Analysis of Clinical and Genetic Factors of Obesity and Psoriasis Concomitance-The Influence of Body Mass Composition, Prevalence of Mood Disorders, Environmental Factors and FTO Gene Polymorphisms (rs9939609, rs1558902).

This study aimed to comprehensively analyze the problem of overweight and obesity among psoriatic patients by investigating the influence of body mass composition, anhedonia and depression, environmental factors and FTO gene polymorphisms. METHODS: The study enrolled 30 overweight or obese adult patients with chronic plaque psoriasis and 30 overweight or obese volunteers (northern Poland region, Caucasian population). Mood disorders, body mass composition by using bioelectrical impedance analysis (BIA) and FTO gene polymorphisms (rs9939609, rs1558902) by tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) were assessed. RESULTS: Results revealed significantly higher visceral adipose tissue levels in psoriatic patients (5.23 ± 2.29 [L] vs. 3.41 ± 1.86 [L]), p = 0.001), especially among men, along with elevated rates of moderate and severe depression (26.67% vs. 6.67% and 13.33% vs. 3.33%, p = 0.048 respectively). Additionally, FTO gene polymorphisms correlated with waist-hip ratio differences in both groups. CONCLUSIONS: The study highlights the importance of evaluating body composition beyond body mass index, recognizing its influence on psoriasis and associated conditions like depression. The FTO gene may serve as a potential genetic link between psoriasis and obesity, warranting further research for validation. Adiposity emerges as a key and modifiable risk factor, underscoring the clinical implications of body composition complexities in psoriasis management.

An Observational Study of 147 Psoriasis Patients: Overweightness and Obesity as a Significant Clinical Factors Correlated with Psoriasis.

Background and Objectives: Psoriasis is a common, chronic, and immune-mediated inflammatory skin disease recognized to lead to a wide range of comorbid disorders, mainly obesity. The study aimed to evaluate the problem of overweightness and obesity among psoriasis patients in the context of their prevalence and influence on the disease course. Materials and Methods: The study group encompassed 147 adult patients with plaque psoriasis. Results: The prevalences of overweightness (39.46%) and obesity (37.41%) demonstrated in the study showed the strong predisposition of psoriatic patients for abnormal body mass. The vast majority (77%) of subjects with psoriatic arthritis were overweight or obese. The results of the correlation analysis revealed the significant impacts of overweightness and obesity, as defined by the BMI index, on modifying the severity of psoriasis (as assessed by the PASI with a correlation coefficient of R = 0.23, p = 0.016; and BSA values with a correlation coefficient of R = 0.21, p = 0.023), particularly in contrast to patients with a normal body mass. Conclusions: Overweightness and obesity constitute a major health burden among psoriatic patients, influencing the disease course and severity. Enhanced understanding of the phenomenon may directly translate into improving disease management and overall patient care.

The Associations of Single Nucleotide Polymorphisms of the COL3A1, COL6A5, and COL8A1 Genes with Atopic Dermatitis.

The pathophysiology of atopic dermatitis (AD) is complex, multifactorial, and not fully understood. Genes encoding collagens, the most abundant proteins in the extracellular matrix (ECM), may play a potential role in the pathogenesis of AD. Our study aimed to estimate the associations between Col3A1/rs1800255, Col6A5 /29rs12488457, and Col8A1/rs13081855 polymorphisms and the occurrence, course, and features of AD in the Polish population. Blood samples were collected from 157 patients with AD and 111 healthy volunteers. The genotype distribution of the investigated collagens genes did not differ significantly between the AD and control subjects (p > 0.05). The AA genotype of Col3A1/rs1800255 was significantly associated with the occurrence of mild SCORAD (OR = 0.16; 95% Cl: 0.03-0.78; p = 0.02) and mild pruritus (OR = 18.5; 95% Cl: 3.48-98.40; p = 0.0006), while the GG genotype was significantly associated with severe SCORAD (OR = 6.6; 95% Cl: 1.23-32.35; p = 0.03). Regarding Col6A5/29rs12488457 polymorphism, the average SCORAD score was significantly lower in the group of patients with genotype AA than in patients with the AC genotype (39.8 vs. 53.4; p = 0.04). Nevertheless, both average SCORAD scores were high, and represent the moderate and severe grades of the diseases, respectively. The single nucleotide polymorphisms (SNPs) of COL3A1/ rs1800255 and Col6A5/29rs12488457 seem to be associated with AD courses and symptoms, suggesting new disease biomarkers. The modulation of collagens, the major component of the ECM, may serve as a therapeutic target of AD in the future.

