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Volume 17, Issue 2 (2025)
Iran J War Public Health 2025, 17(2): 183-189 |
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Ethics code: 33 in 23/10/2024
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Received: 2025/05/6 | Accepted: 2025/06/26 | Published: 2025/07/4
Received: 2025/05/6 | Accepted: 2025/06/26 | Published: 2025/07/4
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Abbas E, Rasheed S, Naser L, Hassan E, Bader R. CCL20 Serum Levels as a Biomarker for Psoriasis Severity and Disease-Related Comorbidities. Iran J War Public Health 2025; 17 (2) :183-189
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1- Department of Pathology and Forensic Medicine, Faculty of Medicine, University of Kufa, Najaf, Iraq
2- Department of Medical Microbiology, Faculty of Medicine, University of Kufa, Najaf, Iraq
3- Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Kufa, Najaf, Iraq
2- Department of Medical Microbiology, Faculty of Medicine, University of Kufa, Najaf, Iraq
3- Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Kufa, Najaf, Iraq
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Introduction
Psoriasis is a chronic, persistent, immune-mediated inflammatory skin disease affecting approximately 2-3% of the global population [1]. It typically presents as well-defined, red plaques covered with silvery-white scales, most frequently affecting the elbows, knees, scalp, and lower back. The pathogenesis of psoriasis is multifactorial and involves a dynamic interplay between genetic predisposition, environmental triggers, and immune system dysregulation [2, 3].
The immunopathogenesis of psoriasis involves a complex network of cellular and molecular interactions. Central to this process is the dysregulation of adaptive immune responses, particularly the activation of specific T cell subsets. At the core of this immune dysregulation is the aberrant activation of T lymphocytes, especially the Th1, Th17, and Th22 subsets, which secrete pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-17 (IL-17), and interleukin-23 (IL-23). These cytokines create a self-sustaining inflammatory loop that promotes keratinocyte hyperproliferation, epidermal thickening, and the recruitment of additional immune cells, culminating in the formation of psoriatic plaques.
Dendritic cells play a pivotal role in initiating the inflammatory cascade by producing cytokines such as IL-23 and TNF-α, which drive the differentiation and maintenance of Th17 cells. These Th17 cells, in turn, release IL-17A, IL-17F, and IL-22, which act directly on keratinocytes to enhance their proliferation and trigger the production of antimicrobial peptides and additional inflammatory mediators. Keratinocytes are not merely passive targets; they actively contribute to the inflammatory milieu by releasing cytokines such as IL-1β, IL-6, and chemokines like CCL20. These molecules amplify the immune response by recruiting additional immune cells, especially CCR6-expressing Th17 cells, into the dermis and epidermis [4, 5].
Chemokines represent a class of small signaling proteins that are critical mediators of leukocyte movement and tissue-specific immune responses [6-8]. In psoriasis, several chemokines and their receptors are upregulated in lesional skin, promoting and driving the infiltration of Th17 cells, neutrophils, and monocytes. Key examples include the CCL20-CCR6 axis, as well as CXCL1, CXCL8, CXCL9, CXCL10, and CXCL11, all of which work in concert with pro-inflammatory cytokines such as IL-17, IL-23, IFN-γ, and TNF-α to amplify local inflammation and tissue damage [9-11]. Additionally, certain chemokines like CXCL12 and its receptor CXCR4 contribute to angiogenesis and vascular inflammation, further supporting their role in disease progression [12, 13].
Among these, chemokine (C-C motif) ligand 20 (CCL20), also known as macrophage inflammatory protein-3 alpha (MIP-3α), plays a pivotal role in the development and progression of psoriasis by recruiting CCR6-expressing immune cells, particularly Th17 cells, regulatory T cells (Tregs), and dendritic cells (DCs), into psoriatic lesions [14]. Elevated CCL20 expression has been observed in lesional skin and appears to contribute to both local and systemic immune activation. The CCL20-CCR6 axis is now recognized as a major component of the psoriatic inflammatory cascade [15].
