Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2024;14(3):e2024177 1 Gasdermin A (GSDMA) Tissue Expression, Serum and Urinary Concentrations with Clinicopathologic Outcome in Psoriasis Julia Nowowiejska1, Anna Baran1, Anna Pryczynicz2, Justyna Magdalena Hermanowicz3, Beata Sieklucka3, Dariusz Pawlak3, Iwona Flisiak1 1 Department of Dermatology and Venereology, Medical University of Bialystok, Bialystok, Poland 2 Department of General Pathomorphology, Medical University of Bialystok, Bialystok, Poland 3 Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland Key words: gasdermin A, GSDMA, pyroptosis, psoriasis, hyperkeratosis Citation: Nowowiejska J, Baran A, Pryczynicz A, et al. Gasdermin A (GSDMA) Tissue Expression, Serum and Urinary Concentrations With Clinicopathologic Outcome in Psoriasis. Dermatol Pract Concept. 2024;14(3):e2024177. DOI: https://doi.org/10.5826/dpc.1403a177 Accepted: April 3, 2024; Published: July 2024 Copyright: ©2024 Nowowiejska et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: The part of the study involving the assessment of serum and urinary GSDMA was funded by the National Science Center, Poland, no NCN/1/MI/22/001/1149. The part of the study involving the assessment of tissue expression of GSDMA was funded by the Medical University of Bialystok, Poland, no B.SUB.23.358. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Julia Nowowiejska MD, PhD, Department of Dermatology and Venereology, Medical University of Bialystok, Bialystok, Poland. E-mail: julia.nowowiejska@umb.edu.pl Introduction: Psoriasis is a frequent and incurable skin disease that is an important issue in contem- porary dermatology, although its pathogenesis is still uncertain. Gasdermin A (GSDMA) is a member of the gasdermin protein family which are able to cause pore formation in cellular membranes leading to cell death called pyroptosis. Objective: Our aim was to investigate the role of GSDMA in psoriatic patients. Method: The study enrolled 60 patients with active plaque-type psoriasis and 30 sex- and age-matched volunteers without dermatoses. GSDMA concentration was assessed in serum and urine samples of all participants using ELISA. GSDMA tissue expression was assessed by immunohistochemistry. Results: GSDMA serum concentration was significantly higher in patients compared to controls, whereas urinary GSDMA/creatinine ratio was insignificantly lower. GSDMA tissue expression was more prominent in psoriatic plaque compared to non-lesional patients’ skin and healthy skin of sub- jects without dermatoses. There was a strong negative correlation between GSDMA serum concentra- tion and ALT activity. GSDMA did not correlate with PASI or psoriasis duration. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2024;14(3):e2024177 Introduction Psoriasis is a common chronic dermatosis that occurs with an average frequency of 2% worldwide [1]. Although this disease is a constant subject of scientists’ investigations, its pathogenesis is still not fully understood. It encompasses genetic predisposition and complex immunological distur- bances, additionally exacerbated by external stimuli [2,3]. The microscopic picture of psoriasis consists of the areas of acanthosis (epidermal hyperplasia) and parakeratosis in the stratum corneum with mounds of neutrophils (Munro’s microabscesses), inflammatory infiltrates in the dermis, and dilated vessels in dermal papillae [4]. Clinically, such ab- normalities translate into erythematous-scaly lesions called psoriatic plaques [4]. Due to the clinical appearance of the lesions and sometimes their significant exacerbation and un- favorable localization, psoriasis may impair the quality of patients’ lives and ability to work [5,6]. Nowadays, there is a wide range of antipsoriatic therapies, both topical and systemic agents, including biological agents, yet the disease is not permanently curable [7,8]. That makes it an important problem of contemporary dermatology. Gasdermins are a group of proteins that are made up of similar two-domain molecular structure, namely globular N- and C-terminal domains separated by a flexible linker region [9]. Their properties and functions are still being dis- covered, but available data point to their pleiotropic impact [10]. They have been associated with cell proliferation and differentiation. They are engaged in immune response, in- flammation, and tumorigenesis [11]. Most importantly, they play a role in cell death via different pathways. Their unique chemical structure allows them to be executors of pyroptosis – the