Detection of serum and tissue levels of interleukin 39 in psoriasis: a case control study Mohammed Hassan 1 , Talal A. Abd El-Raheem 1 , Olfat G. Shaker 2 , Hagar Ali Kamal 1 , Sara M. Yaseen 1 ✉ , Amira E. Soliman 3 1 Department of Dermatology, Faculty of Medicine, Fayoum University, Fayoum, Egypt. 2 Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Fayoum, Egypt. 3 Department of Dermatology, Faculty of Medicine, Menoufia University, Shebein Elkom, Egypt. 45 2025;34:45-49 doi: 10.15570/actaapa.2025.13 Introduction Psoriasis is a chronic inflammatory skin disease characterized by the presence of scaly, well-demarcated papules and plaques that can appear anywhere on the body (1). Although topical treat- ments may suffice for mild or localized forms of psoriasis, sys- temic or biological therapies are often required for more severe or widespread cases. Over the past 2 decades, significant advances in understanding the immune-mediated pathophysiology of pso- riasis have led to the development of targeted biological agents for systemic treatment (2). Although the disease’s complex pathogenesis is not yet fully understood, recent studies have highlighted the critical role of the interleukin (IL)-23/17 axis, resulting in the emergence of therapies specifically designed to inhibit this pathway (3). Individuals with psoriasis are also known to have a higher risk of major adverse cardiovascular events, a connection that has been recognized for some time (4). Like other chronic inflammatory disorders such as atherosclerosis, psoriasis is thought to be driven by systemic in- flammatory mechanisms shared between the two conditions (5, 6). IL-39 is a heterodimeric cytokine composed of the IL-23p19 and Epstein–Barr virus–induced gene 3 (EBI3) subunits, and it has been implicated in modulating immune responses, particularly through its effects on neutrophil activation and pro-inflammatory signaling (7, 8). However, its specific role in the pathogenesis of psoriasis remains unclear. Assessing both tissue and serum IL-39 levels in patients with psoriasis may offer insights into its poten- tial contribution to disease mechanisms and its possible value as a biomarker for disease severity or therapeutic response (9). In addition, elevated serum IL-39 levels have been associated with left ventricular systolic dysfunction in individuals with ST-seg- ment elevation myocardial infarction, suggesting a broader role in systemic inflammation (10). To assess IL-39 expression, several detection methods can be utilized, including enzyme-linked immunosorbent assay (ELISA) for measuring serum levels, and immunohistochemistry (IHC), quantitative PCR (qPCR), and Western blotting for tissue analy- sis (11, 12). Detecting changes in IL-39 levels may provide new insights into the inflammatory mechanisms underlying psoria- sis and potentially reveal novel therapeutic targets (13, 14). This study investigates IL-39 variations in both blood and tissue sam- ples from individuals with psoriasis and evaluates its association with disease severity. Methods A prospective case-control study that included a total of 45 sub- jects classified into two cohorts: patients with psoriasis (n = 25) and a healthy control group (n = 20) was conducted at the outpa- tient clinic of the Dermatology Department, Faculty of Medicine, Fayoum University, Fayoum, Egypt. Ethical approval was grant- ed by the Ethics Committee of the Faculty of Medicine, Fayoum University (approval number M-399) on April 14th, 2019. Written informed consent was obtained from each participant prior to en- rollment. The study was carried out over a 6-month period, from May 2019 to October 2019. The study included patients of both sexes, between 20 and 70 years old, all diagnosed with plaque-type psoriasis. Individuals with erythrodermic, pustular, or palmoplantar forms of psoriasis, Abstract Introduction: Psoriasis is a chronic immune-mediated disorder with a genetic component that primarily affects the skin and has potential systemic involvement. Advances in understanding the interaction between the innate and adaptive immune systems have facilitated improved disease management. Methods: This study included 25 patients with psoriasis and 20 healthy controls of both sexes. All participants underwent detailed