Assessment of the Potential Role of Selected Single Nucleotide Polymorphisms (SNPs) of Genes Related to the Functioning of Regulatory T Cells in the Pathogenesis of Psoriasis.

Recent studies have indicated a key role of the impaired suppressive capacity of regulatory T cells (Tregs) in psoriasis (PsO) pathogenesis. However, the genetic background of Treg dysfunctions remains unknown. The aim of this study was to evaluate the association of PsO development with selected single nucleotide polymorphisms (SNPs) of genes in which protein products play a significant role in the regulation of differentiation and function of Tregs. There were three study groups in our research and each consisted of different unrelated patients and controls: 192 PsO patients and 5605 healthy volunteers in the microarray genotyping group, 150 PsO patients and 173 controls in the ARMS-PCR method group, and 6 PsO patients and 6 healthy volunteers in the expression analysis group. The DNA microarrays analysis (283 SNPs of 57 genes) and ARMS-PCR method (8 SNPs in 7 genes) were used to determine the frequency of occurrence of SNPs in selected genes. The mRNA expression of selected genes was determined in skin samples. There were statistically significant differences in the allele frequencies of four SNPs in three genes (TNF, IL12RB2, and IL12B) between early-onset PsO patients and controls. The lowest p-value was observed for rs3093662 (TNF), and the G allele carriers had a 2.73 times higher risk of developing early-onset PsO. Moreover, the study revealed significant differences in the frequency of SNPs and their influence on PsO development between early- and late-onset PsO. Based on the ARMS-PCR method, the association between some polymorphisms of four genes (IL4, IL10, TGFB1, and STAT3) and the risk of developing PsO was noticed. Psoriatic lesions were characterized with a lower mRNA expression of FOXP3, CTLA4, and IL2, and a higher expression of TNF and IL1A in comparison with unaffected skin. In conclusion, the genetic background associated with properly functioning Tregs seems to play a significant role in PsO pathogenesis and could have diagnostic value.

Considerations of the Genetic Background of Obesity among Patients with Psoriasis.

Psoriasis comorbidities may emerge from pleiotropic mechanisms, including common proinflammatory pathways, cellular mediators or genetic predisposition. Obesity is considered to be an independent risk factor of psoriasis, which may influence the severity of the disease and its early onset, decrease patients' quality of life, alter response to psoriasis therapies and affect morbidity by reduced life expectancy due to cardiovascular events. Although novel approaches, including genetic techniques, have provided a wide range of new research, there are still scarce studies elaborating on the common genetic background of psoriasis and obesity. The aim of this study was to present and evaluate a possible common genetic background of psoriasis and concomitant increased body mass based on the review of the available literature.

Serum levels and single nucleotide polymorphisms of the interleukin-33 gene in atopic dermatitis.

Introduction: Interleukin 33 (IL-33) is considered significant in the pathogenesis of atopic dermatitis (AD). Aim: To determine the correlation between the serum levels of IL-33 and single nucleotide polymorphisms of its gene in the -9894 T/C (rs1929992) and -11877 C/T (rs10975519) loci and the course of AD. Material and methods: The study group consisted of 191 patients with AD and 168 controls. Results: The TT genotype appeared to be most frequent in patients with severe pruritus (OR = 6.69, 95% CI: 1.24-35.99, p = 0.01). Conclusions: The results of our study are particularly important in the light of personalized medicine and might significantly contribute to further studies in this field.

Chemokine Profile in Psoriasis Patients in Correlation with Disease Severity and Pruritus.

