|Year : 2017 | Volume
| Issue : 1 | Page : 11-14
Level of serum soluble endothelial leukocyte adhesion molecule-1 in psoriatic patients after narrow-band ultraviolet-B and relation to disease activity: a case–control study
Nazeha H Khafagy1, Ghada Fathy1, Ayman H Khafagy1, Mohamed S Mostafa2, Eman M.A. Mostafa1
1 Department of Dermatology, Venereology, and Andrology, Ain Shams University, Cairo, Egypt
2 Poison Control Center, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Submission||10-Jul-2016|
|Date of Acceptance||17-Nov-2016|
|Date of Web Publication||2-Jun-2017|
7 El-Menya Street, Heliopolis, Cairo, 11341
Source of Support: None, Conflict of Interest: None
Endothelial leukocyte adhesion molecule-1 (E-selectin) is expressed on endothelial cells in psoriasis vulgaris (PV). Alteration in E-selectin is one of the influential proinflammatory cytokines in the pathogenesis of psoriasis.
This study aimed to assess the serum level of E-selectin and to determine the effect of narrow-band ultraviolet-B (UVB) therapy on serum E-selectin levels in patients with psoriasis and to assess the relationship between serum E-selectin levels and disease activity after this treatment.
Settings and design
This was a case–control study.
Patients and methods
Thirty-five patients with chronic plaque psoriasis and 35 age-matched and sex-matched healthy controls were included. The concentration of soluble E-selectin (sE-selectin), determined by enzyme-linked immunosorbent assay was studied in the sera of patients before and after narrow-band UVB treatment sessions (three times per week for 3 months) and compared with normal nonpsoriatic controls. The disease severity was established using the Psoriasis Area and Severity Index scoring system.
Levels of sE-selectin were significantly increased in the sera of patients with atopic dermatitis and psoriasis (compared with the controls). Clinical improvement, after treatment, in patients with PV was associated with a significant decrease in the serum levels of sE-selectin. There was a significant correlation of sE-selectin and disease activity in PV patients.
E-selectin might be an indicator of treatment response and acts as a marker of psoriatic disease activity; it is also suggested to be a useful tool for evaluating the efficacy of treatment by narrow-band UVB in patients with psoriasis.
Keywords: narrow-band ultraviolet-B, psoriasis vulgaris, soluble E-selectin
|How to cite this article:|
Khafagy NH, Fathy G, Khafagy AH, Mostafa MS, Mostafa EM. Level of serum soluble endothelial leukocyte adhesion molecule-1 in psoriatic patients after narrow-band ultraviolet-B and relation to disease activity: a case–control study. Egypt J Dermatol Venerol 2017;37:11-4
|How to cite this URL:|
Khafagy NH, Fathy G, Khafagy AH, Mostafa MS, Mostafa EM. Level of serum soluble endothelial leukocyte adhesion molecule-1 in psoriatic patients after narrow-band ultraviolet-B and relation to disease activity: a case–control study. Egypt J Dermatol Venerol [serial online] 2017 [cited 2017 Jun 26];37:11-4. Available from: http://www.ejdv.eg.net/text.asp?2017/37/1/11/207486
| Introduction|| |
E-selectin is a cell adhesion molecule-1 of the vascular endothelium that promotes essential leukocyte rolling in the early inflammatory response. It is expressed on endothelial cells and mediates the adhesion between activated endothelium and different inflammatory cells .
Psoriatic plaques are characterized by strong E-selectin expression on the luminal surfaces of the capillary and the postcapillary endothelial cells . Soluble cell adhesion molecules, including soluble E-selectin, may serve as markers for CAMs and represent important biomarkers for inflammatory processes involving activation of or damage to cells such as platelets and the endothelium .
Memory T lymphocytes play an important role in the pathogenesis of psoriasis by interacting with the vascular E-selectin and trafficking into lesional skin. Tumor necrosis factor α (TNF-α) released by T cells is one of the most potent proinflammatory cytokines prevalent in psoriatic lesions. TNF-α exerts many effects in the induction of an inflammatory response such as stimulating the production of proinflammatory chemokine and adhesion molecules (e.g. soluble E-selectin, soluble P-selectin, and soluble intracellular adhesion molecule-1). These play a major role in cutaneous inflammatory events by directing leukocyte trafficking and also by their impact on antigen presentation. Skin biopsies obtained from psoriatic lesions showed upregulation of endothelial cell expression of E-selectin .
Lesional psoriatic skin already contains a variety of immune competent cells, and it is most likely that a combination of depletion and altered function of these cells is the key to the effectiveness of ultraviolet-B (UVB) light therapy for psoriasis .
Narrow-band (NB) UVB has been reported to induce the infiltration of leukocytes into normal skin and these cells produce IL-10 , which in turn inhibits the expression of cutaneous leukocyte antigens and other adhesion molecules such as E-selectin, which would inhibit the infiltration of T cells to the skin .