medical history-taking and dermatological examination, including assessment of the body surface area and the Psoriasis Area and Severity Index (PASI). Blood samples (3 ml) were collected from all subjects, and 4 mm lesional skin punch biopsies were obtained from psoriatic patients and healthy controls. Results: Serum and tissue levels of interleukin 39 (IL-39) were significantly elevated in psoriatic patients compared to healthy in- dividuals. Patients with a positive family history of psoriasis showed higher serum IL-39 levels than those without such a history. In addition, psoriatic individuals with diabetes mellitus or hypertension had higher serum IL-39 levels than those without these comorbidities. A statistically significant correlation was found between disease severity and serum IL-39 concentration. Conclusions: Elevated serum and tissue IL-39 levels in psoriatic patients suggest a potential role for IL-39 in the pathogenesis of psoriasis, highlighting its possible utility as a biomarker or therapeutic target. Keywords: psoriasis, cytokines, autoimmune disease, IL-39, ELISA Acta Dermatovenerologica Alpina, Pannonica et Adriatica Acta Dermatovenerol APA Received: 5 February 2025 | Returned for modification: 9 April 2025 | Accepted: 22 May 2025 ✉ Corresponding author: drsaramagdy1990@gmail.com 46 Acta Dermatovenerol APA | 2025;34:45-49 M. Hassan et al. nail psoriasis, or psoriatic arthritis were excluded. In addition, patients that had received systemic treatment for psoriasis within the previous 4 weeks were also excluded. The control cohort consisted of healthy volunteers of both sexes, with no personal or family history of psoriasis, and who were neither diabetic nor hypertensive. Each participant underwent a series of evaluations. This began with detailed history taking, including the onset, course, and duration of the disease, as well as past, family, and general medical history. A thorough dermatological examination was then conducted, during which the distribution of lesions and severity were assessed using the body surface area method (15), and psoriasis severity was quantified using the Psoriasis Area and Severity Index (PASI) score (16). For specimen collection, 3 ml of venous blood was drawn from each participant. In addition, a 4 mm lesional skin punch biopsy was obtained from psoriatic patients and matched sites in the controls. Quantitation of human IL-39 IL-39 levels were measured using an ELISA kit (Bioassay Technol- ogy Laboratory, Shanghai, China; cat. no. E7444Hu). The assay is based on a sandwich ELISA principle, in which human IL-39 in the sample binds to antibodies pre-coated on the plate. A bi- otinylated detection antibody specific to IL-39 is then added, fol- lowed by the binding of streptavidin- horseradish peroxidase. Af- ter washing to remove unbound components, a substrate solution is added, inducing a color change proportional to the amount of IL-39 present. The reaction is halted with an acidic stop solution, and absorbance is measured at 450 nm. Statistical analysis Data were analyzed using SPSS version 17.0 (IBM, New York, USA). Descriptive statistics for qualitative data were expressed as numbers and percentages. For quantitative parametric data, re- sults were expressed as means and standard deviations. To compare two independent groups with parametric data, an independent Student’s t-test was used. When comparing more than two independent groups, a one-way ANOVA was performed, fol- lowed by Bonferroni post-hoc analysis for significance at p < 0.05. For non-parametric quantitative data, comparisons among more than two groups were made using the Kruskal–Wallis test, and the Mann–Whitney U test was applied for pairwise comparisons. To assess relationships between variables in qualitative data, the two-tailed bivariate Pearson correlation test was used. Diagnos- tic accuracy was evaluated using the receiver operating character- istic (ROC) curve, including sensitivity and specificity assessments. A p-value of less than 0.05 was considered statistically significant. Results Demographic data and sex distribution Table 1 summarizes the demographic characteristics. There was no statistically significant difference in age between patients and controls. The mean age was 40.80 ± 12.03 years in