Psoriasis (PsO) is a chronic, immune-mediated, inflammatory skin disease associated in most cases with pruritus. Chemokines seem to play a significant role in PsO pathogenesis. The aim of the study was to analyse serum concentrations of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, CCL5/RANTES, CCL17/TARC, CCL18/PARC, CCL22/MDC and CXCL8/IL-8, and their correlation with PsO severity and pruritus intensity. The study included 60 PsO patients and 40 healthy volunteers. Serum concentrations of six (CCL2/MCP-1, CCL3/MIP-1α, CCL5/RANTES, CCL17/TARC, CCL18/PARC and CCL22/MDC) out of eight analysed chemokines were significantly elevated in PsO patients; however, they did not correlate with disease severity. The serum level of CCL5/RANTES was significantly higher in patients with the psoriasis area and severity index (PASI) ≥ 15 (p = 0.01). The serum concentration of CCL17/TARC correlated positively with pruritus assessed using the visual analogue scale (VAS) (R = 0.47; p = 0.05). The study indicated CCL17/TARC as a potential biomarker of pruritus intensity in PsO patients. Chemokines appear to be involved in the development of PsO systemic inflammation. Further detailed studies on the interactions between chemokines, proinflammatory cytokines and immune system cells in PsO are required to search for new targeted therapies.

The Analysis of a Genome-Wide Association Study (GWAS) of Overweight and Obesity in Psoriasis.

There is evidence that the concomitance of psoriasis and obesity may originate from the interplay between multiple genetic pathways and involve gene−gene interactions. The aim of this study was to compare the genetic background related to obesity among psoriatic patients versus healthy controls by means of a Genome-Wide Association Study (GWAS). A total of 972 psoriatic patients and a total of 5878 healthy donors were enrolled in this study. DNA samples were genotyped for over 500,000 single nucleotide polymorphisms (SNPs) using Infinium CoreExome BeadChips (Illumina, San Diego, CA, USA). Statistical analysis identified eleven signals (p < 1 × 10−5) associated with BMI across the study groups and revealed a varying effect size in each sub-cohort. Seven of the alternative alleles (rs1558902 in the FTO gene, rs696574 in the CALCRL gene, as well as rs10968110, rs4551082, rs4609724, rs9320269, and rs2338833,) are associated with increased BMI among all psoriatic patients and four (rs1556519 in the ITLN2 gene, rs12972098 in the AC003006.7 gene, rs12676670 in the PAG1 gene, and rs1321529) are associated with lower BMI. The results of our study may lead to further insights into the understanding of the pathogenesis of obesity among psoriatic patients.

Interleukin-31 is overexpressed in skin and serum in cutaneous T-cell lymphomas but does not correlate to pruritus.

Introduction: Cutaneous T-cell lymphomas (CTCL) are malignant lymphoproliferative disorders accompanied by persistent pruritus. Pruritogenic role of interleukin-31 (IL-31) has been studied extensively and was proven in atopic dermatitis (AD), while its role in CTCL is still rather vague. Aim: To investigate IL-31 serum level along with IL-31, IL-31 receptor α (IL-31RA) and oncostatin M receptor ß (OSMR) skin expression in CTCL and compare it to controls: AD and healthy volunteers. Material and methods: The level of IL-31 in serum was measured using ELISA, while IL-31 and receptors' expression in the skin were measured using immunohistochemistry and correlated with the stage of disease and pruritus severity. Results: Expression of IL-31 and IL-31 receptor in serum and skin were significantly higher in CTCL and AD in comparison to healthy controls. No significant correlation between the IL-31 serum level and pruritus severity in CTCL patients was found. There was also no correlation between IL-31/IL-31RA/OSMR expression in the skin and CTCL pruritus, while IL-31 and IL-31RA in CTCL skin negatively correlated with the stage of disease. Conclusions: Our data indicate that IL-31 does not play a crucial role in pruritus in CTCL but it is rather involved in the pathogenesis of the disease. It seems that IL-31 plays an essential role in the pruritus pathomechanism that is unique to AD.

Chronic Plaque Psoriasis in Poland: Disease Severity, Prevalence of Comorbidities, and Quality of Life.

