Sodium-Glucose Cotransporter 2 Inhibitors During Cancer Therapy: Benefits, Risks, and Ongoing Clinical Trials.

PURPOSE OF REVIEW: The goal of this paper is to summarize the data pertaining to the use of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) for the prevention of cardiotoxicity in patients receiving anthracyclines for cancer treatment. We discuss the potential efficacy of this class of medications, incorporating insights from existing literature and ongoing studies. RECENT FINDINGS: SGLT2i are a class of medications which were initially developed for treatment of Type 2 diabetes and later extended to treat heart failure with reduced and preserved ejection fraction regardless of diabetes status. There remains a need for effective and safe treatments to preventing cardiotoxicity in anthracycline-treated patients. It has been proposed that SGLT2i may provide protection against the cardiotoxic effects of anthracyclines. Some of the proposed mechanisms include beneficial metabolic, neurohormonal, and hemodynamic effects, renal protection, as well as a decrease in inflammation, oxidative stress, apoptosis, mitochondrial dysfunction and ion homeostasis. There is emerging evidence from basic science and observational studies that SGLT2i may play a role in the prevention of chemotherapy-induced cardiotoxicity. Randomized controlled trials are needed to conclusively determine the role of SGLT2 inhibitors as a cardioprotective therapy in patients receiving anthracyclines for the treatment of cancer.

Therapeutic Approach in Pigmented Purpuric Dermatoses-A Scoping Review.

Pigmented purpuric dermatoses (PPD) encompass a group of chronic skin conditions characterized by the presence of petechiae, purpura, and pigmentation changes. While generally benign, these dermatoses can be persistent and aesthetically bothersome. Key clinical features include red to brownish patches with a distinctive "cayenne pepper" appearance, predominantly localized on the lower extremities, particularly the shins. Subtypes include Schamberg disease, Majocchi's disease, Gougerot-Blum disease, Ducas and Kapetanakis pigmented purpura, and lichen aureus. Diagnosis relies primarily on clinical evaluation of skin lesions, with biopsy as a confirmatory tool. Although the exact cause of PPD remains unclear, capillary fragility and red blood cell extravasation are implicated. Treatment strategies for PPD aim to alleviate symptoms, considering the generally benign and chronic nature of the condition. As there is no standardized treatment, various methods with varying efficacy are employed. After searching SCOPUS and PubMed databases, we assessed 42 original articles to present current knowledge regarding therapy of PPD. This review will compare treatment approaches specifically in Schamberg disease and other manifestations of pigmented purpuric dermatoses.

Analysis of the IgG subclass profile and IgG sum-total discrepancy in COVID-19 convalescent plasma donors: A single-centre prospective cohort study.

INTRODUCTION: Although IgG1 and IgG3 have been shown to be the dominant subclasses in the acute phase of SARS-CoV-2 infection, little is known about the distribution of IgG subclasses during the recovery phase of COVID-19. The aim of the study was to analyze the profile of IgG subclasses in COVID-19 convalescent plasma donors. METHODS: A total of 36 convalescent plasma donors were included in the analysis. IgG and IgG subclass levels were measured using a nephelometric assay in plasma samples obtained directly from the plasma container. RESULTS: Although there was no significant difference in the concentration of IgG subclasses between the study and control groups, the contribution of IgG1 to the total IgG pool between the study and control groups was statistically significant (p = 0.0478). In addition, there was a discrepancy between the total IgG and IgG sum values in the study group, exceeding 15 % in 19,4 % of samples (n = 7), while in the control group no samples with a sum/ total IgG difference > 15 % were observed. CONCLUSIONS: The selective affinity of the IgG1 subclass for the polyclonal anti-IgG reagent may interfere with the determination of total IgG and should be considered when interpreting the results of enzyme immunoassays DATA AVAILABILITY: The data that support the findings of this study are available on request from the corresponding author.

The Impact of Pathogen Reduction on Total IgG and IgG Subclass Profiles of Convalescent Plasma.