inflammatory cell death type resulting in the formation of pores in cellular membranes and the release of inflamma- tory cytokines [12]. It has been shown that cells that express gasdermins are determined to die in order to become a part of the cornified layer of the skin or the hardened tube of the inner root sheath or to disintegrate and release lipid com- pounds [13]. The name of the whole group - ‘gasdermins’ - originates from gasdermins’ expression in the gastrointestinal tract and skin. This is exactly where the first member of this family is mainly observed – gasdermin A (GSDMA) [14]. Its en- coding gene is located on chromosome 17q21.1 [15], and it has the ability to participate not only in pyroptosis but also in apoptosis by activating caspase 3 and 7 or via trans- forming growth factor β (TGF-β) [12]. So far, GSDMA has been implicated in the pathogenesis of asthma, inflammatory bowel diseases, systemic sclerosis, streptococcal infections in humans, and alopecia in mice [16-20]. Surprisingly, it has been suggested that GSDMA is probably not essential for the maintenance of the skin barrier, but its role emerges when pathogens or other stimuli appear, and that is related to the further path of GSDMA activation [14]. Our interest in GSDMA originated from the reports that a mutation in GSDMA gene in mice causes hyperplasia of the epidermis, which is exactly what we see in psoriatic skin [4,20,21]. Therefore, it would be valuable to investigate the role of GSDMA in psoriasis. Objective Considering the role of GSDMA in cell proliferation and dif- ferentiation and interesting findings regarding the results of its mutation, we wanted to study its potential role in psori- asis, which has been proven to be associated precisely with impaired keratinocytes proliferation and differentiation. Materials and Methods The study included 60 patients (21 women and 39 men) with active plaque-type psoriasis, at the mean age of 50±2.34 years and 30 sex- and age-matched volunteers without dermatoses and negative family history of psoriasis. The following exclu- sion criteria from the study were applied: age under 18 years, pregnancy, types of psoriasis other than plaque psoriasis, dietary restrictions and intake of oral medications at least three months prior to the study, application of topical agents at least one month prior to the study, malignancies, and re- nal dysfunction. The severity of psoriatic skin lesions was assessed using the Psoriasis Area and Severity Index (PASI) and was always performed by the same dermatologist in all patients. The study group of patients was divided into three subgroups depending on the severity of their disease: PASI I (PASI <10) - mild psoriasis, PASI II (PASI 10-20) - moderate psoriasis, and PASI III (PASI> 20) - severe psoriasis. Body mass index (BMI) was calculated as weight / height2. Lab- oratory tests, including C-reactive protein (CRP), complete Conclusions: Obtained results point to the probable involvement of GSDMA in psoriasis. GSDMA overexpression may probably lead to keratinocytes hyperproliferation and be responsible for trig- gering inflammation in psoriatic skin. Serum GSDMA could become psoriasis biomarker, whereas urinary GSDMA, not at this point. Original Article | Dermatol Pract Concept. 2024;14(3):e2024177 3 blood count, fasting serum glucose, lipid profile, and mark- ers of liver and kidney function, were performed. The study was approved by the Bioethics Committee of the Medical University of Bialystok (number: APK.002.303.2022 and APK.002.19.2020) and was conducted in accordance with the principles of the Helsinki Declaration. Each participant provided written consent before the study commenced. Serum and Urine Fasting blood samples were taken using vacuum tubes. They were left to clot for 30 minutes before centrifuging for 15 minutes at 2000g. Urine samples were taken as first morning specimens from a mid-stream; they were centrifugated for 10 minutes at 2000g. The obtained serum and urine were stored at -80 °C until further analysis. Laboratory parameters were measured using routine techniques. GSDMA concentrations were measured with an enzyme-linked immunosorbent assay (ELISA) provided by EIAab® (E11790h) with a minimum detectable dose of 0.156-10 ng/ml. The concentrations were assessed by interpolation from calibration curves prepared with standard samples provided by the manufacturer. All the tests were performed by the same person in standardized lab- oratory settings. Tissue Tissue samples were collected from 33 patients with psori- asis