the control group and 38.55 ± 11.25 years in the psoriasis group (p = 0.525). Patient ages ranged from 21 to 66 years, and control participant ages ranged from 22 to 56 years. Psoriasis severity, assessed using the PASI score, ranged from 5.60 to 56.80 with a mean of 20.42 ± 11.53. Disease duration had a median of 96 months (range: 8 to 360 months). Based on sever- ity, 18 patients (72%) were classified as moderate, four (16%) as severe, and three (12%) as mild. Relation between IL-39 levels in serum and tissue between the cohorts The IL-39 concentration levels were evaluated in both tissue and se- rum for patients with psoriasis and compared to healthy controls. The IL-39 level in serum was high in the patient cohort compared to the healthy control, with medians of 461.36 ng/l and 148.62 ng/l, respectively. The IL-39 level in tissue also tended to be elevated in the patient cohort compared to the controls, with a median of 353.46 ng/mg versus 176.61 ng/mg. There was a significant differ- ence between both cohorts regarding IL-39 levels in tissue and se- rum, with p-values of 0.001 and 0.0001, respectively (Table 2). Relation between IL-39 concentration level in serum and various characteristics in the psoriasis cohort The IL-39 concentration level in serum was evaluated among pa- tients with psoriasis and compared accordingly with the descrip- tive and clinical data of the patients. The results revealed that there was a significant difference between IL-39 and sex, whereby female patients had higher IL-39 levels than males, with a median of 611.32 ng/l and 187.05 ng/l, respectively, with a p-value of 0.05. There was also a significant difference between IL-39 and fam- ily history, at p = 0.05. The IL-39 level in serum was elevated in patients with a positive family history of psoriasis in comparison to patients with a negative family history, with medians of 611.34 ng/l and 187.04 ng/l, respectively. No significance was found for other parameters, including hy- pertension, diabetes mellitus, and the extent of the disease, at p > 0.05 (Table 3). Relation between IL-39 concentration level in patients’ serum and disease severity After evaluating the IL-39 concentration level in serum in relation to disease severity based on the PASI score, the results showed that patients classified as mild had a median IL-39 concentration Table 1 | Demographic data of patients. a One-way ANOVA, b chi-squared test, *significant at p < 0.05. SD = standard deviation. Parameters Psoriasis (n = 25) Control (n = 20) p-value Age (years), mean ± SD 40.80 ± 12.03 38.55 ± 11.25 0.525 a Sex, n (%) Female 10 (40) 6 (30) 0.497 b Male 15 (60) 14 (70) Family history, n (%) 6 (24) 0 (0) 0.009* Hypertension, n (%) 5 (20) 0 (0) 0.003* Diabetes mellitus, n (%) 4 (16) 0 (0) 0.001* Table 2 | Interleukin-39 concentration levels in serum and tissue between pa- tient and healthy control cohort. Data are shown as median (range). A chi-squared test was used, and the Mann– Whitney U test for significance. *Significant at p < 0.05. IL = interleukin. Biomarkers Psoriasis Control p-value IL-39 serum (pg/ml) 461.36 (56.64–2000.00) 148.62 (63.02–206.70) 0.0001* IL-39 tissue (pg/mg) 353.46 (191.41–741.62) 176.61 (122.45–232.54) 0.001* 47 Acta Dermatovenerol APA | 2025;34:45-49 Detection of interleukin 39 in psoriasis level of 719.36 ng/l. In contrast, in moderate and severe patients the median IL-39 level tended to be lower, at 438.00 ng/l and 154.90 ng/l, respectively. There was a remarkable difference be- tween the mild patients and moderate patients with regard to the IL-39 level, with a p-value of 0.020, as well as between severe and mild patients, with a p-value of 0.04. Relation between IL-39 concentration level in tissue and various characteristics in the psoriasis cohort The IL-39 concentration level was assessed, and the results showed that there was no significant relation between IL-39 level and other parameters, including sex, family history, hyper- tension, diabetes mellitus, or even the extent of the disease, at p > 0.05. Relation between IL-39 concentration level in patients’ tissue and disease severity Based on the PASI score, the results showed that the IL-39 level tended to decrease with the severity of psoriasis. Patients diag- nosed with mild psoriasis had