Recent research suggests that serum levels of CCL20 may reflect disease activity and systemic immune involvement in psoriasis. Elevated circulating levels of CCL20 have been associated not only with skin inflammation but also with psoriatic comorbidities, including psoriatic arthritis, metabolic syndrome, and cardiovascular disease [16-18]. This highlights the potential of CCL20 as a biomarker for disease severity and for stratifying the risk of systemic complications.
Therefore, the present study aimed to assess serum CCL20 levels in patients with psoriasis and to evaluate their association with disease severity and the presence of comorbid conditions.
Instrument and Methods
This cross-sectional study was conducted at Merjan Teaching Hospital in Hilla City, Babylon Province, during the period from October 2024 to January 2025. It comprised 68 patients with psoriasis (24 females and 44 males), with ages ranging from 18 to 65 years.
Informed consent was obtained from each participant after a clear description of the study’s purpose, and demographic and clinical data of the patients were collected (duration of disease, family history, weight, treatment of psoriasis, disease comorbidities, aggravating factors, and complications). All patients were evaluated for obesity using body mass index (BMI) according to the WHO classification [19].
Patients were clinically diagnosed by a dermatologist. Disease severity was evaluated using the Psoriasis Area and Severity Index (PASI) and categorized into mild, moderate, and severe psoriasis groups [20]. The study excluded subjects who were pregnant, those with diseases other than psoriasis, such as other skin and inflammatory diseases, and patients who had not received biologic therapy in the last three months.
Blood sample collection
Five milliliters of venous blood were collected from patients with psoriasis. Blood samples were allowed to clot, and then serum was separated using centrifugation and stored at -24°C until used. Serum levels of CCL20 were measured using an enzyme-linked immunosorbent assay (ELISA) kit (BT. LAB, China; Cat. No. E6513Hu), following the manufacturer’s instructions.
Statistical analysis
For statistical analysis, SPSS software (version 26) was used. Descriptive statistics were employed to summarize the information, calculating averages and standard deviations (or standard errors) for continuous data and reporting counts and percentages for categorical data. To compare two separate groups, independent samples t-tests were utilized. For comparisons of three or more groups, a one-way ANOVA test was performed. Pearson’s correlation coefficient was used to examine the relationships between numerical measurements. Statistical significance was determined if the p-value was less than or equal to 0.001 or less than or equal to 0.05. values are expressed as mean±standard error of the mean.
Findings
A total of 68 patients with psoriasis, including 24 (35.3%) females and 44 (64.7%) males, participated in the study. The mean age was 38.15±14.40 years, with a minimum age of 18 years and a maximum age of 65 years. The mean duration of the disease was 38.15±14.40 years. Obese patients constituted 38.2% of the study population, compared to 61.8% of non-obese patients, with a mean BMI of approximately 30kg/m2 for all study participants (mean BMI value was 29.47±6.20kg/m2). Half of the patients suffered from severe disease, and 61.8% of them experienced disease complications. Also, the PASI score was 29.37±6.20. Several complications were observed among patients, including metabolic syndrome (14 patients, 20.6%), ischemic heart disease (IHD; 28 patients, 41.2%), and psoriatic arthritis (12 patients, 17.6%; Table 1).
Table 1. Some demographic and clinical characteristics of psoriasis patients
The mean serum CCL20 levels in psoriasis patients were 112.14±8.72ng/L, with values ranging from 42.89 to 293.50ng/L. The mean CCL20 levels were higher in patients with mild disease (207.96±13.88) compared to those with moderate disease (132.68±15.76) and severe disease (78.31 ± 6.48) (p-value=0.0001). The difference observed in CCL20 levels was statistically significant across the severity groups. The results showed a negative and significant correlation between PASI (the index of severity) and CCL20 levels (Figure 1).
Figure 1. Correlation between Psoriasis Area and Severity Index (PASI) score and serum CCL20 levels (p=0.0001)
There was no significant difference in CCL20 levels between patients who were obese and those who were not, as well as between patients with and without ischemic heart disease (IHD) (p=0.24 and p=0.84, respectively). In contrast, patients with metabolic syndrome had significantly higher CCL20 levels (168.77±25.07) compared to those without (97.45±7.83) (p=0.001. Notably, patients with psoriatic arthritis had significantly lower CCL20 levels (57.63±8.05) compared to those without (123.82±9.80) (p=0.003; Table 2).
