Irisin Level in the Serum of Patients with Psoriasis and its Correlation with Adiponectin Level and the Clinical Severity
Aisha Hamza Gamil1, Mahmoud Yousry Abdel-Mawla1,Naglaa Ali Khalifa2, Mohamed Mahmoud Nasr1
1Dermatology, Venereology and Andrology Department, Faculty of Medicine, Zagazig University, Egypt
2 Clinical Pathology Departments, Faculty of Medicine, Zagazig University, Egypt Abstract
Background: Psoriasis is a common chronic immune mediated papulosquamous disease that affects 2-3% of the population. The exact cause of psoriasis is still unclear, but it is considered a disease of dysregulated inflammation. Irisin is a novel myokine which is induced by exercise. It is considered as an acute phase protein and marker of inflammation in psoriasis, as irisin level positively correlated with c reactive protein (CRP) levels and sedimentation rate (SR) in psoriatic patients.The aim of this work was to estimate the serum level of Irisin by ELISA and detect its correlation with thepsoriatic activity.Methods: the study was carried outon one hundred subjects divided into two groups: groupI included 50 psoriatic patients and group II included 50 healthy subjects. All patients were subjected to the followings: full medical history, complete general examination, and Proper dermatologic examination.Psoriasis severity was classified according to psoriatic area and severity index (PASI) score. Serum level of irisin was determined by ELISA for both groups.Results: the results revealed that the psoriasis group had significantly higher level of irisin than the control group and there was a significant positive correlation with PASI score (p 0.002*). The sensitivity of irisin in diagnosis of psoriasis was 84%, specificity was 44%
and accuracy was 64%. Conclusion:Irisin measurement in the serum of patients with psoriasis provides a tool for monitoring disease activity and can be used as a marker forpsoriasis severity.
Keywords:Irisin, Psoriasis, Myokine, PASI, Marker Introduction
Psoriasis is a chronic, hyperproliferative inflammatory disease of the skin, which is clinically characterized by erythematous and squamous plaques. The disease is associated with a genetic background [1]. Psoriasis is mediated by a crosstalk between epidermal keratinocytes, dermal vascular cells, and immunocytes such as (APCs) and T cells [2]. Patients with psoriasis are at a higher risk of numerous comorbidities such as obesity, cardiovascular disease, metabolic syndrome or insulin resistance and diabetes mellitus [3]. Irisin is a myokine produced by skeletal muscle after physical exercise, and originally described as a molecule able to promote the browning of white adipose tissue [4]. There is a strong association between psoriasis and insulin resistance, suggesting a possible role for irisin in etiopathogenesis of psoriasis, as irisin is known to reduce weight by increasing total energy expenditure, and decrease insulin resistance caused by diet [5].Irisin also plays a role in immunity as it has anti –inflammatory properties by suppression of expression of pro-inflammatory cytokines, (NF-kB), tumor necrosis factor (TNF), IL-6 and inducing the phenotypic switching of adipose tissue macrophages from M1 (pro- inflammatory) to M2 (anti-inflammatory) state[6]. Cytokines such as TNF α has important roles in the pathogenesis of psoriasis. These cytokines reduce the release of irisin from skeletal muscle and signaling pathways leading to psoriasis development [7].The reported circulating levels of
irisin in human serum or plasma have been ranged between 0.01ng/ml and 2,000ng/ml [8]. Irisin levels are increased in obese subjects and could be used as a biomarker for poor or altered metabolic status in obese patients [9, 10].There is a significantly higher prevalence of metabolic syndrome in psoriatic patients ranging from 40% to 65% [11]. Irisin is not only a myokine but also adipokine with its auto- and paracrine actions [12].It could be used as an indicator of body fat mass as it was elevated in obese subjects in many studies. However, it could be only a compensatory mechanism [13]. Surprisingly,a positive relationship between serum irisin and PASI has been detected. Irisin might be a marker of inflammation in psoriatic patients, but may not be a reliable indicator of metabolic conditions;neither severity of psoriasis nor efficacy of antipsoriatic treatment [14].This may underlines considering irisin as an acute phase protein and a marker of inflammation in psoriasis. In this study, we sought to assess serum levels of irisin in patients with psoriasis and the relationship of irisin to psoriasis activity and severity.