an IL-39 concentration level of 379.43 ng/mg as the median. For patients with moderate and severe psoriasis, the median IL-39 levels were 366.66 ng/mg and 260.94 ng/mg, respectively. There was no significant variation between patient cohorts regarding the IL-39 level in tissue, at p > 0.05. Correlation between serum and tissue IL-39 concentration levels and descriptive/clinical data After assessing the bivariate correlation utilizing Pearson’s r be- tween the IL-39 serum biomarker and descriptive and clinical data among patients with psoriasis, the findings showed that there were no correlations between age (r = 0.065, p = 0.758), disease duration (r = −0.043, p = 0.837), extent of the disease (r = −0.223, p = 0.284), or PASI score (r = −0.241, p = 0.245) and the IL-39 con- centration level in serum. Regarding the IL-39 concentration level in tissue, the results showed that there was also no correlation between IL-39 and age (r = 0.262, p = 0.206), disease duration (r = −0.178, p = 0.395), ex- tent of the disease (r = −0.46, p = 0.29), or PASI score (r = −0.037, p = 0.862). Sensitivity and specificity of IL-39 biomarker in the patient cohort Based on the calculation of IL-39 levels in serum and tissue sam- ples from patients with psoriasis, the applied values of IL-39 were determined as indicators for psoriasis diagnosis. ROC curves were utilized for analysis. The results show that the area under the curve (AUC) and the cutoff value of IL-39 in serum were 0.84 and 403.94 pg/ml with specificity and sensitivity of 72% and 97.5%, re- spectively, at p < 0.0001. For the IL-39 level in tissue, AUC was 0.98 at the cutoff value of 294.43 pg/mg with sensitivity and specificity of 98.0% and 98.5%, respectively, at p < 0.0001. Relation between serum and tissue IL-39 concentration levels in psoriasis To measure the relationship between the IL-39 concentration level in both serum and tissue, a model was conducted for which IL-39 was the dependent variable. Based on linear regression analysis, the unstandardized coefficient was −0.423 with a standard error of 0.792. For the standardized coefficient, the beta value was −0.111, t-value = −0.535, and p-value = 0.036. Thus, IL-39 in serum is con- sidered a dependent variable for psoriasis with IL-39 in tissue in the diagnosis of the disease. Discussion Psoriasis is characterized by an overactive immune system and uncontrolled keratinocyte proliferation, both central features of its pathophysiology. Immune dysregulation plays a key role in disease development. For moderate to severe cases, biologi- cal therapies targeting cytokines such as tumor necrosis factor (TNF)-α, IL-12/IL-23, IL-17, and IL-23/IL-39 have been approved. The cytokine-driven molecular mechanisms underlying psoriasis are closely linked to its clinical manifestations (17). In this study, IL-39 concentration levels were assessed in both serum and tissue samples of psoriatic patients. The results showed significant elevation of IL-39 levels in both compared to healthy controls. Although age and sex distributions did not show statistically significant differences between the groups, the major- ity of patients were male. IL-39 shares structural and functional features with other members of the IL-12 cytokine family, including IL-12, IL-23, IL-27, and IL-35. These cytokines commonly influence T-cell differentia- tion and immune cell activation. For example, IL-23 supports the differentiation and maintenance of Th17 cells, which are pivotal in autoimmune inflammation. Although IL-39’s exact mechanism of action remains unclear, it may exert complementary or antagonis- tic effects within this cytokine network (18). Some research suggests that IL-39 can induce proinflammatory cytokines such as IL-6 and IL-8, indicating potential interplay with inflammatory signaling pathways. However, one study evaluating IL-39’s effect on human neutrophils reported that exposure to IL-39 did not significantly alter mRNA expression levels of IL-6 or IL-8. This finding suggests that IL-39 may not directly induce these cy- tokines in neutrophils, at least under the conditions studied (11). Conversely, in murine models, IL-39 has been implicated in Table 3 | Interleukin-39 concentration level in serum by patient cohort param- eters. Parameters IL-39 (pg/ml) in serum Psoriasis patients (n = 25) p-value Sex Female (n = 10) 611.32 (56.64–1528.50) 0.05* Male (n = 15) 187.05 (105.09–2,000.00) Family history Negative (n = 19) 187.04 (56.64–2,000.00) 0.05* Positive (n = 6) 611.34 (403.94–719.36) Hypertension Negative (n = 20) 286.10 (56.64–2,000.00) 0.080 Positive (n = 5) 611.34 (403.94–719.36) Diabetes mellitus Negative (n = 21) 385.17 (56.64–2,000.00) 0.114 Positive (n = 4) 665.35 (611.32–719.36) Extent < 20% (n = 8) 611.34 (56.64–1,528.50) 0.722 > 20% (n = 17) 403.94 (129.44–2,000.00) Data are shown as median (range). A chi-squared test was used, and the Mann– Whitney U test for significance. *Significant at p < 0.05. IL = interleukin. 48 Acta Dermatovenerol APA | 2025;34:45-49 M. Hassan et al. promoting inflammatory responses. Research has shown that IL- 39 can induce the differentiation and expansion of neutrophils, which are key players in inflammation. These neutrophils, in turn, can secrete various proinflammatory mediators, potentially including IL-6 and IL-8, although direct measurements of these cytokines in response to IL-39 were not reported in the study (19). To the best of our knowledge, the IL-39 concentration level was not previously measured in psoriasis. However, IL-12, which shares structural and functional similarities with IL-39, was re- ported to be higher in the lesions of psoriatic patients than non- lesional control skin, showing a significant difference between lesions of psoriatic patients and healthy controls (20). A study of thirty patients and ten healthy controls concluded that IL-12 may play a vital role in the development of active psoriatic lesions (20). Another study that examined the levels of IL-17A, IL-10, IL-23A, IL-17RA, and IL-23R expressions in the skin of sixty psoriatic pa- tients showed that the levels of interleukins tended to be higher in lesions of psoriatic patients when compared to healthy controls, with a significant difference between both cohorts (21). Mouse models with psoriasis generally showed that cytokines (IL-23 and IL-12) that were released from inflammatory myeloid dendritic cells activate IL-17–producing T cells, Th1 cells, and Th22 cells, and it was concluded that these cytokines mediate impacts on ke- ratinocytes to increase psoriatic inflammation (22). The IL-12 family is important in the development and mainte- nance of autoimmune responses, and so IL-39 could be implicated in other skin autoimmune diseases, such as psoriasis. The pro- inflammatory effects of IL-39 have been previously identified, in which macrophages, dendritic cells, and B cells are the produc- ing cells, and neutrophils are the immune cells responding. It is linked to systemic lupus erythematosus in lupus-prone mice (23). Currently, no specific IL-39 inhibitors are approved for clinical use, and research on therapeutic targeting of IL-39 remains in the preclinical stage. However, the inhibition of IL-39, either directly or indirectly, could be a potential therapeutic strategy in inflam- matory diseases, particularly if further studies confirm its role in promoting proinflammatory cytokines and neutrophil activation. Experimental models suggest that blocking IL-39 signaling could potentially reduce inflammatory responses, making it a promising candidate for future drug development (24, 25). To date, there are limited specific data on the relationship be- tween IL-39 and nail or joint involvement in psoriatic disease. Most studies have focused on cutaneous manifestations or sys- temic inflammatory responses. However, given that IL-39 may con- tribute to the recruitment and activation of neutrophils and other immune cells implicated in psoriatic arthritis and nail psoriasis, it is plausible that IL-39 also plays a role in these disease domains. Future studies focusing on IL-39 levels in patients with psoriatic nail disease or psoriatic arthritis are needed to clarify this poten- tial association. Including assessments of IL-39 in these subtypes could expand the understanding of its broader relevance in the psoriatic disease spectrum (26, 27). There is currently a lack of direct evidence on how methotrex- ate or narrowband ultraviolet B (NB-UVB) phototherapy specifi- cally influence IL-39 levels. However, both treatments are known to downregulate