Table 2. Association between serum CCL20 levels and complications in psoriasis patients
Discussion
This study aimed to assess serum CCL20 levels in patients with psoriasis and to evaluate their association with disease severity and the presence of comorbid conditions. Psoriasis is a multifaceted, chronic immune-mediated disorder that primarily affects the skin and nails. However, growing research highlights its strong link to systemic inflammation, which extends beyond dermatological manifestations. Studies suggest that persistent inflammation in psoriasis patients contributes to the development of complications, including cardiovascular diseases and insulin resistance. This association underscores the need for a comprehensive approach to managing psoriasis, not only to control skin symptoms but also to mitigate the risk of serious systemic complications.
We presented a demographic and clinical profile of psoriasis patients, offering insights into potential factors associated with disease severity and complications. The patients were predominantly male, and the long disease duration reflects the chronic nature of psoriasis. A notable proportion of patients were smokers and/or obese. Both smoking and obesity are recognized aggravating factors for psoriasis, contributing to chronic systemic inflammation and potentially influencing disease severity. The mean BMI fell within the overweight to obese range, which supports the notion of metabolic involvement in the pathogenesis of psoriasis [21].
In terms of disease severity, a majority of patients had moderate and severe psoriasis based on the PASI score, suggesting that more than 90% of the study population had significant disease activity. This may reflect referral bias or a focus on moderate-to-severe cases in the study design. The presence of complications was common, with the most frequent comorbid conditions being ischemic heart disease, obesity, metabolic syndrome, and psoriatic arthritis. These findings are consistent with current literature, which emphasizes the systemic nature of psoriasis and its association with increased cardiovascular and metabolic risks [22, 23].
Chemokines, specifically CCL20, play an essential role in the development of psoriasis and participate in the progression of the disease by influencing disease severity and contributing to various complications. Our results revealed a statistically significant inverse relationship between psoriasis severity and serum CCL20 levels. Patients with mild psoriasis exhibited the highest mean CCL20 levels, which progressively declined in moderate and severe cases. According to Brunner et al., there is an elevation in the serum levels of this type of chemokine in psoriasis patients [24]. This trend contrasts with much of the existing literature, which typically reports positive correlations between CCL20 levels and disease severity, as the role of CCL20 chemokine in Th17 recruitment and chronic inflammation in psoriatic lesions has been well established [13, 14].
One possible explanation for this unexpected pattern could be related to the dynamic nature of the complex relationship between cytokine and chemokine expression throughout disease progression. In the early or moderate stages, CCL20 may serve as a primary driver of inflammation, particularly by attracting CCR6+ immune cells, especially Th17 cells, to the skin. However, in severe psoriasis, the inflammatory profile becomes more complex, potentially dominated by other mediators such as TNF-α, IL-17A, and IL-22. These mediators may become more dominant, potentially affecting CCL20 levels and altering the role of the CCL20 pathway in disease progression and expression or distribution. Therefore, CCL20 plays a significant role in recruiting inflammatory cells to psoriatic lesions at the beginning, exacerbating the inflammatory process [15].
Individual variability in immune response and comorbid conditions, such as obesity and smoking status, may also affect CCL20 expression. Given that these factors influence systemic inflammation, they could modulate chemokine profiles differently across patient subgroups.
Our study differs from the research by Harper et al., which indicates that Th17 cytokines, such as IL-17A and IL-22, significantly upregulate CCL20 expression in human keratinocytes. This upregulation facilitates the recruitment of CCR6+ Th17 cells into psoriatic lesions, contributing to the disease’s progression [18]. Additionally, Furue et al. showed that CCL20 is constitutively expressed in cultured keratinocytes [25].
These results may also be attributed to the body’s regulatory mechanisms in severe psoriasis, where negative feedback loops are likely activated to mitigate excessive inflammation, potentially leading to reduced systemic production or release of CCL20. Moreover, in advanced stages of the disease, a substantial portion of CCL20 may be sequestered within psoriatic skin lesions, resulting in lower measurable levels in the serum despite ongoing local inflammation [14].
