|Year : 2022 | Volume
| Issue : 5 | Page : 512-517
|Serum soluble intercellular adhesion molecule-1 (sICAM-1): A novel potential biomarker in severe acne vulgaris
Amany Ibrahim Mustafa1, Adel Ali Ebrahim1, Waleed Abdel Lateef Abel Halim2, Eman Fawzy3, Ahmed Fathy Abdou4
1 Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Benha University, Egypt
2 Department of Clinical and Chemical Pathology, Faculty of Medicine, Benha University, Egypt
3 Department of Laboratory Medicine, Mansoura Fever Hospital, Ministry of Health, Egypt
4 Department of Dermatology, Mansoura Dermatology and Leprosy Hospital, Mansoura, Ministry of Health, Egypt
|Date of Web Publication||29-Dec-2022|
Amany Ibrahim Mustafa
Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Benha University - 13511
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Acne vulgaris (AV) is a chronic inflammatory disorder. Intercellular adhesion molecule-1 (ICAM-1) is a vital adhesion molecule mediating cellular adhesion during the inflammatory process. Aims and Objectives: To evaluate serum soluble intercellular adhesion molecule-1 (sICAM-1) level in AV patients as an attempt to elucidate its role in acne pathogenesis and to relate with studied clinical parameters. Materials and Methods: Serum sICAM-1 level was measured using ELISA technique in 60 patients and 60 controls. Results: Serum sICAM-1 level was significantly elevated in studied patients than controls (P < 0.001). Additionally, its level increased significantly with increased acne severity (P < 0.001) but not in patients with post acne scars (P > 0.05). Conclusion: Serum sICAM-1 could be a marker for acne etiopathogenesis. Furthermore, it might be considered as a predictor for disease severity.
Keywords: Acne vulgaris, inflammation, soluble intercellular adhesion molecule-1 (sICAM-1)
|How to cite this article:|
Mustafa AI, Ebrahim AA, Abel Halim WA, Fawzy E, Abdou AF. Serum soluble intercellular adhesion molecule-1 (sICAM-1): A novel potential biomarker in severe acne vulgaris. Indian J Dermatol 2022;67:512-7
|How to cite this URL:|
Mustafa AI, Ebrahim AA, Abel Halim WA, Fawzy E, Abdou AF. Serum soluble intercellular adhesion molecule-1 (sICAM-1): A novel potential biomarker in severe acne vulgaris. Indian J Dermatol [serial online] 2022 [cited 2023 Jan 31];67:512-7. Available from: https://www.e-ijd.org/text.asp?2022/67/5/512/366126
| Introduction|| |
Acne vulgaris (AV) is a widespread chronic disorder involving the pilosebaceous units. Its prevalence reaches up to 80% during adolescence. It can manifest as non-inflamed lesions and inflamed lesions or both. Several factors are implicated in AV pathogenesis, but inflammation is considered to be a primary factor. The process underlying the occurrence and continuity of the inflammatory response is not completely understood, but Cutibacterium acnes is a role player in these mechanisms., Inflammation precedes hyperkeratinization in early acne lesions.
Intercellular adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein in the immunoglobulin superfamily found at minimal amounts in a large array of cells and increases in response to various inflammation mediators. During inflammation, expressed ICAM-1 on the endothelial cells interacts with counter receptors on the surface of immune cells, enabling their trans-endothelial migration to the inflammatory sites.
High levels of soluble intercellular adhesion molecule-1 (sICAM-1) were detected in different inflammatory and immune-mediated diseases.,,,,, In spite of, the persistent inflammatory nature of AV, the role of sICAM-1 in this disease is not investigated. This work aims to assess serum sICAM-1 level in acne patients to elucidate its relationship with this common disease pathogenesis and its severity.
| Materials and Methods|| |
There were 120 people in this case–control research; 60 patients suffering from AV in addition to 60 apparently healthy control subjects. The purpose and nature of the study were described to all subjects, and informed consents form were taken from all participant as an agreement to be included in this research study. This study was conducted after local ethics committee approval and in agreement with Helsinki Declaration. Acne patients suffering from thyroid dysfunction, diabetes mellitus, hypertension, polycystic ovaries syndrome, chronic inflammatory or immune-mediated diseases, using treatment for acne 1 month before inclusion in the study, and pregnant or lactating females were all excluded from this work. Acne severity was assessed according to the Global Acne Grading System.