Subjects and Methods
Subjects:This case control study was carried out at the outpatient clinic of Dermatology, Venereology and Andrology Department at Faculty of Medicine, Zagazig University Hospitals, during the period from November 2019 to November 2020.One hundred individuals of both sexes and different ages participated in this study. They were divided into Group I: 50 psoriatic patients, 33 males and 17 females. Their age ranged from 18 to 65 years. Group II: 50 healthy individuals, 24 male and 26 females.Their age ranged from 18 to 65 years. Demographic characteristics of the patients at the beginning of the study are illustrated in Table (1). Inclusion criteria included patients of both sexes with psoriasis vulgaris. Exclusion criteria included patients who had received any systemic treatment or ultraviolet therapy for psoriasis in the prior 6 months, the presence of any systemic disease and those younger than 18 years of age.
History taking and clinical examination:All patients and the control group were subjected to the following: Detailed history taking which included personal history, history of associated other dermatological or systemic diseases, history of drug intake and family history. General examination of body systems was performed to discover associated medical conditions including pulse, blood pressure and joint examination. Also, body mass index (BMI) was evaluated for both groups [15].
Detailed dermatological examination: Complete dermatological examination was done involving skin, hair, mucous membranes and nails. The severity of Psoriasis was assessed by the Psoriasis Area and Severity Index (PASI score) as follow: The body was divided into four sections (head (H) (10% of a person's skin); arms (A) (20%); trunk (T) (30%); legs (L) (40%)).
Each of these areas is scored separately, and then the four scores are combined into the final PASI. For each section, the percent of area of skin involved, is estimated and then transformed into a grade from 0 to 6 as previously described. Within each area, the severity was estimated by three clinical signs: erythema (redness) E, induration (thickness) I and desquamation (scaling) D.
Severity parameters were measured on a scale of 0 to 4, from none to very severe. Finally, the sum of all three severity parameters was then calculated for each section of skin, multiplied by the area score for that area and multiplied by weight of respective section (0.1 for head, 0.2 for arms, 0.3 for body and 0.4 for legs) [16].
Measurement of serum level of Irisin:Serum level of irisin was measured by enzyme linked
instructions, 50 μl of standard and 50 μl of streptavidin –HRP were added to the standard wells.
In the test wells: 40 μl of sample, 10 μl of irisin- antibodies and 50 μl of streptavidin –HRP were added. Then we sealed the sealing membrane, gently shacked and incubated 60 minutes at 37°C.
After that, washing was done carefully and then chromogen solutions A,B were added to each well. Mixing and incubation for 10 min at 37°C away from light was done. Finally, 50 μl of stop solution was added into each well to stop the reaction (the blue changed to yellow immediately) and the optical density (OD) was measured [17].
Ethical Considerations: This work has been carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for studies involving humans.
Written informed consents were obtained from the study participants. Approval by IRB research committee of Zagazig Faculty of Medicine was also included.
Statistical analysis
After the data collection, the data was analyzed by statistical package of SPSS-19 (SPSS, Inc., Chicago, IL, USA) and the following tests were used: Chi–square (X2), Student t-test, Spearman's correlation coefficient (r), and One way ANOVA [18]. Differences were consideredstatistically significant (S) when (P< 0.05) and non-significant (NS) when (P> 0.05).
A receiver operating characteristic (ROC) curve analysis was conducted to evaluate the performance of Irisin assay for the prediction of active psoriasis disease. The sensitivity (true positive rate), specificity (true negative rate), is estimated and confidence interval (CI) of 95%, were obtained for each study and subsequently combined. The statistical analysis was based on the intention-to-treat population. Data was represented as mean ± SD, range, numbers or percentages.