Accordingly, it appears that CCL20 levels in the skin increase with the progression of psoriasis, which may differ from its serum levels due to the influence of multiple factors, most notably its abundant production by keratinocytes. This discrepancy might explain the findings in our study, where higher levels of CCL20 in the blood were linked to less severe psoriasis and vice versa.
The severity of psoriasis is influenced by a range of factors, including genetic predisposition, environmental triggers, and associated comorbidities. Variability in cytokine and chemokine profiles among individuals may impact study findings, as differences in patient composition across severity groups can contribute to variations in observed outcomes [26, 27].
This inverse correlation challenges some conventional assumptions and underscores the need for further research to explore the temporal and contextual roles of CCL20 in psoriasis progression. Longitudinal studies and stratification based on treatment status may help clarify these findings.
In addition to its role in cutaneous inflammation, CCL20 is implicated in the development of systemic comorbidities in psoriasis patients, such as psoriatic arthritis, metabolic dysfunction, and cardiovascular complications, through its involvement in chronic immune activation and Th17 cell recruitment [27].
We examined the association between serum CCL20 levels and several selected comorbid conditions in patients with psoriasis (obesity, metabolic syndrome, ischemic heart disease, and psoriatic arthritis) and found a strong association and significant findings regarding the serum levels of CCL20 in relation to metabolic syndrome and psoriatic arthritis. While the mean chemokine levels were numerically higher in the obese group than in the non-obese group, the difference was not statistically significant. Several factors may explain this finding, such as the relatively small sample size, which could limit statistical power and make it difficult to detect moderate associations. Additionally, chemokine expression may be more pronounced locally in adipose tissue rather than in systemic circulation. Furthermore, inconsistent chemokine levels across individuals may also result from variability in assay methods and differences in regulatory pathways, such as NF-κB [28, 29]. These considerations suggest that while chemokines play a role in inflammation, their relationship with obesity is complex and may not be adequately captured in small or unstratified cohorts.
IHD showed no significant association with chemokines. This outcome could be attributed to the fact that chemokine levels in circulation might vary depending on whether the individual is experiencing acute coronary syndrome or stable chronic IHD. Since the study likely included patients with stable disease, this condition often shows less systemic chemokine elevation [30].
Regarding the relationship with metabolic syndrome, this result aligns with current evidence from Rocha & Libby, Bellinato et al., and Zhang & Wu [13, 31, 32]. One study suggested that metabolic deregulation enhances systemic inflammation and chemokine expression. These studies indicate that adipose tissue dysfunction in metabolic syndrome increases the release of pro-inflammatory cytokines, such as IL-6 and TNF-α, which may stimulate an increased production of the chemokine CCL20 in keratinocytes and immune system cells [33].
There was a relationship between serum CCL20 levels and psoriatic arthritis, showing significantly lower levels in patients with psoriatic arthritis compared to those without joint involvement. Although CCL20 is a key chemokine in Th17 cell trafficking and synovial inflammation, this inverse association may reflect local tissue sequestration of CCL20 in joint compartments or immune exhaustion/adaptation in chronic disease. Additionally, many psoriatic arthritis patients may be undergoing systemic immunosuppressive therapy, which could potentially lower serum CCL20 levels [34, 35]. These observations highlight the need for further investigation into the site-specific expression of CCL20 and its regulatory mechanisms in the pathophysiology of psoriatic arthritis.
A limitation of the study is that it is a snapshot observational study, which could not establish a clear timeline or prove cause and effect between CCL20 levels, psoriasis severity, and comorbidities.
We recommend further research to explore the temporal and contextual roles of CCL20 in psoriasis progression by conducting longitudinal studies with continuous measurement and follow-up.
Conclusion
There is an inverse relationship between serum CCL20 levels and the severity of psoriasis, and serum CCL20 levels are significantly associated with metabolic syndrome among psoriatic patients.
Acknowledgments: The researchers would like to extend their thanks to all the workers in the Department of Medical Microbiology, Faculty of Medicine, University of Kufa, for their valuable support in completing the research requirements.
Ethical Permissions: The study was authorized by the Bioethics Committee in the Faculty of Medicine, University of Kufa (ethical approval No. 33 on 23/10/2024).
Conflicts of Interests: All authors declared no conflicts of interests.
