Soluble E-selectin serum leve/s in atopic dermatitis an.d psoriasis Comparison qf soluble E-selectin serum leve/s in two chronic i,iflammato,y skin diseases: atopic dermatitis and psoriasis J. C. Szepietowski, A. Blizanowska, A. Wasik and A. Noworolska ABSTRACT Background: Atopic dermatitis and psoriasis are common chronic cutaneous diseases of different pathogenetic aspects. Atopic dermatitis is considered as Th-2 and psoriasis as Th-1 type dermatosis, and this difference may lead to different expression of adhesion molecules. Objectives: This study was undertaken to evaluate soluble E-selectin serum levels in atopic dermatitis and psoriasis and to correlate its expression with the disease's severity. Material and methods: 16 patients suffering from atopic dermatitis, 20 psoriatic patients and 20 healthy individuals (control group) were included into the study. Soluble E-selectin serum levels were measured by ELISA using commercially available kits (R&D Systems). Severity of atopic dermatitis was assessed according to SCORAD and of psoriasis by PASI score. Results: The average serum level of soluble E-selectin in atopic dermatitis patients was 76.6±41.7 ng/ ml and did not significantly differ from that in psoriatic patients - 60.9±33.2 ng/ml. Soluble E-selectin serum levels both in atopic dermatitis and psoriasis were significantly increased (p<0.0002 and p<0.0005, respectively) compared to the control group, 28.7±9.5 ng/ml. Significant correlations (p<0.02) were found between soluble E-selectin serum levels and severity of atopic dermatitis and psoriasis. Conclusion: The enhanced endothelial activity (similar degree of activation) is a characteristic phe- nomenon for atopic dermatitis and psoriasis. The serum expression of soluble E-selectin could ·be used as a marker of disease's activity. Introduction Atopic dermatitis is a chronic inflammato1y skin clis- ease characterized by the infiltration in the dermis, which mainly consists ofT cells , monocytes and macrophages (1). Psoriasis is also a chronic inflammat.01y dermatosis markecl by hyperproliferation of epiclermis ancl mono- nuclear infiltrate in both dermis and epidermis (2,3) . Although both these cutaneous diseases are of chronic inflammatory type, their pathogenesis shows many dif- Clin.i c al study .14 --------------- ---- - - ----- - ---- - Acta Dermatoven APA Vol 11, 2002, No 1 Clinical study 80 70 60 50 40 30 20 10 O+-----------,-------~------< atopic dermatitis psoriasis controls Figure 1 . Soluble E-selectin serum levels in atopic dermatitis, psoriasis and control group. ferences. Atopic dermatitis is regarded asa Th2- or Th0- type disease (4,5) , whereas psoriasis is considered to be a Thl-type dermatosis (6). These variations result in production of different cytokines, which in turn could lead to different expressions of adhesion molecules on microvascular endothelium. E-selectin is a single chain glycoprotein adhesion molecule of molecular mass 115 kDa (7). It represents a recently described family of adhesion molecules: LEC- CAM (lectin, EGF, complement-related celi adhesion molecules) (8). E-selectin is crucially involved in the adherence between microvascular endothelium and monocytes, neutrophils, eosinophils and finally memory T cells (9,10). A soluble form of E-selectin (sE-selectin) has been identified and this form is nowadays regarded as a marker of endothelial cell activation (11). The aim of the present study was to evaluate and compare sE-selectin serum levels in two chronic inflam- matory diseases of different pathogenetic aspects to see if there was any difference in endothelial cell acti- vation between atopic dermatitis and psoriasis. More- 90 80 50 40 40 60 BO 100 sE-selectin 120 140 160 180 Figure 2. Correlation of sE-selectin serum levels and clinical activity of atopic dermatitis (SCORAD). Soluble E-selectin serum leve/s in atopic dermatitis and psoriasis o ver, we studied the possibility of using sE-selectin as a marker of the disease activity. Material and Method Patients Sixteen patients with typical atopic