The epidemiology of psoriasis has not been widely assessed in Polish population so far. This study aimed to investigate psoriasis epidemiological situation by evaluating disease course and severity, management, comorbidities, environmental factors, and knowledge about this disorder among psoriatic patients in Poland. A cross-sectional cohort population-based study enrolled 1080 psoriatic patients and 1200 controls. The mean age of psoriasis onset was 27.6 years; 78.24% had type I psoriasis. Positive family history of psoriasis was reported in 44.81% of patients, whereas itch was reported in vast majority of patients (83.33%). Based on PASI score moderate psoriasis was the most common in studied group (mean 12.63 ± 9.33, range 0−67.2). The DLQI score (12.01 ± 7.41, range 0−30.0) indicated a very large effect of psoriasis on the quality of life. Hypertension was the most prevalent comorbidity (33.80%), followed by obesity (16.85%) and dyslipidemia (11.85%). Stress was the foremost cause of disease exacerbation (66.20%); however, infections (44.07%) and seasonal changes (45.09%) had also an impact on the course of psoriasis. Psoriatic patients were more often smokers (37.59%) vs. general population (27.50%; p < 0.0001). In conclusion, epidemiological studies help clinicians in better disease and patient understanding, which may translate into better management and patient compliance.

Translation, cross-cultural adaptation and validation of the vitiligo-specific health-related quality of life instrument (VitiQoL) into Polish.

INTRODUCTION: Vitiligo is an acquired chronic depigmenting disorder of the skin, predominantly asymptomatic. Although vitiligo does not cause direct physical impairment, it is commonly believed that it can produce an important psychosocial burden. AIM: To translate, cross-culturally adapt and validate the vitiligo-specific health-related quality of life instrument (VitiQoL) into Polish. MATERIAL AND METHODS: The study was conducted online on 97 patients with vitiligo from our private outpatient departments in Gdynia and Gdansk, Poland from May 2018 to December 2019. RESULTS: There was a significant correlation between VitiQoL and DLQI (r = 0.90, p < 0.001) and also between VitiQoL-PL and subjects' assessment of the severity of their disease (r = 0.94, p < 0.001). We also found a good correlation between the total DLQI and subjects' assessment of the severity of their disease (r = 0.87, p < 0.001). CONCLUSIONS: The physicians treating this disease still do not have a specific instrument for assessing patients' QoL in Poland. They have to administer other non-vitiligo specific questionnaires to do so. A Polish version of a specific index for estimating quality of life of patients with vitiligo was validated and implemented through an online survey.

Significance of interleukin-31 (IL-31) gene polymorphisms and IL-31 serum level in psoriasis in correlation with pruritus.

INTRODUCTION: Interleukin-31 (IL-31) impact on the development and clinical presentation of psoriasis as well as pruritus has not been widely investigated so far. AIM: To analyse IL-31 -1066G/A and -2057G/A promoter gene polymorphisms as well as serum IL-31 level and their correlation with severity of psoriasis and pruritus in the population of northern Poland. MATERIAL AND METHODS: The study included 300 psoriasis patients and 186 healthy volunteers. The polymorphisms were analysed using amplified refractory mutation system - polymerase chain reaction (ARMS-PCR) method. Serum levels of IL-31 were measured using the enzyme-linked immunosorbent assay (ELISA) test. RESULTS: The -1066 AA genotype of the IL-31 gene was statistically more frequent in patients and it increased the risk of psoriasis (OR = 1.80; p = 0.04). The GG genotype as well as G allele of the IL-31 -2057 gene polymorphism were rarely observed in psoriasis and were associated with a decreased risk of the disease (OR = 0.6, p = 0.007 and OR = 0.7, p = 0.01, respectively). Serum levels of IL-31 were significantly elevated in psoriasis patients (p < 0.000001), however, they did not correlate with the studied polymorphic variants of the IL-31 gene, severity of psoriasis, disease onset, presence of psoriatic arthritis and pruritus intensity. CONCLUSIONS: Distinct IL-31 promoter gene polymorphisms may be involved in psoriasis development. It seems that serum concentration of IL-31 may not be a reliable marker of psoriatic pruritus.

FOXP3 and CTLA-4 genetic variants' influence on the susceptibility and clinical course of basal cell carcinoma.