Authors' Contribution: Abbas EC (First Author), Introduction Writer/Methodologist/Main Researcher (30%); Rasheed SM (Second Author), Assistant Researcher/Discussion Writer (30%); Naser LH (Third Author), Assistant Researcher/Discussion Writer (20%); Hassan ES (Fourth Author), Assistant Researcher/Methodologist/Statistical Analyst (10%); Bader RM (Fifth Author), Introduction Writer/Assistant Researcher (10%)
Funding/Support: This is a self-funded study, with all authors participating in the costs.
Psoriasis is a chronic, persistent, immune-mediated inflammatory skin disease affecting approximately 2-3% of the global population [1]. It typically presents as well-defined, red plaques covered with silvery-white scales, most frequently affecting the elbows, knees, scalp, and lower back. The pathogenesis of psoriasis is multifactorial and involves a dynamic interplay between genetic predisposition, environmental triggers, and immune system dysregulation [2, 3].
The immunopathogenesis of psoriasis involves a complex network of cellular and molecular interactions. Central to this process is the dysregulation of adaptive immune responses, particularly the activation of specific T cell subsets. At the core of this immune dysregulation is the aberrant activation of T lymphocytes, especially the Th1, Th17, and Th22 subsets, which secrete pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-17 (IL-17), and interleukin-23 (IL-23). These cytokines create a self-sustaining inflammatory loop that promotes keratinocyte hyperproliferation, epidermal thickening, and the recruitment of additional immune cells, culminating in the formation of psoriatic plaques.
Dendritic cells play a pivotal role in initiating the inflammatory cascade by producing cytokines such as IL-23 and TNF-α, which drive the differentiation and maintenance of Th17 cells. These Th17 cells, in turn, release IL-17A, IL-17F, and IL-22, which act directly on keratinocytes to enhance their proliferation and trigger the production of antimicrobial peptides and additional inflammatory mediators. Keratinocytes are not merely passive targets; they actively contribute to the inflammatory milieu by releasing cytokines such as IL-1β, IL-6, and chemokines like CCL20. These molecules amplify the immune response by recruiting additional immune cells, especially CCR6-expressing Th17 cells, into the dermis and epidermis [4, 5].
Chemokines represent a class of small signaling proteins that are critical mediators of leukocyte movement and tissue-specific immune responses [6-8]. In psoriasis, several chemokines and their receptors are upregulated in lesional skin, promoting and driving the infiltration of Th17 cells, neutrophils, and monocytes. Key examples include the CCL20-CCR6 axis, as well as CXCL1, CXCL8, CXCL9, CXCL10, and CXCL11, all of which work in concert with pro-inflammatory cytokines such as IL-17, IL-23, IFN-γ, and TNF-α to amplify local inflammation and tissue damage [9-11]. Additionally, certain chemokines like CXCL12 and its receptor CXCR4 contribute to angiogenesis and vascular inflammation, further supporting their role in disease progression [12, 13].
Among these, chemokine (C-C motif) ligand 20 (CCL20), also known as macrophage inflammatory protein-3 alpha (MIP-3α), plays a pivotal role in the development and progression of psoriasis by recruiting CCR6-expressing immune cells, particularly Th17 cells, regulatory T cells (Tregs), and dendritic cells (DCs), into psoriatic lesions [14]. Elevated CCL20 expression has been observed in lesional skin and appears to contribute to both local and systemic immune activation. The CCL20-CCR6 axis is now recognized as a major component of the psoriatic inflammatory cascade [15].
Recent research suggests that serum levels of CCL20 may reflect disease activity and systemic immune involvement in psoriasis. Elevated circulating levels of CCL20 have been associated not only with skin inflammation but also with psoriatic comorbidities, including psoriatic arthritis, metabolic syndrome, and cardiovascular disease [16-18]. This highlights the potential of CCL20 as a biomarker for disease severity and for stratifying the risk of systemic complications.
Therefore, the present study aimed to assess serum CCL20 levels in patients with psoriasis and to evaluate their association with disease severity and the presence of comorbid conditions.
Instrument and Methods
This cross-sectional study was conducted at Merjan Teaching Hospital in Hilla City, Babylon Province, during the period from October 2024 to January 2025. It comprised 68 patients with psoriasis (24 females and 44 males), with ages ranging from 18 to 65 years.