Introduction: In case of newly emerging pathogens, convalescent plasma (CP) is often the only early available treatment option. It has been shown that different IgG subclasses contribute differently to CP neutralizing activity. As CP donors often have a risk profile like first-time donors, especially with respect to window-period viral transmission, pathogen reduction (PR) could mitigate that risk. The aim of our study, especially in the light of potential future pandemics, was to evaluate the impact of commercially available PR technologies on total IgG and IgG subclasses quantity and distribution in CP using COVID-19 CP (CCP) as surrogate for CP in a side-by-side comparison approach. Methods: 36 apheresis CCP donations were allocated to three study groups and a side-by-side assessment of the potential impact of amotosalen (AS)/UVA treatment compared to a riboflavin (RB)/UVB treatment, AS against methylene blue (MB) treatment, and RB against MB treatment on the quantity of IgG and IgG subclasses with a nephelometric analyzer was performed. Results: IgG subclass distributions were not significantly changed post PR treatment with all three technologies. There was also no significant difference in the median loss of concentration for IgG1 and IgG2 between the three technologies. We recognized a non-significant trend of a higher IgG4 median loss post RB treatment compared to post AS and MB treatment, respectively. Conclusion: Although the three commercially available PR systems do not significantly alter the distribution of IgG subclasses, we detected a non-significant trend of higher IgG4 loss after RB treatment. The potential impact of that finding needs further investigation.

The Detectability of the Viral RNA in Blood and Cerebrospinal Fluid of Patients with Tick-Borne Encephalitis.

BACKGROUND: The detection rate of viral RNA in tick-borne encephalitis (TBE) is low and variable between studies, and its diagnostic/prognostic potential is not well defined. We attempted to detect RNA of TBE virus (TBEV) in body fluids of TBE patients. METHODS: We studied 98 adults and 12 children with TBEV infection, stratified by the disease phase and presentation. EDTA blood and cerebrospinal fluid (CSF) samples were obtained upon hospital admission. RNA was extracted from freshly obtained plasma, concentrated leukocyte-enriched CSF, and whole blood samples, and real time PCR was performed with a Rotor-Gene Q thermocycler. RESULTS: TBEV RNA was detected in (1) plasma of one (of the two studied) adult patients with an abortive infection, (2) plasma of two (of the two studied) adults in the peripheral phase of TBE, and (3) plasma and blood of an adult in the neurologic phase of TBE presenting as meningoencephalomyelitis. No CSF samples were TBEV RNA-positive. CONCLUSIONS: The detection of TBEV RNA in blood might be diagnostic in the peripheral phase of TBE. The lack of TBEV RNA in the CSF cellular fraction speaks against TBEV influx into the central nervous system with infiltrating leukocytes and is consistent with a relatively low intrathecal viral burden.

Expression of the Selected Proteins of JAK/STAT Signaling Pathway in Diseases with Oral Mucosa Involvement.

The JAK/STAT signal pathway is a system of intracellular proteins used by many cytokines and growth factors to express genes responsible for the process of cell activation, proliferation and differentiation. There has been numerous inflammatory and autoimmune diseases identified where the JAK/STAT signaling is disrupted; however, there are only a few papers concerning autoimmune bullous diseases published. The aim of this study was to evaluate the expression of proteins: JAK3, STAT2, STAT4 and STAT6 in epithelium lesions in patients with pemphigus vulgaris (PV), bullous pemphigoid (BP), oral lichen planus (LP) and chronic ulcerative stomatitis (CUS), as well as in the control group. Immunohistochemistry and immunoblotting were used to evaluate expression of selected proteins. We found significantly higher expression of selected JAK/STAT proteins in oral mucosa lesions in study groups in comparison to the control group, which indicates participation of JAK/STAT pathway in pathogenesis of these diseases. In BP and PV there were no increased STAT2 expression, whereas in CUS and LP no increased STAT4 expression occurred. The differences in expression of JAK/STAT proteins in selected disorders have been observed. These results create new potential therapeutic targets for the treatment.

