiovascular disease [2].

White adipose tissue located beneath the skin may contribute to the cutaneous inflammation by secreting adipokines and cytokines [3]. Abnormal cutaneous and systemic expression of adipokines and cytokines could influence the activation and differentiation of keratinocytes as well as immune cells contributing to the development of psoriatic lesions [4].

Progranulin (PGRN), also known as proepithelin and granulin/epithelin precursor, is a glycoprotein of 576 amino acids in humans [5]. PGRN is highly expressed in various cells such as epithelial cells, certain types of neurons, and macrophages, and plays an important role in various physiological and disease processes including wound repair, bone and neuro-regeneration, hematopoiesis, tumor genesis, proliferation, and inflammation [6].

Studies have identified PGRN as a proinflammatory and anti-inflammatory protein. For instance, it plays a proinflammatory role in obesity, insulin resistance, dyslipidemia, and metabolic syndrome, while it exerts anti-inflammatory effects in wound repair, central nervous system arthritis, acute ischemia–reperfusion injury, and psoriasis [7].

Circulating PGRN levels correlate with BMI, total body fat mass, and visceral fat area; this suggests that PGRN reflects chronic inflammation in obesity. Moreover, it was found that PGRN concentrations increased by1.4-fold in patients with type 2 diabetes [8].

It was also found that PGRN was upregulated in human psoriatic lesions and exerts anti-inflammatory function in psoriasis-like lesions of tissue plasminogen activator (TPA)-treated WT mice [7]; however, the function of PGRN in the immune system in psoriasis has not been clearly identified and elaborated on [9].

Few data exist on PGRN in the context of psoriasis. However, data from other inflammatory diseases suggest the possible role of this adipokine in psoriatic pathophysiology.


  Patients and methods Top


Thirty-seven consecutive patients with active plaque-type psoriasis attending the dermatology outpatient clinic of The Department of Dermatology, Venereology and Andrology, Assiut University Hospital, and 25 healthy controls were enrolled into the study (2016–2017). None of the patients was on systemic therapy, and they were off topical treatment for 3 months.

Those with diabetes mellitus, metabolic syndrome, infections, malignancies, autoimmune disorders, renal, hepatic, or cardiac diseases were excluded according to the history taken from patients. Participants gave their informed consent before enrollment and the study was approved by the Ethics Review Committee of Faculty of Medicine Assiut University [this work had been done in Assiut University Hospital after taking the ethics committee approval (IRB no: 17100820) (thesis for master’s degree)].

Height, weight, and waist circumference of patients and controls were recorded. Waist circumference was measured at the midpoint between the inferior borders of the rib cage and iliac crest [10]. The BMI was calculated as weight/height (kg/m2) and the participants were categorized into normal weight (18–25), overweight (>25–30), and obese (>30). Psoriasis severity was evaluated with the Psoriasis Area and Severity Index (PASI) and was categorized into mild (PASI <8), moderate (PASI 8–12), and severe (PASI >12) [11].

Venous blood samples were collected in the morning after a 12-h overnight fast. Serum was stored at −80 °C for later analysis. Serum PGRN levels (Sinogeneclon Com Ltd, PRC, Hangzhou, China) were determined using enzyme-linked immunosorbent assay kits according to manufacturer’s instruction.

Date entry and data analysis were done using SPSS version 19 (Statistical Package for the Social Sciences) (IBM SPSS Inc., Chicago, US). χ2 test was used to compare between qualitative variables. Independent samples t-test was used to compare quantitative variables between two groups. In case of nonparametric data, Mann–Whitney test was done to compare quantitative variables between two groups, and Kruskal–Wallis test for more than two groups. Spearman correlation was done to measure the correlation between quantitative variables. Multiple linear regression analysis was done to measure the risk factors. The P value was considered statistically significant when less than 0.05.


  Results Top


No statistically significant differences were detected between patients and controls as regards age, sex, waist circumference, and BMI. The mean±SD psoriasis duration was 13.4±10.21 years. The mean±SD PASI score was 14.94±7.00 ([Table 1]).
Table 1 Characteristics of the study participants

Click here to view


Serum PGRN level in patients with psoriasis was significantly higher than in controls (P<0.033) ([Table 1]). It was also significantly higher in patients with severe psoriasis than those with mild and moderate psoriasis (P<0.001) ([Figure 1]).
Figure 1 Serum progranulin in different levels of psoriasis.