Results
There were no statistically significant differences between the psoriasis groupand the control groupregarding age, sex distribution or obesity as can be detected in table (1). The duration of psoriasis among the studied psoriasis group ranged from 1 to 20 years with mean 6.16 years.
Regarding family history only 4% had positive family history of psoriasis.Table (2) shows that the PASI score of psoriasis among the studied psoriasis group ranged from 0.8 to 23.8 with mean 10.62. All cases had erthyma, induation and scale. Regarding MS (metabolic syndromes) (Diabetes, Hypertension) it was founded in 38% of the cases. The severity of cases according to PASI score was as follow: 48% of patients were mild, 40% were moderate & 12% were sever.
There was a significant increase in thelevel of Irisin in Group I compared to Group II (P= 0.001) as can be observed in table (3) with mean 1.82 ± 0.92 and 1.23 ± 0.63 respectively. In table (4), there was no statistically significantcorrelation between sex, obesity, family history, metabolic syndrome (MS) and irisin level among the psoriasis group. There was a significant positive correlation between PASI score and irisin among psoriasis group (r=0.42, p=0.002*) as in Figure (1).Mean adiponectin serum level for group I was 0.53 ± 0.33 and for group IIwas 3.39 ± 3.57 in our unpublished data and we found that there was a negative significant correlation between adiponectin and irisin among psoriasis patients (r=-0.41, p=0.003*) as can be seen in Figure (2).
Figure (3) demonstrates thatthe sensitivity of irisin in diagnosis of psoriasis at cut off >1.15 ng/ml was 84%, the specificity was 44% and the accuracy was 64%.
Table (1): Demographic data of the studied groups SD:
Standard deviation t: Independent t test χ2: Chi square test NS: Non significant (P>0.05) BMI: body mass index
Table (2): Clinical data of the psoriasis group Variable
Group I (Psoriasis)
(n=50) PASI:
Mean ± Sd Median
Range
10.62 ± 5.84 10.8 0.8 – 23.8
Variable No %
Erthyma: No
Yes
0 50
0 100
Induration: No
Yes
0 50
0 100
Scale: No
Yes
0 50
0 100 MS:
Diabetes, Hypertension
No Yes
31 19
62 38 Severity:
Mild (<10) Moderate (10-<20)
Sever (≥20)
24 20 6
48 40 12 SD: Standard deviation
Table (3):Irisin level among the studied groups Variable
Group I (Psoriasis)
(n=50)
Group II (Control) (n=50)
T P
Age: (years) Mean ± Sd Range
39.74 ± 13.09 19 - 64
35.94 ± 7.96
20 – 50 1.75 0.08 NS
Variable No % No % χ2 P
Sex:
Female
Male 17
33
34 66
26 24
52
48 3.31 0.07 NS Obesity:
(BMI)
No Yes
32 18
64 36
29 21
58
42 0.38 0.54 NS
Range 1 – 5.4 0.1 – 2.2 SD: Standard deviation MW: Mann Whitney
*: Significant (p<0.05) **: Highly significant (P<0.001)
Table (4): Relationship between Irisin& some parameters of the psoriasis group
Variable No Irisin (ng/ml)
MW P
Mean±SD Median Range
Sex Female
Male
17 33
1.75±0.48 1.85±1.08
1.9 1.6
1 – 2.3
1 – 5.4 0.92 0.35 NS
Obesity No
Yes
32 18
1.67±0.57 2.07±1.31
1.4 2
1 – 3.2
1 – 5.4 0.41 0.68 NS Family
history:
-ve +ve
48 2
1.83±0.93 1.60±0.2
1.6 1.6
1 – 5.4
1.5 –1.7 0.01 0.99 NS
MS: No
Yes
31 19
1.68±0.61 2.04±1.26
1.6 2
1 – 3.2
1 – 5.4 0.45 0.65 NS SD: Standard deviation MW: Mann Whitney test
NS: Non significant (P>0.05) Ms: metabolic syndrome
Figure (1): Correlation between PASI & Serum irisin level among Group I.