systemic inflammation and reduce the expres- sion of various proinflammatory cytokines such as IL-6, IL-17, and TNF-α. Given IL-39’s presumed role in amplifying inflammation via neutrophilic activation and cytokine induction, it is plausible that effective anti-inflammatory therapies such as methotrexate and NB-UVB may also reduce IL-39 levels (28). Contradicting our findings, the IL-39 level was measured in au- toimmune thyroid disease in serum, and the results revealed that the IL-39 concentration level tended to be lower in patients than in healthy controls. Among patients with Hashimoto’s thyroiditis and Graves’ disease, the IL-39 level was slightly lower than in the control cohort, with a statistically significant difference between cohorts (29). In this study, the PASI score was calculated for all patients, and the majority of the patient cohort was diagnosed as moderately psoriatic. There was a high statistically significant difference be- tween disease severity in the serum IL-39 concentration level. In agreement with our findings, several studies have demon- strated that serum IL-39 levels tend to rise with increasing severity of various inflammatory and autoimmune conditions, including neuromyelitis optica spectrum disorder (30), hepatitis / liver in- jury (31), type 2 diabetes mellitus (8), rheumatoid arthritis (32), and lupus (24). IL-39 shares the p19 subunit with IL-23. In a study investigat- ing IL-23A- and/or EBI3-containing cytokines in psoriatic patients, the authors observed that IL-23 was significantly upregulated in psoriatic skin lesions. They concluded that therapies targeting the IL-23Ap19 subunit, such as anti-IL-23Ap19 antibodies, are highly effective in managing psoriasis (33). Another study involving 39 psoriatic patients and 30 healthy controls found that elevated lev- els of IL-23, along with TNF-α, interferon (IFN)-γ, IL-6, IL-1β, IL-18, and IL-17A, were associated with higher PASI scores (29). This study found no significant differences in the IL-39 level in the tissue of psoriatic patients regarding disease severity. Howev- er, the IL-39 level tended to increase as the disease severity wors- ened. No statistically significant correlations were detected be- tween serum or tissue IL-39 and PASI score, nor between IL-39 and the extent of the lesion in psoriatic patients or the duration of the disease. Studies on IL-39 are limited, and more research is needed to determine its levels in tissues of various skin conditions. The small sample size of the participants and their heterogene- ity regarding the severity of the disease are the major limitations of this study. Conclusions The detection of serum and tissue IL-39 levels in psoriasis pro- vides valuable insights into its potential role in the disease’s pathogenesis. 49 Acta Dermatovenerol APA | 2025;34:45-49 Detection of interleukin 39 in psoriasis References 1. Gisondi P, Fostini AC, Fossà I, Girolomoni G, Targher G. Psoriasis and the meta- bolic syndrome. Clin Dermatol. 2018;36:21–8. 2. Raharja A, Mahil SK, Barker JN. Psoriasis: a brief overview. Clin Med (Lond). 2021;21:170–3. 3. Puri P, Nandar S, Kathuria S, Ramesh V. Effects of air pollution on the skin: a review. Indian J Dermatol Venereol Leprol. 2017;83:415–23. 4. Ormaza Vera A, Yap A, Perkins-Holtsclaw KJ, Van Voorhees AS, Enos CW. Major adverse cardiovascular events are more frequent in psoriasis patients compared to controls, despite statin therapy: an observational retrospective cohort study. J Am Acad Dermatol. 2024;91:1254–6. 5. Garshick MS, Ward NL, Krueger JG, Berger JS. Cardiovascular risk in patients with psoriasis. J Am Coll Cardiol. 2021;77:1670–80. 6. Rendon A, Schäkel K. Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019 23;20:1475. 7. Lu Z, Xu K, Wang X, Li Y, Li M. Interleukin 39: a new member of interleukin 12 family. Cent Eur J Immunol. 2020;45:214–7. 8. Nussrat SW, Ad’hiah AH. Interleukin-39 is a novel cytokine associated with type 2 diabetes mellitus and positively correlated with body mass index. Endocrinol Diabetes Metab. 2023;6:e409. 9. Turchin I, Bourcier M. The role of interleukins in the pathogenesis of dermato- logical immune-mediated diseases. Adv Ther. 2022;39:4474–508. 