dermatitis and twenty patients suffering from psoriasis vulgaris were included in the study. The diagnosis of atopic dermati- tis was based on the criteria described by Rajka and Hanifin (12). The severity of atopic dermatitis was as- sessed according to SCORAD system (13) and of pso- riasis with psoriasis area and severity index (PASI) (14,15). The demographic details of the study groups are given in table 1. All these patients had not been treated with any systemic or topical drugs for at least 1 month before the beginning of the study. Twenty sex- and age-matched healthy individuals with no personal and family history of atopy and psoriasis served as con- trols. Measurement oj sE-selectin andlgE serum levels Eight milliliters of peripheral blood were collected from all individuals during the exacerbation of the dis- ease. After 60 min at room temperature the blood was centrifugated for 10 min, the serum was aspirated and frozen at -75°C until use. Soluble E-selectin was mea- sured by ELISA using a commercially available kit from R&D Systems (Abingdom, UK) (sensitivity <0.1 ng/ ml, sample volume 100 µl). The assays were performed strictly according to the manufacturer's instructions. Extinction was measured at 450 nm using an automatic analyzer (Stat Fax 2100, Awareness technology Inc., Palm City, FL, USA). Results were calculated from the standard curve of lyophilized recombinant human 55 45 35 25 15 20 40 60 sE-selectin BO 100 120 140 Figure 3. Correlation of sE-selectin serum levels and clinical activity of psoriasis (PASI). Acta Dermatoven APA Vol 11, 2002, No 1 - ----------------- 15 Soluble E-selectin serum leve/s in atopic dermatitis and psoriasis Table 1 . Demographic data of studied patients Number Gender (females/males) Age[ years] mean range Severity [ points] mean SCORAD range Duration of the disease [ years] mean range Duration of the last outbreak mean [ v\ttks] range soluble E-selectin and were expressed as ng/ml. More- over, in all atopic dermatitis patients' sera total IgE was measurecl by nephelometric method using commer- cially available reagents - N Latex IgE (Dade Behring Marburg GmbH, Marburg, Germany). Statistical analysis Mann-Whitney U.test and Spearman rang correla- tion were used to test statistical significance. P values less than 0.05 were considered significant. Results The average serum leve! of sE-selectin in atopic dermatitis patients was 76.6±41.7 ng/ml (range: 40-160 ng/ml) and was only slightly (not sign ificantly) higher that in psoriatic patients, 60.9±33.2 ng/ml (range: 22- 176 ng/ml). Soluble E-selectin serum levels both in pa- tients suffering from atopic dermatitis and psoriasis were significantly increased (p<0.0002 and p<0.0005, respec- tively) compared to healthy individuals, 28.7±9.5 ng/ ml (range: 16-48 ng/ml). Figure l. Moreover, a significant positive correlation (r=37, p<0.05) was demonstrated between sE-selectin serum levels and severity of atopic dermatitis assessed by SCORAD. Figure 2. Similarly, sE-selectin significantly correlated (r=42, p<0.02) with clinical intensity of pso- riasis (PASI). Figure 3. No relationships were observed between serum levels of sE-selectin and dura ti on of the cliseases, as well as cluration of the last exacerbations of atopic dermatitis and psoriasis . In atopic dermatitis pa- tients sE-selectin serum levels showed no association with serum IgE levels (clata not shown). Discussion E-selectin is involved in the recruitment of leuko- cytes to the site of inflammation, and is believed to play 16 20 5/11 9/11 44. 