These data highlight a pivotal role of E-selectin in the pathogenesis of psoriasis; thus, the aim of this work was to assess the serum level of E-selectin, to determine the effect of NB-UVB therapy on serum E-selectin levels in patients with psoriasis, and to assess the relationship between serum E-selectin levels and disease activity after this treatment.
| Patients and methods|| |
This case–control study was carried out on patients with moderate to severe chronic plaque-type psoriasis. The patients were recruited from the Outpatient Clinic of Dermatology. Thirty-five patients with chronic plaque psoriasis and 35 age-matched and sex-matched healthy control participants were enrolled in this study. All participants provided written consent to participate in this study after an explanation of the steps of the study was provided. The study was approved by the research ethical committee of the institution according to the Helsinki Declaration. Patients aged 20–65 years, and no sex predilection, with moderate to severe chronic plaque-type psoriasis [Psoriasis Area and Severity Index (PASI) score >10] were included . Patients who had received treatment (systemic or topical) for psoriasis during the last 6 months or patients with photosensitivity, photodermatoses, or skin cancers were excluded.
Measurements of the level of E-selectin were performed at the initial visit and at the end of the study for all participants (patients and controls). Venous blood samples were obtained for the determination of serum E-selectin using enzyme-linked immunosorbent assay (ELISA) technology. Aviva’s human E-Selectin ELISA kit (Orgenium, Vantaa, Finland) was based on the standard sandwich ELISA technology. Human E-selectin-specific polyclonal antibodies were precoated onto 96-well plates.
The psoriatic patients were administered treatment by NB-UVB therapy (three times a week for 3 months) (Waldmann UV 2007, TL01; Waldmann, Villingen-Schwenningen, Germany). The emission maximum irradiation was 311 nm.
Data analysis was carried out using the statistical package for the social sciences (SPSS) software (version 18; IBM Corporation, Armonk, New York, USA). Quantitative data were expressed as mean±SD. Qualitative data were expressed as frequency and percentage. The Student t-test was used. Differences between categorical variables were analyzed using χ2-test, with the Fisher’s test applied when appropriate. Pearson’s correlation coefficient (r) test was used to correlate data. Positive and negative predictive values were determined. A P-value of less than 0.05 was considered statistically significant.
| Results|| |
The age of the patients ranged from 23 to 62 years, with a mean age of 42.46±11.80 years, whereas among the control participants, the age ranged from 27 to 51 years, with a mean age of 38.20±7.90 years; there was no statistically significant difference in the mean age between patients and controls (P=0.08). In terms of the sex distribution, among the patients, 65.7% (n=23) were men and 34.3% (n=12) were women, and among the control participants, 68.6% (n=24) were men and 31.4% (n=11) were women. There was no statistically significant difference between the patients and the controls in terms of sex (P=0.799).
Before NB-UVB therapy, the level of serum E-selectin in patients ranged from 91.8 to 150.8 ng/ml (mean: 121.15±19.88 ng/ml) and that in controls ranged from 33.4 to 57 ng/ml (mean: 43.35±7.61 ng/ml). Comparisons of the mean values of serum E-selectin level between cases and controls showed a highly significant difference (121.15±19.88 and 43.35±7.61, respectively; P<0.01).
After NB-UVB therapy, the level of serum E-selectin ranged from 51 to 103.4 ng/ml (mean: 76.96±16.55 ng/ml). There was a statistically significant difference on comparing serum E-selectin in patients before and after treatment with NB-UVB (121.15±19.88 and 76.96±16.55, respectively; P<0.001) ([Table 1]).
|Table 1: Changes in E-selectin before and after narrow-band ultraviolet-B treatment in the patient group|
Click here to view
Before NB-UVB therapy, the range of the PASI score was 20.3–50.0 (mean: 32.82±8.44) and after treatment, at the end of the study, the range of the PASI score was 5.0–17.3 (mean: 10.83±3.21). Comparison showed a statistically significant difference (P<0.001). Correlation of serum E-selectin with the PASI score before NB-UVB treatment showed that there was a highly significant positive correlation (r=0.660, P<0.001) ([Figure 1]). Correlation of serum E-selectin with the PASI score after NB-UVB treatment showed that there was a highly significant positive correlation (r=0.599, P<0.001) ([Figure 2]).
|Figure 1: Positive correlation of serum E-selectin with the Psoriasis Area and Severity Index (PASI) score: before narrow-band ultraviolet-B treatment|
Click here to view
|Figure 2: Positive correlation of serum E-selectin with the Psoriasis Area and Severity Index (PASI) score: after narrow-band ultraviolet-B treatment|
Click here to view
| Discussion|| |
In this case–control study, our findings further provide evidence that E-selectin is increased in psoriasis. Participants with psoriasis had significantly higher means of serum E-selectin concentrations than those without psoriasis. We found an association of high serum E-selectin levels with psoriasis. There was a significant decrease in serum E-selectin in patients on comparing before versus after treatment with NB-UVB. Lower serum E-selectin levels were associated with more severe disease. Serum E-selectin levels were correlated positively with PASI scores before and after treatment. Levels of E-selectin were not affected by age or sex, indicating that neither age nor sex has an influence on E-selectin function as a soluble cell adhesion molecule.
