Serum clusterin in psoriasis: relation to metabolic syndrome

INTRODUCTION

Psoriasis is a common long standing immune-related disease that affects 1% - 3% of the general people and is characterized by inflammation and hyperproliferation of epidermal cells.^1,2However, it has been known to be a systemic disorder related to metabolic syndrome including obesity, insulin resistance, hypertension and atherogenic dyslipidemia.³ The intensity of inflammation and skin changes in psoriasis may not only indicate the severity of psoriasis but also that of other systemic pathologies.⁴

Psoriasis patients had higher rates of insulin resistance, hypertension, dyslipidemia, and obesity which are risk factors for further cardio-vascular problems.¹ There are higher morbidity and mortality rates in psoriatic patients with atherosclerosis and cardiovascular diseases.⁴  previous studies found that there was no increased mortality rate for outpatient psoriatic patients, but there was an increased mortality rate from cardiovascular diseases among hospitalized psoriatic patients.^5,6

Clusterin "apolipoprotein J" is a disulfide glycoprotein with its code at chromosome 8 which called the CLU gene. It shares in the antiapoptotic process, so plays a role in neurodegenerative disorders, inflammation and tumors.⁷ CLU plays an important role in metabolic disorders linked with inflammation and oxidative stress such as diabetes, obesity, atherosclerosis and insulin resistance.^8,9

Clusterin is a protein element of high-density lipoproteins. It had a protective role in myocarditis and athero-sclerosis. It could be considered as an inhibitor of future coronary events ¹⁶. But recently Zhu et el. found that clusterin increased in patients with early coronary artery diseases.¹⁵

Buquicchio et al. found that clusterin is elevated in psoriatic patients having comorbidites like metabolic syndrome and cardiovascular diseases, and suggested further studies to strengthen the value of serum levels of clusterin / apo J and to suggest its use as a new marker in psoriasis.¹⁰ Garcia- Rodriguez et al. observed that plasma clusterin was reduced in psoriasis patients compared with healthy controls but the study had a small sample size.¹⁴ while, Ataseven et al. reported that there was no difference in clusterin levels among psoriatic patients and controls.¹²

The aim of this work to define the level of clusterin among psoriatic patients in comparison to normal controls, to compare clusterin levels in psoriatic patients having and not having metabolic syndrome and to define the role of clusterin levels in disease severity.

PATIENT AND MATERIALS

This study is a case-control study. It was done on 60 psoriatic patients and 30 sex- and age-matched healthy people. They were enrolled from Dermatology Outpatient Clinic at El-Hussein University Hospital and Kobry Al-Kobba Military Hospital in the period from 1/1/2019 to 15/9/2019.

All psoriasis patients have severe psoriasis vulgaris with PASI > 10. On the other hand, patients with other types of psoriasis (other than vulgaris), mild psoriasis (PASI < 10) and known cardiac patients were excluded.

Patients with metabolic syndrome had at least 3 of the following: Serum triglycerides 150 mg/dl or above, abdominal obesity with a waist circumference of 102 cm or more in males and 88 cm or more in females, HDL cholesterol 40 mg/dl or lower in males and 50 mg/dl or lower in females, Fasting blood glucose of 100 mg/dl or above and Blood pressure of 130/85 or more.

All subjects signed consent to participate in this work after an explanation of the steps of the study. The study was accepted by research ethical committee at Al-Azhar University and fulfilled all the ethical aspects required in human research.

The study had 30 patients had psoriasis only (group B) and 30 patients had psoriasis and metabolic syndrome (group A) and 30 sex and age-matched healthy people (group C).

All patients undergone full History taking [personal history, present illness, family history, other dermatological or systemic diseases, and previous therapy]. written consent was signed by each participant before initiation of the study.

In addition, all patients were subjected to general examination and PASI scoring which estimates the disease severity in relation to three parameters including redness [R], thickness [infiltration] [T] and scaling [desquamation] [S].¹¹

Venous blood sample (3 ml) was collected from psoriatic patients and controls and left to clot for 20 minutes at ordinary temperature. The sample was centrifuged at a speed of 2000 - 3000 r.p.m for 20 minutes, and serum was taken and left at -20˚C till assayed.

Routine investigations were done as CBC, FBS, 2 hpp blood sugar, total cholesterol, triglyceride, LDL and HDL.

Serum clusterin was determined by a commercially available ELISA kit manufactured at Shanghai Korain Biotech Company, Shanghai, China; kit’s no is E1189Hu with package size of 96T per box and assay range 1-300ng/ml. This kit uses enzyme-linked immune sorbent assay (ELISA) depending on the Biotin double antibody sandwich technology for assayment of the Human Clusterin (CLU). Add the sample to the wells, which are pre-covered with Clusterin (CLU) monoclonal antibody and incubate. Later on, combine anti CLU antibodies asorted with biotin to gather with streptavidin-HRP forming an immune complex. Remove ungathered enzymes after washing. Combine substrate A and B. Then the solution will turn blue and change into yellow affected by acid. The shades of the solution and the concentration of Human Clusterin (CLU) are correlated positively.

Statistics: Descriptive statistics were calculated for the data in the form of Mean and standard deviation (SD) for quantitative data and Frequency and distribution for qualitative data. In the statistical comparison between different groups, the significance of difference was tested using one of the following tests:  Student's t-test, ANOVA test (F value), chi-square test (X²-value), fisher exact test (FET) or Correlation coefficient. A P -value0.05 insignificant P-value

RESULTS

The present study was conducted on 60 psoriasis patients and 30 persons as controls. Their mean age was 34.28 years, they were 80 males [88.9 %] and 10 females [11.1 %], mean height was 167.01, mean weight 75.94, mean BMI 27.46 and mean waist circumference 92.48. (Table 1)

The 60 patients were divided into 30 psoriasis patients with metabolic syndrome group (A) with mean PASI 12.336, mean duration 6.97, mean clusterin level 89.55 and most of them had gradual onset 90% and 30 psoriatic patients without metabolic syndrome group (B) with mean PASI 12.836, mean duration 5.75, mean clusterin level 105.88 and most of them had gradual onset 80%. The controls had mean clusterin level of 95.53. (Table 2)

        No significant differences were found in serum clusterin level according to other studied parameters in all studied cases. (Table 3)

        No significant correlation was found in clusterin level among all patients and controls. (Table 4)

        No significant correlation was found in clusterin level among patients having metabolic syndrome and controls. (Table 5)

        No significant correlation was found in clusterin level among patients without metabolic syndrome and controls. (Table 6)

        No significant correlation was found in clusterin level among patients who have and have no metabolic syndrome. (Table 7)

Table 1: Distribution of the studied groups according to personal data.

Table 2: Comparison between the studied groups according to clinical data and clusterin levels.

Table 3: Correlation of Clusterin level with other studied parameters in patients and controls.

Table 4: Comparison of Clusterin concentration between all psoriasis patients and controls.

Table 5: comparison of clusterin concentration between patients having metabolic syndrome and controls.

Table 6: comparison of clusterin concentration between patients without metabolic syndrome and controls.

Table 7: comparison of clusterin concentration between patients having and not having metabolic syndrome.