INTRODUCTION: The pathogenesis of basal cell carcinoma (BCC) is multifactorial and not fully elucidated. Previous studies showed that behaviour of the tumour may be influenced by the immune system and identified CD4+CD25+FoxP3+ regulatory T cells (Tregs) as dominant immune cells in BCC microenvironment. The function and development of Tregs is regulated by FOXP3, encoding transcription factor Forkhead box P3. FOXP3 regulates transcription of many genes, including up-regulation of cytotoxic lymphocyte-associated antigen-4 gene (CTLA-4). Expressed on Tregs, CTLA-4 interacts with antigen-presenting cells to inhibit T-cell activation. AIM: To investigate the role of two polymorphisms (rs3761548 and rs2232365) of FOXP3 and CTLA-4 polymorphism (rs5742909) in BCC patients from northern Poland. MATERIAL AND METHODS: We analysed 280 unrelated patients with BCC of mean age 70.93 ±11.53 (70.54 ±12.55 women, 71.38 ±10.26 men) and 200 healthy, unrelated age- and sex-matched volunteers. RESULTS: The differences in the occurrence of BCC between genotypes and alleles of the analysed polymorphisms were not statistically significant. In the studied group, the presence of the CC genotype in CTLA-4 rs5742909 polymorphism was statistically more frequent in patients with multiple BCCs. CONCLUSIONS: It seems that the analysed FOXP3 and CTLA-4 polymorphisms do not influence the BCC susceptibility. CTLA-4 rs5742909 polymorphism may influence the susceptibility to multiple BCCs.

Modulation of dermal equivalent of hypothalamus-pituitary-adrenal axis in mastocytosis.

INTRODUCTION: Mastocytosis is a rare disease characterized by abnormal growth and accumulation of tissue mast cells (MC) in one or more organ systems and is classified as being either cutaneous mastocytosis (CM) or systemic mastocytosis (SM). In the pioneer studies of Slominski's group, a fully functional hypothalamic-pituitary-adrenal axis equivalent has been discovered in various tissues, including skin. AIM: In the present study we investigated potential involvement of hypothalamus-pituitary-adrenal (HPA) cutaneous equivalent in ongoing mastocytosis. MATERIAL AND METHODS: The expression of HPA elements: CRH, UCN1, UCN2, UCN3, CRHR1, POMC, MC1R, MC2R and NR3C1 was assessed for their mRNA level in skin biopsies of adult patients with mastocytosis and healthy donors (n = 16 and 19, respectively), while CRH, UCN1, CRHR1, ACTH and MC1R were selected for immunostaining assay (n = 13 and 7, respectively). The expression of CRH receptor 1 (CRHR1) isomers was investigated by RT-PCR. The ELISA was used for detection of cortisol, CRH, UCN and ACTH in the serum. RESULTS: The decrease in the expression of HPA element of skin equivalent was observed on both mRNA and protein levels, however quantification of immunohistochemical data was impeded due to melanin in epidermis. Furthermore, we observed infiltration of dermis with HPA elements overexpressing mononuclear cells, which is in the agreement with an in vitro study showing a high expression of HPA elements by mast cells. CONCLUSIONS: Taken together, it was confirmed that the expression elements of HPA was modulated in mastocytosis, thus the potential involvement of general and local stress responses in its pathogenesis should be postulated and further investigated.

-2518A/G polymorphism of monocyte chemotactic protein 1 (MCP-1/CCL2) is associated with cutaneous mastocytosis.

INTRODUCTION: Mastocytosis is a rare heterogeneous disease associated with pathological accumulation of mast cells (MCs) in one or more organs. The disease may be limited to the skin (cutaneous mastocytosis - CM), or present an internal organ involvement (systemic mastocytosis - SM). Pathophysiology of the disease is not well established. However altered proliferation, differentiation and chemotaxis of MC may play an essential role in the development of the disease. The monocyte chemotactic protein 1 (MCP-1/CCL2) may be one of the factors responsible for MCs migration to the skin and other organs. AIM: To analyse the frequency of biallelic A/G polymorphisms at position -2518 in the promoter of the MCP-1 gene and compare the serum level of MCP-1 in patients with both forms of mastocytosis and the healthy control group. MATERIAL AND METHODS: Using ARMS-PCR methods we analysed -2518A/G polymorphisms in the promoter region of the MCP-1 gene in 127 mastocytosis patients (95 CM and 32 SM), and 160 healthy controls. Additionally, the MCP-1 serum level was detected with ELISA technique in 70 patients and 40 controls. RESULTS: We have found that CM patients have more frequently the GG genotype of the MCP-1 gene (p = 0.01) in comparison to SM patients and controls. The GG genotype was more frequent in children than in adults (p = 0.02). The MCP-1 serum level was higher in SM patients than in CM patients and controls. CONCLUSIONS: Results of this study indicate that cutaneous mastocytosis could be associated with the -2518 A/G MPC-1 gene polymorphism.