and 20 sex- and age-matched volunteers without skin diseases. All participants did not apply any topical agents on the skin at least a month before the biopsy. Biopsies, obtained from the trunk using a 4 mm punch after local anesthesia, included one each from psoriatic plaque and non-lesional skin in patients and one from non-lesional skin in controls performed during the surgical removal of benign skin lesions. Tissue samples were then fixed in 10% buff- ered formalin solution. After preservation, they were embed- ded in the paraffin blocks, and cut into 4 µm sections on silanized slides. The next step was an overnight incubation at 60° C, deparaffinization, and rehydration of tissues. Slides were then incubated with 3% hydrogen peroxide solution to block endogenous peroxidase and with protein block to avoid nonspecific antibody binding. Next, tissues were incu- bated with rabbit polyclonal anti-human GSDMA antibody (HPA023313, dilution 1:50, Clone OTI1, Sigma-Aldrich®) for 30 minutes at room temperature. Then, Post Primary Block and Novolink Polymer were used (Leica Novolink Polymer Detection System®, United States). Protein expres- sion was visualized with Novolink DAB solution and cell nuclei with hematoxylin (Leica Novolink Polymer Detection System®, United States). Positive control of immunostaining was sebaceous cells in normal skin (Figure 1A). The presence of GSDMA was presented using a semi-quantitative method. Intensity and localization of immunostaining were analyzed and defined as follow: low expression – weak/medium staining intensity in stratum corneum of epidermis; medium expression – weak/medium staining intensity in stratum corneum, granulosum and spi- nosum, up to 2/3 of the epidermis; strong expression – strong staining intensity in more than 2/3 of the epidermis or in the whole epidermis. Staining was observed mostly in cytoplasm of epithelial cells, but nuclear staining in cases with strong expression was also noted. Figure 1 (A-L) presents the ex- pression of GSDMA in patients and controls. Statistical Analysis All analyses were performed in GraphPad 9.4 Prism. The normally distributed data were analyzed using a one-way analysis of variance (ANOVA) and shown as mean ± SD. The non-Gaussian data were presented as median (full range) and analyzed using non-parametric Mann–Whitney. The chi-square test of independence was used to assess the relationship between two nominal variables. The correla- tions between the examined parameters were evaluated with Spearman’s rank test. The differences were deemed statisti- cally significant when P < 0.05. Results The basic information on patients and controls is presented in Table 1. We enrolled 60 psoriatic patients (39 men and 21 women) and 30 controls (20 men and 10 women) in total. There was no statistically significant difference between pa- tients and controls in terms of age, sex, or BMI (NS). Serum and Urine Serum and urine were assessed in 60 patients and 30 con- trols. The median GSDMA serum concentration in patients was 0.5437 (0.03–1.407) ng/ml, whereas in the controls it was – 0.3622 (0.031–0.793) ng/ml. The median urinary con- centration of GSDMA in patients was 0.138 (0.012–0.779) ng/ml, whereas in the controls it was – 0.1235 (0.027-0.285) ng/ml. The median ratio between urinary GSDMA and uri- nary creatinine in patients was 0.00295 (0.0005–0.0243), whereas in the controls it was 0.00345 (0.0006–0.0316). The serum concentration (Figure 2A) and absolute uri- nary concentration (Figure 2B) of GSDMA were signifi- cantly higher in psoriatic patients than in controls without skin diseases (P < 0.05), whereas the urinary GSDMA/creat- inine ratio was insignificantly lower (Figure 2C). After the division of patients into three groups depend- ing on psoriasis severity on PASI, GSDMA serum concen- trations were higher in subjects with higher PASI; however, there was no significant difference between the groups (NS) (Figure  3A.). After the division of patients into subgroups depending on the psoriasis duration (Figure 3B) or by sex 4 Original Article | Dermatol Pract Concept. 2024;14(3):e2024177 Figure 1. Immunohistochemical expression of GSDMA in healthy group and patients with psoriasis. Healthy skin – GSDMA weak expression in stratum corneum, also positive staining in the sebaceous glands (A,B); Non-lesional skin (patients with psoriasis) – weak expression in stratum corneum (C,D), medium (E,F) and high (G,H) expression in stratum corneum, granulosum, and spinosum, up to 2/3 of the epidermis; Lesional skin (psoriasis) – medium expression in stratum corneum, granulosum and spino- sum, up to 2/3 of the epidermis (I,J); Lesional skin (psoriasis) – strong expression in more than 2/3 of the epidermis or in the whole epidermis (K,L). Magnifications x 100 and x 400. Original Article | Dermatol Pract Concept. 