Click here to view


Obese individuals in both patients and control groups showed a significantly higher serum PGRN level in comparison to those with normal and overweight (P<0.014 and 0.002, respectively).

Concentrations of serum PGRN showed positive correlation with PASI score, waist circumference, and BMI in psoriatic patients (P<0.001) ([Figure 2]). However, there was no statistically significant correlation between serum PGRN and duration of psoriasis (r=0.038, P=0.823).
Figure 2 Correlation between serum progranulin, Psoriasis Area and Severity Index score, BMI, and waist circumference.

Click here to view


Multiple linear regression analysis confirmed the independent association of serum PGRN with PASI scores (P>0.000).


  Discussion Top


In agreement with Haung et al. [7], we have shown that serum PGRN is elevated in patients with psoriasis compared with control. Moreover, we demonstrated that serum PGRN level was significantly increased in severe psoriasis and that it correlated positively with disease severity proposing PGRN as a marker of psoriasis severity.

The role of PGRN in psoriasis may be attributed to several hypothesis; first, its role in the maintenance and regulation of normal tissue proliferation, regeneration, and host defense response [12].

Second, PGRN is a strong anti-inflammatory mediator by being an antagonist of tumor necrosis factor-α (TNF-α) signaling. Previous studies have shown that PGRN is a high-affinity ligand of the TNF-α receptors 1 and 2 (TNFR1 and TNFR2) and that its anti-inflammatory effect is caused by direct inhibition of these receptors. PGRN directly binds to TNFRs and interferes with the interaction between TNF-α and TNFRs [13].

The third mechanism of action of PGRN in psoriasis was reported by Huang et al. [7], who reported that PGRN plays a protective role in the pathogenesis of psoriasis vulgaris partly by increasing the number of Treg cells. Their hypothesis is based on the fact that human skin is enriched in Treg cells − up to 80% of CD4+ T cells could be Treg cells in the skin of healthy individuals [14]. In contrast, patients with psoriasis have lower percentages of Treg cells in the affected skin. Moreover, studies of Treg cells in patients treated with infliximab [15], vitamin D3 [16], or 8-methoxypsoralen plus ultraviolet A [17] showed that increase in the numbers of Treg cells [18].

Finally, Farag et al. [19] reported a proinflammatory effect of PGRN in the pathogenesis of psoriasis mediated through decreasing β-catenin expression in psoriasis.PGRN also has proinflammatory role in obesity. We reported an increase of serum PGRN in obese patients compared with normal and overweight patients and moreover we found positive correlation between BMI and serum PGRN in both patients and controls. This is in agreement with Wu and Siegel [8] who found that circulating PGRN levels correlate with BMI, total body fat mass, and visceral fat area. They suggested that PGRN reflects chronic inflammation in obesity. It was also suggested that PGRN could be involved in the growth of adipose tissue; however, the exact role of PGRN in adipogenesis is not yet clear.

Given that obesity is part of the metabolic syndrome and that serum PGRN concentration was reported to be elevated in patients with metabolic syndrome, PGRN provides an important link between psoriasis and metabolic syndrome including cardiovascular morbidity [20].

In conclusion, the precise function of PGRN varies depending on the target tissue and the pathological setting of the disease. Serum PGRN could be a useful biomarker for psoriasis severity and adds further explanation to the association of psoriasis with obesity and metabolic syndrome.

Acknowledgements

The authors acknowledge the contributors in this study including the patients, paramedics, and the technicians for their general support through the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Tobin AM, Hackett C, Rogers S, Collins P, Richards HL, O’Shea D, Kirby B. The impact of obesity on psoriasis. Br J Dermatol 2011; 165 (S1):8–11.  Back to cited text no. 1
    
2.
Setty A, Curhan G, Choi H. Obesity, waist circumference, weight change, and the risk of psoriasis in Women Nurses’ Health Study II. Arch Intern Med 2007; 167:1670–1675.  Back to cited text no. 2
    
3.
Libby P, Okamoto Y, Rocha VZ, Folco E. Inflammationin atherosclerosis: transition from theory to practice. Circ J 2010; 74:213–220.  Back to cited text no. 3
    