10. Luo Y, Liu F, Liu H, Chen H, Cheng W, Dong S, et al. Elevated serum IL-39 in pa- tients with ST-segment elevation myocardial infarction was related with left ven- tricular systolic dysfunction. Biomark Med. 2017;11:419–26. 11. Ecoeur F, Weiss J, Schleeger S, Guntermann C. Lack of evidence for expression and function of IL-39 in human immune cells. PLoS One. 2020;15:e0242329. 12. Sari A, Dogan S, Nibali L, Koseoglu S. Evaluation of IL-23p19/Ebi3 (IL-39) gin - gival crevicular fluid levels in periodontal health, gingivitis, and periodontitis. Clin Oral Investig. 2022;26:7209–18. 13. Guo J, Zhang H, Lin W, Lu L, Su J, Chen X. Signaling pathways and targeted thera- pies for psoriasis. Signal Transduct Target Ther. 2023;8:437. 14. Campanati A, Marani A, Martina E, Diotallevi F, Radi G, Offidani A. Psoriasis as an immune-mediated and inflammatory systemic disease: from pathophysiol- ogy to novel therapeutic approaches. Biomedicines. 2021;9:1511. 15. Thom D. Appraising current methods for preclinical calculation of burn size—a pre-hospital perspective. Burns. 2017;43:127–36. 16. Mattei PL, Corey KC, Kimball AB. Psoriasis Area Severity Index (PASI) and the Dermatology Life Quality Index (DLQI): the correlation between disease sever- ity and psychological burden in patients treated with biological therapies. J Eur Acad Dermatology Venereol. 2014;28:333–7. 17. Singh R, Koppu S, Perche PO, Feldman SR. The cytokine mediated molecular pathophysiology of psoriasis and its clinical implications. Int J Mol Sci. 2021;22: 12793. 18. Ellergezen PH, Kizmaz MA, Simsek A, Demir N, Cagan E, Bal SH, et al. Investi- gation of IL-35 and IL-39, new members of the IL-12 family, in different clinical presentations of brucellosis. Immunol Invest. 2023;52:286–97. 19. Bridgewood C, Alase A, Watad A, Wittmann M, Cuthbert R, McGonagle D. The IL- 23p19/EBI3 heterodimeric cytokine termed IL-39 remains a theoretical cytokine in man. Inflamm Res. 2019;68:423–6. 20. Shaker OG, Moustafa W, Essmat S, Abdel-Halim M, El-Komy M. The role of inter- leukin-12 in the pathogenesis of psoriasis. Clin Biochem. 2006;39:119–25. 21. Kutwin M, Migdalska-Sęk M, Brzeziańska-Lasota E, Zelga P, Woźniacka A. An analysis of IL-10, IL-17A, IL-17RA, IL-23A and IL-23R expression and their correla - tion with clinical course in patients with psoriasis. J Clin Med. 2021;10:5834. 22. Lowes MA, Suárez-Fariñas M, Krueger JG. Immunology of psoriasis. Annu Rev Immunol. 2014;32:227–55. 23. Catalan-Dibene J, McIntyre LL, Zlotnik A. Interleukin 30 to interleukin 40. J Interf Cytokine Res. 2018;38:423–39. 24. Wang X, Wei Y, Xiao H, Liu X, Zhang Y, Han G, et al. A novel IL-23p19/Ebi3 (IL- 39) cytokine mediates inflammation in lupus-like mice. Eur J Immunol. 2016;46: 1343–50. 25. Lv K, Hu B, Xu M, Wan L, Jin Z, Xu M, et al. IL-39 promotes chronic graft-versus- host disease by increasing T and B cell pathogenicity. Exp Hematol Oncol. 2022; 11:34. 26. Sobolewski P, Walecka I, Dopytalska K. Nail involvement in psoriatic arthritis. Reumatologia. 2017;55:131–5. 27. Zhou XY, Zhang JA, Chen K. Nail psoriasis: treatment options and management strategies in special patient populations. Int J Dermatology Venereol. 2022;5: 32–9. 28. Elghandour TM, Youssef SES, Aly DG, Abd Elhameed MS, Abdel Moneim MM. Effect of narrow band ultraviolet B therapy versus methotrexate on serum levels of interleukin-17 and interleukin-23 in Egyptian patients with severe psoriasis. Dermatol Res Pract. 2013;2013:1–6. 29. Weng L, Huang G, Gong L, Xu J, Mao Y, Li Y, et al. Low levels of serum IL-39 are associated with autoimmune thyroid disease. J Clin Lab Anal. 2022;36. 30. Yang MG, Tian S, Zhang Q, Han J, Liu C, Zhou Y, et al. Elevated serum interleu- kin-39 levels in patients with neuromyelitis optica spectrum disorders corre- lated with disease severity. Mult Scler Relat Disord. 2020;46:102430. 31. Li Y, Gong L, Weng L, Pan X, Liu C, Li M. Interleukin-39 exacerbates concanavalin A-induced liver injury. Immunopharmacol Immunotoxicol. 2021;43:94–9. 32. Ying L, Gong L, Meng S, Wu X, Li M, Li Y . Circulating interleukin-39 as a potential biomarker for rheumatoid arthritis diagnosis. Clin Biochem. 2023;119:110616. 33. Tachibana K, Tang N, Urakami H, Kajita A, Kobashi M, Nomura H, et al. Multifac- eted analysis of IL-23A- and/or EBI3-including cytokines produced by psoriatic keratinocytes. Int J Mol Sci. 2021;22:12659.