Efficacy, quality of life, and safety of methotrexate versus interferon in head-to-head treatment in advanced stages of mycosis fungoides and Sezary syndrome. Prospective trial (NCT02323659).

Introduction: ESMO guidelines recommend interferon (IFN) and methotrexate (MTX) as first-line systemic therapies in mycosis fungoides (MF) and Sezary syndrome (SS). Aim: A prospective, head-to-head trial comparing the efficacy and safety of INF-α and MTX as first-line treatment in MF/SS patients. Material and methods: Forty-three patients were enrolled in the trial. The response to treatment and side effects were assessed. Study variables included mSWAT, DLQI, and VAS scores. Results: The response rate in stage IV including SS was significantly higher in the IFN-α group than in the MTX group (100% vs. 40%; p = 0.03, respectively). No significant differences were found in response rate in stage IIB and III between treatment groups. Patients treated with IFN-α had significantly shorter time to achieve response (TTR). Significantly fewer in the IFN-α group experienced adverse events (AE) in comparison to patients treated with MTX (81% vs. 45%; p = 0.02). There was no statistically significant difference between both groups in terms of time to progression (TTP), progression-free survival (PFS), time on treatment (ToT), and time to next treatment (TTNT). The improvement in quality of life and reduction of pruritus was comparable in both treatment groups. Conclusions: The obtained data suggest that the efficacy of IFN-α as first-line treatment in advanced stage (IV) MF and SS is significantly better than MTX. IFN-α presented significantly better safety and tolerability and shorter TTR than MTX. However, the results should be interpreted with caution due to scarce study groups.

The polymorphisms of IL-6/STAT3 signaling pathway may contribute to cutaneous T-cell lymphomas susceptibility.

IL-6/STAT3 signaling pathway has been suggested to play a role in CTCL pathogenesis. Polymorphisms in STAT3 signaling pathway-related genes might be a risk factor for CTCL. However, the exact role of inherited gene polymorphisms of IL-6 and STAT3 in the pathogenesis of CTCL is still not fully understood. The aim was to examine whether IL-6 cytokine and polymorphisms of IL-6 and STAT3 gene are associated with CTCL susceptibility, stage of disease and pruritus intensity. We compared the IL-6 serum level and the frequency of selected single nucleotide polymorphisms of IL-6 and STAT3 in 106 CTCL and 198 control group using polymerase chain reaction with sequence-specific primers method and ELISA. We have found that serum IL-6 level in CTCL patients was significantly higher than in healthy controls (p < 0.05). We also demonstrated that two genotypes, CC of IL-6 and GG of STAT3, were overexpressed in CTCL patients compared to healthy controls, and that they increase the risk of malignancy development (OR = 1.8, p = 0.04 for IL-6 and OR 2.53, p = 0.0064 for STAT3). Moreover, the GG genotype of STAT3 polymorphism seems to be associated with lack of pruritus or mild pruritus in CTCL patients. Our results indicate that IL-6 is involved in pathogenesis of CTCL but not pruritus. Moreover, CC of IL-6 and GG genotype of STAT3 genes might be considered as the risk factor for development of CTCL.

Mapping signal transducer and activator of transcription (STAT) activity in different stages of mycosis fungoides and Sezary syndrome.

BACKGROUND: Deregulation of signal transducer and activator of transcription (STAT) signaling is known to participate in the pathogenesis of cutaneous T-cell lymphomas (CTCLs). However, published results regarding STAT expression in different stages of CTCLs are conflicting. The aim of the study was to define the pattern of STAT expression in skin and detect any differences between pruritic and nonpruritic patients but also different stages of disease. METHODS: Thirty-nine skin biopsies from CTCL patients and 24 biopsies from healthy volunteers were taken. Immunohistochemical staining for STAT 3, 5a, 5b, and 6 was performed in formalin-fixed paraffin-embedded sections of mycosis fungoides (MF) and Sezary syndrome (SS) specimens. RESULTS: We found increased expression of STAT proteins in CTCL: MF and SS skin in comparison to the control group. STAT5 but also STAT6 and to a lesser extent STAT3 seems to be constitutively activated in MF and SS. Moreover, also downregulation of STAT5b protein in advanced-stage CTCL appears to contribute to its pathogenesis. There were no significant associations between expression of STATs and pruritus severity. CONCLUSIONS: Our results confirm the possible pathogenetic role of STATs in CTCL. STATs seem to be a promising target for new effective therapeutic agents in CTCL.