Informed consent was obtained from each participant after a clear description of the study’s purpose, and demographic and clinical data of the patients were collected (duration of disease, family history, weight, treatment of psoriasis, disease comorbidities, aggravating factors, and complications). All patients were evaluated for obesity using body mass index (BMI) according to the WHO classification [19].
Patients were clinically diagnosed by a dermatologist. Disease severity was evaluated using the Psoriasis Area and Severity Index (PASI) and categorized into mild, moderate, and severe psoriasis groups [20]. The study excluded subjects who were pregnant, those with diseases other than psoriasis, such as other skin and inflammatory diseases, and patients who had not received biologic therapy in the last three months.
Blood sample collection
Five milliliters of venous blood were collected from patients with psoriasis. Blood samples were allowed to clot, and then serum was separated using centrifugation and stored at -24°C until used. Serum levels of CCL20 were measured using an enzyme-linked immunosorbent assay (ELISA) kit (BT. LAB, China; Cat. No. E6513Hu), following the manufacturer’s instructions.
Statistical analysis
For statistical analysis, SPSS software (version 26) was used. Descriptive statistics were employed to summarize the information, calculating averages and standard deviations (or standard errors) for continuous data and reporting counts and percentages for categorical data. To compare two separate groups, independent samples t-tests were utilized. For comparisons of three or more groups, a one-way ANOVA test was performed. Pearson’s correlation coefficient was used to examine the relationships between numerical measurements. Statistical significance was determined if the p-value was less than or equal to 0.001 or less than or equal to 0.05. values are expressed as mean±standard error of the mean.
Findings
A total of 68 patients with psoriasis, including 24 (35.3%) females and 44 (64.7%) males, participated in the study. The mean age was 38.15±14.40 years, with a minimum age of 18 years and a maximum age of 65 years. The mean duration of the disease was 38.15±14.40 years. Obese patients constituted 38.2% of the study population, compared to 61.8% of non-obese patients, with a mean BMI of approximately 30kg/m2 for all study participants (mean BMI value was 29.47±6.20kg/m2). Half of the patients suffered from severe disease, and 61.8% of them experienced disease complications. Also, the PASI score was 29.37±6.20. Several complications were observed among patients, including metabolic syndrome (14 patients, 20.6%), ischemic heart disease (IHD; 28 patients, 41.2%), and psoriatic arthritis (12 patients, 17.6%; Table 1).
Table 1. Some demographic and clinical characteristics of psoriasis patients
The mean serum CCL20 levels in psoriasis patients were 112.14±8.72ng/L, with values ranging from 42.89 to 293.50ng/L. The mean CCL20 levels were higher in patients with mild disease (207.96±13.88) compared to those with moderate disease (132.68±15.76) and severe disease (78.31 ± 6.48) (p-value=0.0001). The difference observed in CCL20 levels was statistically significant across the severity groups. The results showed a negative and significant correlation between PASI (the index of severity) and CCL20 levels (Figure 1).
Figure 1. Correlation between Psoriasis Area and Severity Index (PASI) score and serum CCL20 levels (p=0.0001)
There was no significant difference in CCL20 levels between patients who were obese and those who were not, as well as between patients with and without ischemic heart disease (IHD) (p=0.24 and p=0.84, respectively). In contrast, patients with metabolic syndrome had significantly higher CCL20 levels (168.77±25.07) compared to those without (97.45±7.83) (p=0.001. Notably, patients with psoriatic arthritis had significantly lower CCL20 levels (57.63±8.05) compared to those without (123.82±9.80) (p=0.003; Table 2).
Table 2. Association between serum CCL20 levels and complications in psoriasis patients
Discussion
This study aimed to assess serum CCL20 levels in patients with psoriasis and to evaluate their association with disease severity and the presence of comorbid conditions. Psoriasis is a multifaceted, chronic immune-mediated disorder that primarily affects the skin and nails. However, growing research highlights its strong link to systemic inflammation, which extends beyond dermatological manifestations. Studies suggest that persistent inflammation in psoriasis patients contributes to the development of complications, including cardiovascular diseases and insulin resistance. This association underscores the need for a comprehensive approach to managing psoriasis, not only to control skin symptoms but also to mitigate the risk of serious systemic complications.