4.
Ghazizadeh R, Shimizu H, Tosa M, Ghazizadeh M. Pathogenic mechanisms shared between psoriasis and cardiovascular disease. Int J Med Sci 2010; 7:284–289.  Back to cited text no. 4
    
5.
Woelnerhanssen B, Peterli R, Steinert RE, Woelnerhanssen B, Peters T, Christoffel-Courtin C et al. Effects of post bariatric surgery weight loss on adipokines and metabolic parameters: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy − a prospective randomized trial. Surg Obes Relat Dis 2011; 7:561–568.  Back to cited text no. 5
    
6.
Coimbra S, Santos-Silva A. Biomarkers of psoriasis severity and therapy monitoring. World J Dermatol 2014; 3:15–27.  Back to cited text no. 6
    
7.
Huang K, Chen A, Zhang X, Song Z, Xu H, Cao J, Yin Y. Progranulin is preferentially expressed in patients with psoriasis vulgaris and protects mice from psoriasis-like skin inflammation. Immunology 2015; 145:279–287.  Back to cited text no. 7
    
8.
Wu H, Siegel RM. Progranulin resolves inflammation. Science 2011; 332:427–428.  Back to cited text no. 8
    
9.
Liu CJ. Progranulin: a promising therapeutic target for rheumatoid arthritis. FEBS Lett 2011; 585:3675–3680.  Back to cited text no. 9
    
10.
Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA et al. Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; American heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation 2009; 120:1640–1645.  Back to cited text no. 10
    
11.
Fredriksson T, Pettersson U. Severe psoriasis—oral therapy with a new retinoid. Dermatologica 1978; 157:238–244.  Back to cited text no. 11
    
12.
Jian J, Konopka J, Liu C. Insights into the role of progranulin in immunity, infection, and inflammation. J Leukoc Biol 2013; 93:199–208.  Back to cited text no. 12
    
13.
Tang W, Lu Y, Tian QY, Zhang Y, Guo FJ, Liu GY et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 2011; 332:478–484.  Back to cited text no. 13
    
14.
Antiga E, Quaglino P, Bellandi S, Volpi W, Del Bianco E, Comessatti A et al. Regulatory T cells in the skin lesions and blood of patients with systemic sclerosis and morphoea. Br J Dermatol 2010; 162:1056–1063.  Back to cited text no. 14
    
15.
Quaglino P, Ortoncelli M, Comessatti A, Ponti R, Novelli M, Bergallo M et al. Circulating CD4+ CD25brightFOXP3+ T cells are up-regulated by biological therapies and correlate with the clinical response in psoriasis patients. Dermatology 2009; 219:250–258.  Back to cited text no. 15
    
16.
Van der Aar AM, Sibiryak DS, Bakdash G, van Capel TM, van der Kleij HP, Opstelten DJ et al. Vitamin D3 targets epidermal and dermal dendritic cells for induction of distinct regulatory T cells. J Allerg Clin Immunol 2011; 127:1532–1540.  Back to cited text no. 16
    
17.
Singh TP, Schön MP, Wallbrecht K, Michaelis K, Rinner B, Mayer G et al. 8-methoxypsoralen plus ultraviolet A therapy acts via inhibition of the IL-23/Th17 axis and induction of Foxp3+ regulatory T cells involving CTLA4 signaling in a psoriasis-like skin disorder. J Immunol 2010; 184:7257–7267.  Back to cited text no. 17
    
18.
Zhao YP, Tian QY, Liu CJ. Progranulin deficiency exaggerates, whereas progranulin-derived Atsttrin attenuates, severity of dermatitis in mice. FEBS Lett 2013; 587:1805–1810.  Back to cited text no. 18
    
19.
Farag A, Shoaib M, Samaka R, Mandour M, Ibrahim R. Progranulin and beta-catenin in psoriasis: an immunohistochemical study. J Cosmet Dermatol 2019; 18:2019–2026.  Back to cited text no. 19
    
20.
Li H, Zhou B, Xu L, Liu J, Zang W, Wu S, Sun H. Circulating PGRN is significantly associated with systemic insulin sensitivity and autophagic activity in metabolic syndrome. Endocrinology 2014; 155: 3493–3507.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
   Abstract
  Introduction
  Patients and methods
  Results
  Discussion
   References
   Article Figures
   Article Tables

 Article Access Statistics
    Viewed161    
    Printed12    
    Emailed0    
    PDF Downloaded31    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]