In plain test tubes, each subject's venous blood was collected in 5 ml under perfect aseptic conditions. Following coagulation, samples were centrifuged (at 1500 g for 15 min) and the separated serum was aliquoted and stored at –20°C for later assays of serum sICAM-1 level by using sICAM-1 ELISA Kit for research use (Cat#: E-EL-H2585, Elabscience Biotechnology Inc, USA).
Statistical analytic methods
SPSS version 25.0 was used to analyze the data. The significance of difference between the means of two investigated groups was determined using the Student's “t” test. The Mann–Whitney test (U test) was used to determine the significance of non-parametric variable differences between two groups. The Kruskal–Wallis test was used to determine the significance of differences in non-parametric variables between more than two groups. To investigate the relationship between two qualitative variables, the Chi-square test was performed. The strength of the link between two quantitative variables was determined using correlation analysis. The cutoff value for serum sICAM-1 level in illness prediction was determined using a receiver operating characteristic (ROC) curve. The risk factors for acne and acne scars were predicted using logistic and ordinal regression models. In this investigation, the significant level was set at a P value of 0.05.
| Results|| |
Baseline data of the study groups
Studied groups had matched age and sex. Among studied patients, 18 (30%) patients had mild, 26 (43.3%) patients had moderate, and 16 (26.7%) patients had severe acne lesions. Studied acne patients showed significantly higher serum sICAM-1 level compared to controls (P < 0.001; [Table 1]).
Serum sICAM-1 level showed an excellent Area under the ROC curve (AUC) (AUC = 0.988). At cutoff value of 277.8 ng/mL, sensitivity was 93.3%, specificity was 96.7%, Positive predictive value (PPV) was 96.6%, Negative predictive value (NPV) was 93.5%, and accuracy was 95% when ROC curve was conducted for diagnosis of AV [Figure 1].
Serum sICAM-1 level regarding studied clinical parameters
Significantly higher serum sICAM-1 level was detected in patients with severe AV than those with mild and moderate disease (P < 0.001). Otherwise, no significant relation was detected between serum sICAM-1 and other studied variables [Table 2] and [Table 3].
|Table 2: Relation between serum sICAM-1 level and studied parameters in AV patients group|
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|Table 3: Correlations between sICAM-1 level, patients' age, and disease duration|
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Prediction of AV susceptibility
Logistic regression analysis was conducted for prediction of AV development. Higher frequency of positive family history and higher serum sICAM-1 level were associated with the increased risk of AV susceptibility in univariable analysis. However, when significant confounders were analyzed jointly in multivariable analysis, only serum sICAM-1 level was suggested to be an independent risk predictor for AV development [Table 4].
Prediction of AV severity and post acne scars formation
Ordinal regression analysis was conducted for prediction of AV severity. Higher serum sICAM-1 was suggested to be an independent risk predictor for AV severity [Table 5]. But none of the studied factors was associated with post acne scars formation in studied AV patients when logistic regression analysis was conducted [Table 6].
|Table 6: Regression analysis for prediction of post acne scars formation|
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| Discussion|| |
Emerging data point that AV is an inflammatory disease, with multiple evidences indicating that the inflammatory response occurs during the entire stages of its development. The immunologic mechanisms beneath the onset and progression of inflammation in acne are not fully delineated. Acne lesions cause a shift in T helper type 1 (Th1) cells, and Th1-positive cells are more common in acne lesions than in normal skin. In terms of host responses to C. acnes in acne pathogenesis, bacteriological factors are more important than host immunological factors against C. acnes produced by peripheral blood mononuclear cells (PBMCs). Th17 cytokines, in addition to Th1 cytokines, play a role in acne development. C. acnes is a strong Th17 and Th1 inducer, and IL-17 is expressed in large numbers in acne lesions. Acne inflammation is mediated by IL-1 and TNF-α. As a result, controlling these cytokines could be a viable approach to treating acne.