2±15.2 25.0±14.0 9-52 19-65 50.2±13.7 PASI 23.7±10.6 34-77.5 9.9-50.2 22.4±15.1 12.2±12.8 3-40 0.5-38 4.3±2.5 11.5±10.6 1-8 2-40 an important role in cletermining the intensity of an in- flammatory infiltrate (16, 17). Soluble form ofE-selectin was shown to be increased in a variety of inflammato1y and autoimmune diseases, inclucling arthritis (18), giant cell arteritis, scleroderma, systemic lupus e1ythemato- sus, polyartl1eritis nodosa (19) and seborrheic dermati- tis (20). Moreover, recently severa! researches found elevated serum leve! of sE-selectin in atopic dermatitis (17,20-27) and psoriasis (10,24,27-31), which is in agree- ment with our present observations. To the best of our knowledge there are only two reports directly compar- ing sE-selectin serum levels in these two common chronic inflammatory dermatoses, namely atopic der- matitis and psoriasis (24,27). Groves et al. (27) studied erythrodermic manifestations of both dermatoses and founc\ no significant clifference in serum expression of E-selectin. The present study, as the one by Czech et al. (24), demonstratec\ no markecl variations between se- ru m levels of sE-selectin in patients suffering from wide clinical spectra of atopic dermatitis and psoriasis; sig- nificant increase of this aclhesion molecule was how- ever, found in both clermatoses compared to the con- trol group. Atopic dermatitis and psoriasis differ in some pathological mechanisms Cl-6), the above mentioned findings suggest that in boili dermatoses the enclothe- lial celi activation is similarly enhanced. Kagi et al (32) however, postulated, that atopic dermatitis is a hetero- geneous disease w ith so-called extrinsic (allergic) ancl intrinsic (non-allergic) types. In their study two of thi-ee atopic dermatitis patients with normal sE-selectin lev- els were of intrinsic type (17) . These observations re- quire further studies . It is worth remembering that the ligancl for E-selectin is a cutaneous lymphocyte-associ- ated antigen (CIA), which is regardecl asa slzin-homing receptorand plays a crucial role in severa! dermatologi- cal conditions (26,33,34). Nowadays severa! immunological parameters are used as inarkers of diseases activity (10,35-37). Our study, showing significant positive correlation between sE-selectin values and SCORAD, confirms observations Clinical study 16 - ------- --- - - - --- - --- ---- ----------Acta Dermatoven APA Vol 11, 2002, No 1 Clinical study Soluble E-selectin serum leve/s in atopic dermatitis and psoriasis by others (20-27), that sE-selectin is a good marker of the clinical intensity of atopic dermatitis . Kagi et al (17) found significant correlation between changes in sE- selectin levels and the changes in scores for the sever- ity and extent of atopic dermatitis. They were unable to demonstrate significant relationship between sE- selectin values and both itch and sleep disturbance scores. This is in contrast to the data provided by Furue et al (26) who clearly showed association between sE- selectin levels and intensity of itch. Literature data on relationship between sE-selectin and IgE serum levels are limited and conflicting. We, as Morita et al. (23), found no association between two above mentionecl parameters, however, in another paper sE-selectin lev- els significantly correlated with total IgE levels (26). Increasecl IgE levels are frequently observed in atopic dermatitis patients, but this increase is not obligatory (17). Therefore , the differences in the evaluation of correlation between sE-selectin and IgE rnight be clue to different populations of patients. The opinions about possible use of sE-selectin in the evaluation of psoriasis severity are also controversial (10 ,24) . Recent studies (10,30,31), as the present one, suggest significant rela- tionship between sE-selectin sernm levels and extent of psoriatic lesions. Moreover, in our previous paper, we dernonstrated rnarked decrease of sE-selectin se- rum levels after effective treatment of psoriasis (10), ancl this may additionally argue for the usefulness of sE- selectin measurement as marker of disease intensity. Conclusion In conclusion, endothelial celi activation, as shown by sE-selectin serum levels, was enhanced in atopic dermatitis and psoriasis. The clegree of this increase is similar in both dermatoses. Moreover, serum levels of sE-selectin are believed to be aclequate markers of clis- ease activity in both atopic dermatitis and psoriasis. Acknowledgements This study was supported by grants No. 710 and 711 proviclecl by Wroclaw University of Medicine. lYJ,?J7'E, R ,:;, l'