2024;14(3):e2024177 5 expression, 11 samples had moderate expression, and only one sample had low expression. Among the samples taken from the non-lesional skin of patients, seven samples exhib- ited strong GSDMA expression, 13 samples had moderate expression, and 13 samples had low expression. Among the control group, all samples exhibited low GSDMA samples, and only 1 with strong GSDMA expression. The majority of the samples taken from the psoriatic plaque exhibited strong GSDMA expression, whereas the majority of samples from the healthy skin of controls exhib- ited low GSDMA expression. Strong expression of GSDMA was significantly more prevalent in psoriatic plaques com- pared to non-lesional patients’ skin and healthy skin of con- trols (P < 0.01 and P < 0.001, respectively). Low expression of GSDMA was significantly more prevalent in the healthy skin of controls than in non-lesional patients’ skin and pso- riatic plaques (P < 0.001 and P < 0.01, respectively). There was no sample with moderate expression of GSDMA in healthy controls (Figure 5). After the division of patients according to psoriasis severity on PASI, in subjects with mild psoriasis (PASI I), we observed samples only with low GSMDA expression. The highest num- ber of samples with strong GSDMA expression was found in the subgroup of severe psoriasis (PASI III) (Figure 6). Conclusions We here report on the possible role of GSDMA in psoria- sis. Unfortunately, GSDMA seems to be understudied so far, and the data on its biological role and involvement in other diseases are scarce. That makes our results challenging to interpret at this point. Nevertheless, as for dermatoses, a very recent publication investigated GSDMA in atopic dermatitis (AD). Surprisingly, GSDMA had lower expression in the AD (Figure 3C), there was no significant difference between the groups (NS). After the division of patients according to BMI, there was no significant difference between the subgroups (NS, data not shown). There was no significant correlation between serum con- centration of GSDMA and PASI, BMI, age, sex of patients, or psoriasis duration (NS). Among the laboratory investigations, there was a strong significant negative correlation between GSDMA serum concentration and ALT activity (R = -0.38; P = 0.0026) (Figure 4). Tissue Tissue GSDMA expression was assessed in 33 patients and 20 controls. The presence of GSDMA was presented as low expression (in stratum corneum), moderate expression (in stratum corneum, granulosum, and spinosum, up to 2/3 of the epidermis), or strong expression (in more than 2/3 of the epidermis or in the whole epidermis). Twenty-one samples taken from the psoriatic plaques exhibited strong GSDMA Table 1. The basic information on patients and controls. Parameter Controls (n=30) Psoriatic patients (n=60) Sex (M/F) 20/10 39/21 NS Age [years] 48±2.45 50±2.34 NS Height [cm] 1.75 (1.5-1.9) 1.71 (1.5-1.9) NS Weight [kg] 78.40±2.9 85.43±2.5 NS BMI 25.85±0.77 27.85±0.64 NS NS, non-significant. Figure 2. Serum GSDMA concentration (A), absolute urinary GSDMA concentration (B), and urinary GSDMA/creatinine concentration ratio (C) in patients and controls; serum GSDMA concentration after the division of patients depending on PASI, psoriasis duration, and sex compared to controls. *means a statistically significant difference with P < 0.05. 6 Original Article | Dermatol Pract Concept. 2024;14(3):e2024177 One of the key yet few studies shedding some light on GSDMA role which could be applied in psoriasis is that by Tanaka et al. In the mice with GSDMA3 mutation, they ob- served epidermal hyperplasia [21], which is interesting con- sidering histopathological findings in psoriasis. However, in the opposite experiment on GSDMA knock-out mice, there were no changes in their clinical skin condition [21]. The authors suggested that it might be due to other genes taking over the role of GSDMA and that its biological role emerges when stimulated by external factors [21]. Nevertheless, these observations must be approached with caution because they are made on mice, which have three GSDMA orthologs (GSDMA 1-3), whereas humans have only one [21], so re- sults based on GSDMA3 specifically cannot be directly ex- trapolated on humans, especially GSDMA3, the