Macrophages, CD3(+) cells, and CD4(+) cells are seen, as well as vascular adhesion molecules, E-selectin, and integrin activation. Inflammatory mediators implicated in acne as prospective targets are now part of our updated understanding of acne pathophysiology. Release of ICAM-1 controls cellular adhesion and circulating sICAM-1 level may be related to the variability in cell adhesion molecules expression and cell adhesion, hallmark of inflammation.
Elevated serum level of sICAM-1 reflects different pathologic conditions inflammatory in nature, such as Behcet's disease, systemic lupus erythematosus, rheumatoid arthritis, bullous pemphigoid, chronic urticarial, cutaneous vasculitis, and psoriasis.
In this study, serum sICAM-1 level was significantly higher in AV patients compared with control subjects. Additionally, when ROC curve of serum sICAM-1 level was conducted for diagnosis of AV, at a cutoff value of 277.8 ng/ml, sensitivity was 93.3%, specificity was 96.7%, PPV was 96.6%, NPV was 93.5%, and accuracy was 95%.
Different inflammatory cytokines are significantly increased in acne-involved skin when compared to the normal adjacent skin because of C. acnes colonization and through Toll-like receptors (TLRs) activation., Qin et al. provided an evidence on C. acnes contribution to the inflammation process in AV through activating NLRP3 inflammasome in antigen-presenting cells and eventually enhanced IL-1β production. It was found that the release of proinflammatory cytokine IL-1β induces sICAM-1 expression, through the p38 MAPK signalling pathway. Such mechanisms lead to inflammatory response and tissue damage in acne patients and increased severity of acne lesions.
Current findings revealed that serum sICAM-1 level increased significantly with increased disease severity and this could be related to the more prominent proinflammatory response. Also, ordinal regression analysis was conducted for prediction of AV severity. Higher serum sICAM-1 level was suggested to be an independent risk predictor for AV severity. Such finding is in accordance with other previous results reporting that ICAM-1 is constitutively expressed on the surface of endothelial cells and expression level increased as a result of tissue damage, inflammation, cellular stresses, virus infection, and environmental factors.,, Therefore, the more severe inflammation is, the higher expression of sICAM-1 will be. Otherwise, no significant associations were found regarding sICAM-1 level according to studied clinical data in the patients' group.
The association between sICAM-1 and fibrosis liability has been investigated in previous studies. High serum sICAM-1 levels had been reported in patients with idiopathic pulmonary fibrosis. Also, it was suggested that endothelial ICAM-1 is implicated in bleomycin-induced lung injury subsequent fibrosis. In addition, ICAM-1 signalling was reported to induce renal fibrosis. However, this study results did not find any relation between this biomarker levels and the liability for acne scars formation, possibly because of the modest sample included in this study and this needs future investigational work up.
The limitations of this study were the fairly small sample included in this work and it might be necessary to conduct future wide-ranging studies. Additionally, enrolled patients were included before or after treatment; therefore, future research measuring sICAM-1 levels prior to and after therapy would be more useful in evaluating the relation between its serum levels variation and therapeutic effectiveness. Finally, this work did not assess sICAM-1-producing cells, and so additional research is needed.
| Conclusions|| |
From the results of this work, it was concluded that serum sICAM-1 level was suggested to be an independent predictor of acne susceptibility and severity, but not post acne scars formation. Because acne is a problem in adolescence, the early assessment of this biomarker level may aid in management of this common disorder. A new knowledge of acne pathogenesis could help guide future treatment options.