We presented a demographic and clinical profile of psoriasis patients, offering insights into potential factors associated with disease severity and complications. The patients were predominantly male, and the long disease duration reflects the chronic nature of psoriasis. A notable proportion of patients were smokers and/or obese. Both smoking and obesity are recognized aggravating factors for psoriasis, contributing to chronic systemic inflammation and potentially influencing disease severity. The mean BMI fell within the overweight to obese range, which supports the notion of metabolic involvement in the pathogenesis of psoriasis [21].
In terms of disease severity, a majority of patients had moderate and severe psoriasis based on the PASI score, suggesting that more than 90% of the study population had significant disease activity. This may reflect referral bias or a focus on moderate-to-severe cases in the study design. The presence of complications was common, with the most frequent comorbid conditions being ischemic heart disease, obesity, metabolic syndrome, and psoriatic arthritis. These findings are consistent with current literature, which emphasizes the systemic nature of psoriasis and its association with increased cardiovascular and metabolic risks [22, 23].
Chemokines, specifically CCL20, play an essential role in the development of psoriasis and participate in the progression of the disease by influencing disease severity and contributing to various complications. Our results revealed a statistically significant inverse relationship between psoriasis severity and serum CCL20 levels. Patients with mild psoriasis exhibited the highest mean CCL20 levels, which progressively declined in moderate and severe cases. According to Brunner et al., there is an elevation in the serum levels of this type of chemokine in psoriasis patients [24]. This trend contrasts with much of the existing literature, which typically reports positive correlations between CCL20 levels and disease severity, as the role of CCL20 chemokine in Th17 recruitment and chronic inflammation in psoriatic lesions has been well established [13, 14].
One possible explanation for this unexpected pattern could be related to the dynamic nature of the complex relationship between cytokine and chemokine expression throughout disease progression. In the early or moderate stages, CCL20 may serve as a primary driver of inflammation, particularly by attracting CCR6+ immune cells, especially Th17 cells, to the skin. However, in severe psoriasis, the inflammatory profile becomes more complex, potentially dominated by other mediators such as TNF-α, IL-17A, and IL-22. These mediators may become more dominant, potentially affecting CCL20 levels and altering the role of the CCL20 pathway in disease progression and expression or distribution. Therefore, CCL20 plays a significant role in recruiting inflammatory cells to psoriatic lesions at the beginning, exacerbating the inflammatory process [15].
Individual variability in immune response and comorbid conditions, such as obesity and smoking status, may also affect CCL20 expression. Given that these factors influence systemic inflammation, they could modulate chemokine profiles differently across patient subgroups.
Our study differs from the research by Harper et al., which indicates that Th17 cytokines, such as IL-17A and IL-22, significantly upregulate CCL20 expression in human keratinocytes. This upregulation facilitates the recruitment of CCR6+ Th17 cells into psoriatic lesions, contributing to the disease’s progression [18]. Additionally, Furue et al. showed that CCL20 is constitutively expressed in cultured keratinocytes [25].
These results may also be attributed to the body’s regulatory mechanisms in severe psoriasis, where negative feedback loops are likely activated to mitigate excessive inflammation, potentially leading to reduced systemic production or release of CCL20. Moreover, in advanced stages of the disease, a substantial portion of CCL20 may be sequestered within psoriatic skin lesions, resulting in lower measurable levels in the serum despite ongoing local inflammation [14].
Accordingly, it appears that CCL20 levels in the skin increase with the progression of psoriasis, which may differ from its serum levels due to the influence of multiple factors, most notably its abundant production by keratinocytes. This discrepancy might explain the findings in our study, where higher levels of CCL20 in the blood were linked to less severe psoriasis and vice versa.
The severity of psoriasis is influenced by a range of factors, including genetic predisposition, environmental triggers, and associated comorbidities. Variability in cytokine and chemokine profiles among individuals may impact study findings, as differences in patient composition across severity groups can contribute to variations in observed outcomes [26, 27].