only gene in which the mutation exhibited epidermal alterations. The authors of the study attempted to explain the mechanism underlying acanthosis since it is not fully clear. They sug- gested that it is the inflammation in the mice’s skin that leads to epidermal hyperplasia [21]. They focused on TGF-β be- cause GSDMA is engaged in TGF-β-mediated apoptosis, and overexpression of TGF-β triggers skin inflammation [21]. TGF-β up-regulates GSDMA and therefore promotes apop- tosis [12]. On the other hand, TGF-β has been investigated in psoriasis, and an elevated concentration of TGF-β has been observed in the plasma and scales of psoriatic patients [23]. In addition, this plasma level was associated with skin lesion severity and decreased after antipsoriatic therapy [23,24]. Another study that attempted to discover the role of GSDMA in the skin was that by Lin et al. Their team ob- served that induction of GSDMA3 expression in mice leads to epidermal hyperplasia and skin inflammation [20]. They concluded that keratinocytes that exhibited GSDMA over- expression suffered from oxidative stress and underwent spontaneous necrosis followed by inflammatory condition lesions than in healthy skin, and GSDMA1/A3-deficiency se- lectively enhanced the Th cells type 2 response. The authors suggested that GSDMA may be involved in AD pathogene- sis due to its influence on keratinocytes differentiation and cornification [22]. Figure 3. The division of patients depending on (A) PASI, (B) psoriasis duration, and (C) gender com- pared to controls. Figure 4. Correlations between serum gasdermin A concentration and basic laboratory parameters. (ALT, alanine transaminase; AST = asparagine transaminase; TG = triglycerides; Chol = total cholesterol; HDL = high-density lipoprotein; LDL = low-density lipoprotein; GLU = fasting glucose; CRP = C-reactive protein; CR = creatinine; GFR = glomerular filtration rate; UAC = uric acid; Urea; WBC = white blood cells; RBC = red blood cells; HGB = hemoglobin; PLT = platelets.). Original Article | Dermatol Pract Concept. 2024;14(3):e2024177 7 psoriatic epidermis [27]. Autophagy promotes high- mobility group box 1 (HMGB-1) secretion in psoriasis and leads to chronically sustained inflammatory condition in this dermatosis [26]. Another piece of evidence justifying this hy- pothesis is that there are polymorphisms in the autophagy gene described which are related to psoriasis [26]. Herein, the data on GSDMA role in the skin are scarce and also sometimes inconsistent. Apparently, GSDMA takes part in cell death in different mechanisms but surely its over- expression exacerbates inflammation. There are also many connections between GSDMA and already recognized links in the epidermis [20]. Oxidative stress plays a major role in psoriasis pathology [25]. Although the data on GSDMA are poor, there are more rationales that could support GSDMA’s engagement in pso- riasis and point to its role in its pathogenesis. Activation of GSDMA leads to stimulation of caspase 3 and further to induction of autophagy [12]. Wang et al. suggested that autophagy is activated in psoriatic epidermis and is prob- ably important in the proliferation and differentiation of keratinocytes in psoriasis [26]. Overexpression of the autophagy-related protein, SQSTM1 has been observed in Figure 5. The expression of GSDMA (strong, moderate, low) depending on the site of biopsy (psoriatic plaque, non-lesional patients’ skin or healthy skin of controls). ***vs low expression with p<0.001, ^^/^^^ vs moderate expression with p<0.01/0.001 respectively, ##/### vs strong expression with p<0.01/p<0.001, respectively. Figure 6. The extent of expression of GSDMA in psoriatic plaque depending on the psoriasis severity in PASI. 8 Original Article | Dermatol Pract Concept. 2024;14(3):e2024177 In our study, we obtained a negative correlation between GSDMA and ALT, which could serve as an interesting start- ing point for more in-depth future studies. Therefore, we can hypothesize that GSDMA may exert a protective influ- ence on the liver. Knorr et al. reviewed the role of pyropto- sis (thus gasdermins) in different liver diseases, but they did not mention any engagement of GSDMA in this matter [29]. On the other hand, GSDMA gene was included in the set of pyroptosis-related genes that have been found useful to as- sess the risk score of hepatocellular carcinoma (HCC) [30]. Apart from research on GSDMA in HCC, we were not able to find any information on its role in liver disorders, so we have no data for comparison with our results. Study