We are grateful to all of the volunteers who participated in this study as well as the research team that gathered the data.
Compliance with Ethics Guidelines
The study was approved by the Local Ethics Committee on research involving human subjects in the Faculty of Medicine; Benha University in agreement with the Declaration of Helsinki. An informed consent was obtained from each subject prior to participation.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Knusten-Larson S, Dawson AL, Dunnick CA, Dellavalle RP. Acne vulgaris: Pathogenesis, treatment and needs assessment. DermatolClin 2012;30:99-106.
Ayer J, Burrows N. Acne: More than skin deep. Postgrad Med J 2006;82:500-6.
Bhate K, Williams HC.Epidemiology of acne vulgaris. Br J Dermatol 2013;168:474-85.
Zouboulis C, Eady A, Philpott M, Goldsmith LA, Orfanos C, Cunliffe WC, et al
. What is the pathogenesis of acne.ExpDermatol2005;14:143-52.
Simonart T.Immunotherapy for acne vulgaris: Current status and future directions.Am J ClinDermatol 2013;14:429-35.
Jeremy AH, Holland DB, Roberts SG, Thomson KF, Cunliffe WJ. Inflammatory events are involved in acne lesion initiation. J Invest Dermatol 2003;121:20-27.
Roebuck KA, Finnegan A. Regulation of intercellular adhesion molecule-1 (CD54) gene expression. J LeukocBiol 1999;66:876-88.
Orr IB, Martin de Carpi J, Dias JA, Levine A, Nuti F, Lionetti P, et al
. Evaluation of serum ICAM-1 and VCAM-1 as biomarkers for disease progression in Crohn's disease. JCrohn's Colitis 2017;11:208-20.
Przepiera-Będzak H, Fischer K, Brzosko M. Serum interleukin-18, fetuin-A, soluble intercellular adhesion molecule-1, and endothelin-1 in ankylosing spondylitis, psoriatic arthritis, and SAPHO syndrome.Int J MolSci 2016;17:1255.
Liu R-NG, Cheng Q-Y, Zhou H-Y, Li B-Z, Ye D-Q. Elevated blood and urinary ICAM-1 is a biomarker for systemic lupus erythematosus: Asystematic review and meta-analysis. Immunol Invest 2020;49:15-31.
Thakkar V, Patterson KA, Stevens W, Wilson M, Roddy J, Sahhar J, et al
. Increased serum levels of adhesion molecules ICAM-1 and VCAM-1 in systemic sclerosis are not specific for pulmonary manifestations. ClinRheumatol 2018;37:1563-71.
Wu BN, Wu J, Hao DL, Mao LL, Zhang LJ, Huang TT.High serum sICAM-1 is correlated with cerebral microbleeds and hemorrhagic transformation in ischemic stroke patients.Br JNeurosurg2018;32:631-6.
Wang Q, Xu Y, Qi C, Liu A, Zhao Y.Association study of serum soluble TREM2 with vascular dementia in Chinese Han population. Int J Neurosci 2020;130:708-12.
Ramli R, Malik AS, Hani AF, Jamil A. Acne analysis, grading and computational assessment methods: An overview. Skin Res Technol 2012;18:1-14.
Tanghetti EA. The role of inflammation in the pathology of acne. J ClinAesthetDermatol 2013;6:27-35.
Mouser PE, Baker BS, Seaton ED, Chu AC.Propionibacterium acnes-reactive T helper-1 cells in the skin of patients with acne vulgaris.J Invest Dermatol 2003;121:1226-8.
Sugisaki H, Yamanaka K, Kakeda M, Kitagawa H, Tanaka K, Watanabe K, et al
.Increased interferon-gamma, interleukin-12p40 and IL-8 production in Propionibacterium acnes-treated peripheral blood mononuclear cells from patient with acne vulgaris: Host response but not bacterial species is the determinant factor of the disease. J DermatolSci 2009;55:47-52.