Figure (2): Correlation between serum adiponectin versus serum irisin among Group I.
Discussion
Irisinis a novel myokine produced by skeletal muscle in response to physical activity.It promotes white-to-brown fat trans differentiationwhich known as fat browning, and enhances expression of themuscular (PGC-1a) which increases thermogenesis and energy expenditure [19]. It is considered as an acute phase protein and marker of inflammation in psoriasis, as irisin level positively correlated with CRP levels and ESR in psoriatic patients [14].The purpose of the present study was to identify if there was any relationship between the serum level of Irisin and severity of psoriasis.
This study revealed that psoriasis was more prevalent in male than female that is similar to the results obtained by Bai, et al., (2018) [20]. As regard obesity, there was no a statistically significant difference between the two groups which are consistent with those reported by Oh, et al., (2014) [21]. In contrast to our findings, the study of Murray et al., (2009) confirmed the positive association between BMI and psoriasis severity [22]. This difference may be due to the large number of patients included in their study and the different demography (South‐western).
Concerning the duration, it is evident that the duration of psoriasis ranged from 1 to 20 years which is different from the study of Baran, et al., (2015) which reported that disease duration varied from 7 months to 55 years [23]. In our study only 4% of patients had +ve family history of psoriasis, while Oh, et al. who studied Korean patients found that 29.2 % of patients showed positive family history of psoriasis [21]. Our results reported that 38% of the cases have metabolic syndrome. Bavoso, et al., (2019) found that DM was detected in19.5% of the cases and in 2.4% of the controls which was dissimilar to our findings [24].
Our results revealed that the psoriasis group had significantly higher level of irisin than the control group.These results are nearly similar to those reported by Baran et al., (2017) who studied Poland patients and found that serum Irisin level was increased in psoriatic patients in comparison to the controls [14]. A Turkish study of Alatas, et al., (2017) mentioned that Serum irisin and salivary irisin levels were significantly lower in the patient group compared with the control group. In the patient group was 257.12±67.33ng/ml, while in control group was 292.39±31.81ng/ml, which does not support our results [25]. This may be clarified as follow:
most of our patients were farmers with increased muscular activity which is one of the causes of irisin elevation. We founda positive relationship between PASI and irisin in the present study.
This was similar to what had been mentioned by Bulur, et al., (2018), as they found that The PASI scores and serum irisin levels were positively correlated [26]. In contrast to our study, Alatas, et al., (2017) showed that there was a negative correlation between PASI score and irisin, as the irisin level was low in the serum of their patients [25]. This may be due to the small number of subjects in their study. Moreover,Baran et al., (2017) study was unlike our one, in which serum irisin level did not correlate with the PASI score [14].In the present study, there was no a statistically significant relation between sex,obesity, family history, metabolic syndromes and irisin level among psoriasis group. On the other hand there were significant correlations between serum irisin level and age or disease duration reported by Baran et al., (2017) [14].
To the best of our knowledge, investigating serum adiponectin and serum irisin with each other has never been previously tried. We found that there was a negative significant correlation between adiponectin and irisin among psoriasis patients. It is appearing that sensitivity of irisin in diagnosis of psoriasis was 84% so irisin needs more investigations with increased number of patients, large geographical scale and comparison with other biomarkers.
Conclusion
In conclusion, serum irisin might be a new biomarker for prediction and evaluation of psoriasis severity as they are closely connected with the inflammatory states in psoriasis and correlated with the clinical state. It is also sensitive and specific in the diagnosis of psoriasis. Serum irisin might be a useful marker for assessment of the treatment and clinical follow-up of psoriasis patients. Further studies of irisin are required with large-sample population to identify its association with psoriasis.
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