limitations include a small, predominantly Cauca- sian sample and a scarcity of relevant GSDMA studies. Our study comprehensively examined the role of GSDMA in psoriasis. We report on its increased concentrations in psoriatic patients’ sera. Moreover, we found its more promi- nent expression in plaque psoriasis compared to non-lesional patients’ skin and healthy skin of subjects without dermato- ses. Our study shows that GSDMA is probably engaged in psoriasis pathogenesis, and its overexpression may probably lead to keratinocytes hyperproliferation and be responsible for triggering inflammation in psoriatic skin. GSDMA serum concentration could be used as its biomarker but not of skin lesion severity. Urinary GSDMA is probably not useful as a biomarker. Considering that the data on GSDMA are sparse and that its role in the skin is unclear, further studies are needed to understand GSDMA function, including in psori- asis. Further research on GSDMA as a potential drug target would be of high value. References 1. Farley E, Menter A. Psoriasis: Comorbidities and associations. G. Ital. Dermatol. Veneorol. 2011;146:9–15. 2. Hirotsu C, Rydlewski M, Araújo MS, et al. Sleep loss and cyto- kines levels in an experimental model of psoriasis. PLoS ONE. 2012; 7:e51183. 3. Lanna C, Mancini M, Gaziano R, et al. Skin immunity and its dysregulation in psoriasis. Cell Cycle. 2019;18:2581-2589. 4. Rendon A, Schäkel K. Psoriasis Pathogenesis and Treatment. Int J Mol Sci. 2019; 20:1475. 5. Nabieva K, Vender R. Quality of Life and Body Region Affected by Psoriasis: A Systematic Review. Actas Dermosifiliogr. 2023; 114:33-38. 6. Saeki H, Kanai Y, Murotani K, et al. Work productivity in real-life employed patients with plaque psoriasis: Results from the ProLOGUE study. J Dermatol. 2022;49:970-978. 7. Information about psoriasis, available at: https://www.psoriasis .org/about-psoriasis/ accessed on August 7, 2023. 8. Armstrong AW, Read C. Pathophysiology, Clinical Presenta- tion, and Treatment of Psoriasis: A Review. JAMA. 2020; 323: 1945-1960. in the pathogenesis of psoriasis. We must take into consider- ation, though, that almost all available studies that focused on the role of GSDMA particularly in the skin were per- formed on mice, not humans. The only experiment on psori- atic skin tissue, albeit on a very small sample size, examined the expression of GSDMA gene, present in all epidermal layers but most prominent in the stratum corneum [28]. We were not able any other study using immunohistochemistry in psoriatic tissue to assess the role of gasdermins. Based on the significantly higher GSDMA serum con- centration in psoriatic patients and its more prominent ex- pression in plaque psoriasis compared to subjects without psoriasis, we could certainly suspect that it actually plays a role in psoriasis, and its serum concentration could become its biomarker. Overexpression of GSDMA in plaque psoriasis compared to non-lesional skin and healthy skin of controls seems consistent with findings by Lin et al. [20]. Its pres- ence may probably lead to keratinocytes hyperproliferation and be responsible for triggering inflammation in psoriatic skin. However, the exact mechanism in psoriasis remains un- certain. On the other hand, considering the involvement of GSDMA in several types of cell death, it cannot be fully ruled out that GSDMA may be compensatively elevated to lead the cells toward apoptosis – which requires further research. As for the urine, it is an ideal fluid to collect for screening since it is easy and painless to donate. Considering differ- ent kidney functions in patients, we presented our results as absolute urinary concentrations and with creatinine ratio to obtain objective results. Unfortunately, we did not observe significant differences between patients and controls in terms of urinary GSDMA/creatinine ratio, which would be a more objective parameter than absolute urinary concentration, so urine probably cannot be used for biomarker detection in this group of patients. We are not familiar with any other study assessing urinary GSDMA. Serum GSDMA was not directly correlated with psori- asis severity in PASI, nor is there any significant difference between the PASI subgroups regarding its concentration, although serum GSDMA concentrations were higher in pa- tients with more severe psoriasis and in such subjects, there was higher expression of GSDMA in psoriatic plaque ob- served. Instead, patients with mild psoriasis had only low ex- pression. 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