This inverse correlation challenges some conventional assumptions and underscores the need for further research to explore the temporal and contextual roles of CCL20 in psoriasis progression. Longitudinal studies and stratification based on treatment status may help clarify these findings.
In addition to its role in cutaneous inflammation, CCL20 is implicated in the development of systemic comorbidities in psoriasis patients, such as psoriatic arthritis, metabolic dysfunction, and cardiovascular complications, through its involvement in chronic immune activation and Th17 cell recruitment [27].
We examined the association between serum CCL20 levels and several selected comorbid conditions in patients with psoriasis (obesity, metabolic syndrome, ischemic heart disease, and psoriatic arthritis) and found a strong association and significant findings regarding the serum levels of CCL20 in relation to metabolic syndrome and psoriatic arthritis. While the mean chemokine levels were numerically higher in the obese group than in the non-obese group, the difference was not statistically significant. Several factors may explain this finding, such as the relatively small sample size, which could limit statistical power and make it difficult to detect moderate associations. Additionally, chemokine expression may be more pronounced locally in adipose tissue rather than in systemic circulation. Furthermore, inconsistent chemokine levels across individuals may also result from variability in assay methods and differences in regulatory pathways, such as NF-κB [28, 29]. These considerations suggest that while chemokines play a role in inflammation, their relationship with obesity is complex and may not be adequately captured in small or unstratified cohorts.
IHD showed no significant association with chemokines. This outcome could be attributed to the fact that chemokine levels in circulation might vary depending on whether the individual is experiencing acute coronary syndrome or stable chronic IHD. Since the study likely included patients with stable disease, this condition often shows less systemic chemokine elevation [30].
Regarding the relationship with metabolic syndrome, this result aligns with current evidence from Rocha & Libby, Bellinato et al., and Zhang & Wu [13, 31, 32]. One study suggested that metabolic deregulation enhances systemic inflammation and chemokine expression. These studies indicate that adipose tissue dysfunction in metabolic syndrome increases the release of pro-inflammatory cytokines, such as IL-6 and TNF-α, which may stimulate an increased production of the chemokine CCL20 in keratinocytes and immune system cells [33].
There was a relationship between serum CCL20 levels and psoriatic arthritis, showing significantly lower levels in patients with psoriatic arthritis compared to those without joint involvement. Although CCL20 is a key chemokine in Th17 cell trafficking and synovial inflammation, this inverse association may reflect local tissue sequestration of CCL20 in joint compartments or immune exhaustion/adaptation in chronic disease. Additionally, many psoriatic arthritis patients may be undergoing systemic immunosuppressive therapy, which could potentially lower serum CCL20 levels [34, 35]. These observations highlight the need for further investigation into the site-specific expression of CCL20 and its regulatory mechanisms in the pathophysiology of psoriatic arthritis.
A limitation of the study is that it is a snapshot observational study, which could not establish a clear timeline or prove cause and effect between CCL20 levels, psoriasis severity, and comorbidities.
We recommend further research to explore the temporal and contextual roles of CCL20 in psoriasis progression by conducting longitudinal studies with continuous measurement and follow-up.
Conclusion
There is an inverse relationship between serum CCL20 levels and the severity of psoriasis, and serum CCL20 levels are significantly associated with metabolic syndrome among psoriatic patients.
Acknowledgments: The researchers would like to extend their thanks to all the workers in the Department of Medical Microbiology, Faculty of Medicine, University of Kufa, for their valuable support in completing the research requirements.
Ethical Permissions: The study was authorized by the Bioethics Committee in the Faculty of Medicine, University of Kufa (ethical approval No. 33 on 23/10/2024).
Conflicts of Interests: All authors declared no conflicts of interests.
Authors' Contribution: Abbas EC (First Author), Introduction Writer/Methodologist/Main Researcher (30%); Rasheed SM (Second Author), Assistant Researcher/Discussion Writer (30%); Naser LH (Third Author), Assistant Researcher/Discussion Writer (20%); Hassan ES (Fourth Author), Assistant Researcher/Methodologist/Statistical Analyst (10%); Bader RM (Fifth Author), Introduction Writer/Assistant Researcher (10%)
Funding/Support: This is a self-funded study, with all authors participating in the costs.
Keywords:
References
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