Our findings are in agreement with those of other coworkers who have established associations between high serum E-selectin level and psoriasis, and increased pretreatment serum E-selectin levels in psoriatic patients in comparison with healthy controls, which further supports the suggestions that alterations of E-selectin might be one of the influential proinflammatory cytokines in the pathogenesis of psoriasis ,,.
Serum E-selectin levels decreased significantly after NB-UVB therapy at the end of the study in comparison with pretreatment levels; these results were in agreement with previous studies that investigated the influence of treatment on serum E-selectin levels ,,,,. NB-UVB therapy reduced PASI score by more than 75%, as reported in previous reports ,. The reduction of serum E-selectin after treatment may be because of the induction of apoptosis in T cells  or because of the downregulation of T-cell adhesion molecules, which disrupts the T-cell activation . Another reason for the reduced E-selectin levels could be the effects of treatment on TNF-α levels, which activates endothelial cells and induces E-selectin or endothelial leukocyte adhesion molecule .
Therefore, our results point out that E-selectin might be an indicator of treatment response and acts as a marker of psoriatic disease activity and is suggested to be a useful tool for evaluating the efficacy of treatment by NB-UVB in patients with psoriasis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Preston RC, Jakob RP, Binder FPC, Sager CP. E-selectin ligand complexes adopt an extended high affinity conformation. J Mol Cell Biol 2016; 8:62–72.
Ataseven H, Ozturk P, Ozdemir M, Kesli R. Levels of serum soluble P-selectin and E-selectin in psoriatic patients. J Ann Dermatol. 2014; 26:275–277.
Sorour EN, Saleha AA, Sabry HJ. The effect of narrow-band ultraviolet-B phototherapy on soluble intercellular adhesion molecule-1 and soluble E-selectin in psoriasis vulgaris patients. Egypt J Dermatol Venereol 2014; 34:10–14.
Ghalamkarpour F, Saeedi M, Hedayati M. Soluble E-selectin and P-selectin serum levels in patients with psoriasis compared to healthy controls. Iran J Dermatol 2010; 13:9–11.
Kang K, Hammerberg C, Meunier L, Cooper KD. CD11b+ macrophages that infiltrate human epidermis after in vivo ultraviolet exposure potently produce IL-10 and represent the major secretory source of epidermal IL-10 protein. J Immunol 1994; 153:5256–5260.
Piskin G, Tursen U, Sylva-Steenland R, Bos J, Teunissen M. Clinical improvement in chronic plaque-type psoriasis lesions after narrow-band UVB therapy is accompanied by a decrease in the expression of IFN-gamma inducers, IL-12, IL-18 and IL-23. Exp Dermatol 2004; 13:764–772.
Sigmundsdottir H, Johnson A, Gudjonsson JE, Valdimarsson H. Narrowband-UVB irradiation decreases the production of pro-inflammatory cytokines by stimulated T cells. Arch Dermatol Res 2005; 297:39–41.
Feldman SR, Krueger GG. Psoriasis assessment tools in clinical trials. Ann Rheum Dis 2005; 64:65–68.
Long JW, Tao J, Pi XM. Effect of narrow-band UVB phototherapy on soluble cell adhesion molecules in patients with psoriasis vulgaris. J Int Med Res 2010; 38:1507–1512.
Bonifati C, Trento E, Carducci M. Soluble E-selectin and soluble tumor necrosis factor receptor (60 kD) serum levels in patients with psoriasis. J Dermatol 1995; 190:128–131.
Sigmundsdottir H, Johnston A, Gudjonsson JE, Bjarnason B, Valdimarsson H. Methotrexate markedly reduces the expression of vascular E-selectin, cutaneous lymphocyte-associated antigen and the numbers of mononuclear leucocytes in psoriatic skin. Exp Dermatol 2004; 13:426–434.
Borskà L, Fiala Z, Krejsek J. Selected immunological changes in patients with Goeckerman’s therapy TNF-alpha, sE-selectin, sP-selectin, sICAM-1 and IL-8. Physiol Res 2006; 55:699–706.
Herman S, Zurgil N, Deutsch M. Low dose methotrexate induces apoptosis with reactive oxygen species involvement in T lymphocytic cell lines to a greater extent than in monocytic lines. Inflamm Res 2005; 54:273–353.
Yamasaki E, Soma Y, Kawa Y, Mizoguchi M. Methotrexate inhibits proliferation and regulation of the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by cultured human umbilical vein endothelial cells. Br J Dermatol 2003; 149:30–38.
Elango T, Dayalan H, Subramanian S, Gnanaraj P, Malligarjunan H.Serum interleukin-6 in response to methotrexate treatment in psoriatic patients. Clin Chim Acta 2012; 413:1652–1656.
[Figure 1], [Figure 2]