Kim J. Review of the innate immune response in acne vulgaris: Activation of Toll-like receptor 2 in acne triggers inflammatory cytokine responses.Dermatology2005;211:193-8.
Kurokawa I, LaytonAM, Ogawa R. Updated treatment for acne: Targeted therapy based on pathogenesis. DermatolTher (Heidelb) 2021;11:1129-39.
Habas K, Shang L. Alterations in intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in human endothelial cells. Tissue Cell 2018;54:139-43.
Verity DH, Wallace GR, Seed PT, Kanawati CA, Ayesh I, Holland-Gladwish J, et al
. Soluble adhesion molecules in Behçet's disease. OculImmunolInflamm 1998;6:81-92.
Sabry A, Sheashaa H, El-Husseini A, El-Dahshan K, Abdel-Rahim M, Elbasyouni SR. Intercellular adhesion molecules in systemic lupus erythematosus patients with lupus nephritis. ClinRheumatol 2007;26:1819-23.
Macchioni P, Boiardi L, Casali B, Nicoli D, Farnetti E, Salvarani C. Intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms in Italian patients with rheumatoid arthritis. ClinExpRheumatol 2000;18:553-8.
Karashima T, Hachisuka H, Okubo K, Sasai Y. Epidermal keratinocytes of bullous pemphigoid express intercellular adhesion molecule-1 (ICAM-1). J Dermatol 1992;19:82-6.
Caproni M, Giomi B, Volpi W, Melani L, Schincaglia E, Macchia D, et al
. Chronic idiopathic urticaria: Infiltrating cells and related cytokines in autologous serum-induced wheals. ClinImmunol 2005;114:284-92.
Hayashi T, Hasegawa K, Ichinohe N. ICAM-1 expression on endothelium and systemic cytokine production in cutaneous neutrophilicleukocytoclasticvasculitis in NZBxNZWF1 mice. HistolHistopathol 2005;20:45-52.
Elias AN, Goodman MM, RohanMK.Serum ICAM-1 concentrations in patients with psoriasis treated with antithyroidthioureylenes. ClinExpDermatol 1993;18:526-29.
Demina O, Kartelishev A, Karpova E, Danischuk O.Role of cytokines in the pathogenesis of acne. Inter J Bio Med2017;7:37-40.
Qin M, Pirouz A, Kim MH, Krutzik SR, Garbán HJ, Kim J.Propioni-bacteriumacnesinducesIL-1betasecretionviatheNLRP3inflammasomeinhuman monocytes.J Invest Dermatol. 2014;134:381-8.
Guo J, Zhang H, Xia J, Hou J, Wang Y, Yang T, et al
.Interleukin-1β induces intercellular adhesion molecule-1 expression, thus enhancing the adhesion between mesenchymal stem cells and endothelial progenitor cells via the p38 MAPK signaling pathway. Int J Mol Med. 2018;41:1976-82.
Springer TA. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol 1995;57:827-72.
Monagas M, Khan N, Andres-Lacueva C, Casas R, Urpí-Sardà M, Llorach R, et al
.Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease. Am J ClinNutr 2009;90:1144-50.
Tsoutsou PG, Gourgoulianis KI, Petinaki E, Mpaka M, Efremidou S, Maniatis A, et al
.ICAM-1, ICAM-2 and ICAM-3 in the sera of patients with idiopathic pulmonary fibrosis. Inflammation 2004;28:359-64.
Chow FY, Nikolic-Paterson DJ, Ozols E, Atkins RC, Tesch GH.Intercellular adhesion molecule-1 deficiency is protective against nephropathy in type 2 diabetic db/db mice.J Am SocNephrol 2005;16:1711-22.
Sato N, Suzuki Y, Nishio K, Suzuki K, Naoki K, Takeshita K, et al
. Roles of ICAM-1 for abnormal leukocyte recruitment in the microcirculation of bleomycin-induced fibrotic lung injury. Am J RespirCrit Care Med2000;161:1681-8.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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