Interleukin-33 polymorphisms and serum concentrations in mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) skin lesions are characterized by low-grade inflammation, which may be sustained by proinflammatory cytokines as probably interleukin-33 (IL-33). We compared serum concentrations of IL-33 and its receptor ST2 and the frequency of selected IL-33 single nucleotide polymorphisms (SNPs) between patients with MF and healthy controls. METHODS: In 88 patients with MF and 66 healthy controls, we analyzed SNPs in the 9894 and 11877 loci of the IL-33 gene. Moreover, we measured serum concentrations of IL-33 and its receptor ST2. RESULTS: There were no statistically significant differences in the frequencies of both IL-33 SNPs between patients and controls. Compared with controls, patients with MF had similar IL-33 serum concentrations (P = 0.71) but significantly increased ST2 concentrations (P < 0.001). Patients in MF-IA stage had significantly lower ST2 serum concentrations than those with the remaining MF stages (P = 0.002). The studied variables were not related to pruritus severity. Patients with the C(+) IL-33 11877 SNP had lower ST2 serum concentrations than patients with the C(-) 11877 SNP (P = 0.043). CONCLUSIONS: It was published before that the knockout of the ST2 gene after injection of IL-33 is associated with a reduced inflammatory reaction in the skin, as well as that IL-33 plays a role in allergic and neoplastic disorders. Concerning the difference in ST2 concentration between control and MF group, and C IL-33 11877 SNP possibly influencing the ST2 concentration, the role of IL-33/ST2 signaling, needs further studies.

STAT3 polymorphisms and IL-6 polymorphism are associated with the risk of basal cell carcinoma in patients from northern Poland.

Basal cell carcinoma (BCC) environment consists of stromal and inflammatory cells which produce variety of cytokines, chemokines and growth factors that may affect tumor behavior. One of the cytokines suggested to be involved in the pathogenesis of BCC is IL-6, which is the upstream element of IL-6/JAK/STAT3 pathway. The correlation between polymorphisms of the genes related to this pathway and cancer risk/prognosis have been previously investigated in several neoplasia, but available data concerning BCC are scarce. In the present study, rs1800795 (-174 G/C) IL-6 gene polymorphism and two polymorphisms in the STAT3 gene, namely rs2293152 (intron 11, C/G) and rs4796793 (-1697, C/G) were assessed in relation to the BCC risk and clinical course. Additionally, IL-6 serum level was assessed in relation to IL-6 genotype and clinical variables. The study included 254 unrelated patients with BCC and of mean age 70.39 ± 11.43 (69.83 ± 12.32 women, 71.03 ± 10.31 men) and 198 healthy, unrelated age- and sex-matched volunteers. IL-6 and STAT3 polymorphisms were analyzed using polymerase chain reaction with sequence-specific primers (SSP-PCR). Serum concentration of IL-6 was measured using the ELISA test. We have found that the presence of C allele in rs1800795 IL-6 gene polymorphism was associated with increased risk of BCC (aOR 1.86; 95% CI 1.22-2.84; p = 0.004). The presence of CC genotype in STAT3 rs2293152 polymorphism was associated with increased BCC risk in recessive model analysis (aOR 3.94; 95% CI 1.59-9.77; p = 0.003). In contrast, the presence of GC genotype in overdominant model was associated with decreased risk of BCC (aOR = 0.24; 95% CI 0.12-0.49; p < 0.0001). The presence of C allele in STAT3 rs2293152 polymorphism was associated with increased risk of BCC (aOR 1.31; 95% CI 1.01-1.69; p = 0.04). The presence of GG genotype in STAT3 rs4796793 polymorphism was associated with increased BCC risk in recessive model analysis (aOR 3.66; 95% CI 1.33-10.10; p = 0.012). The presence of G allele in STAT3 rs4796793 polymorphism was associated with increased risk of BCC (aOR 1.59; 95% CI 1.01-2.49; p = 0.04). IL-6 serum level positively correlated with the tumor size.