Maintaining plasma quality and safety in the state of ongoing epidemic - The role of pathogen reduction.

In the field of transfusion medicine, many pathogen reduction techniques (PRTs) are currently available, including those based on photochemical (PI) and photodynamic inactivation (PDI). This is particularly important in the face of emerging viral pathogens that may pose a threat to blood recipients, as in the case of the COVID-19 pandemic. However, PRTs have some limitations, primarily related to their adverse effects on coagulation factors, which should be considered before their intended use. A comprehensive search of PubMed, Wiley Online Library and Science Direct databases was conducted to identify original papers. As a result, ten studies evaluating fresh plasma and frozen-thawed plasma treated with different PI/ PDI methods and evaluating concentrations of coagulation factors and natural anticoagulants both before and after photochemical treatment were included in the review. The use of PI and PDI is associated with a significant decrease in the activity of all analysed coagulation factors, while the recovery of natural anticoagulants remains at a satisfactory level, variable for individual inactivation methods. In addition, the published evidence reviewed above does not unequivocally favour the implementation of PI/PDI either before freezing or after thawing as plasma products obtained with these two approaches seem to satisfy the existing quality criteria. Based on current evidence, if implemented responsibly and in accordance with the current guidelines, both PI and PDI can ensure satisfactory plasma quality and improve its safety.

No increase in anti-A isohemagglutinin titer after SARS-CoV-2 infection: A retrospective cohort analysis of group O apheresis platelet donors.

The risk of a hemolytic reaction during the transfusion of ABO non-identical PC is determined by the presence of natural anti-A IgM antibodies, the titer of which may increase after infections. The aim of the study was to evaluate the titer of anti-A isohemagglutinins in platelet concentrate (PC) obtained by apheresis from group O donors who experienced SARS-CoV-2 infection, and to compare the titer before and after infection. A retrospective single-center analysis of 21 PC donors with a previous COVID-19 history was performed. The results showed neither a statistically important increase in the anti-A IgM antibody titers nor a significant correlation between the anti-A IgM antibody level and anti-SARS-CoV-2S1 antibody titer in the donors with an asymptomatic or mild COVID-19. Further population-based studies on anti-A titers are necessary for a comprehensive assessment of this phenomenon.

Utility of Platelet Endothelial Cell Adhesion Molecule 1 in the Platelet Activity Assessment in Mouse and Human Blood.

In our previous study, we introduced the platelet endothelial cell adhesion molecule 1 (PECAM-1)/thrombus ratio, which is a parameter indicating the proportion of PECAM-1 in laser-induced thrombi in mice. Because PECAM-1 is an antithrombotic molecule, the higher the PECAM-1/thrombus ratio, the less activated the platelets. In this study, we used an extracorporeal model of thrombosis (flow chamber model) to verify its usefulness in the assessment of the PECAM-1/thrombus ratio in animal and human studies. Using the lipopolysaccharide (LPS)-induced inflammation model, we also evaluated whether the PECAM-1/thrombus ratio determined in the flow chamber (without endothelium) differed from that calculated in laser-induced thrombosis (with endothelium). We observed that acetylsalicylic acid (ASA) decreased the area of the thrombus while increasing the PECAM-1/thrombus ratio in healthy mice and humans in a dose-dependent manner. In LPS-treated mice, the PECAM-1/thrombus ratio decreased as the dose of ASA increased in both thrombosis models, but the direction of change in the thrombus area was inconsistent. Our study demonstrates that the PECAM-1/thrombus ratio can more accurately describe the platelet activation status than commonly used parameters such as the thrombus area, and, hence, it can be used in both human and animal studies.

Expression of AraC/XylS stress response regulators in two distinct carbapenem-resistant Enterobacter cloacae ST89 biotypes.

BACKGROUND: The growing incidence of MDR Gram-negative bacteria is a rapidly emerging challenge in modern medicine. OBJECTIVES: We sought to establish the role of intrinsic drug-resistance regulators in combination with specific genetic mutations in 11 Enterobacter cloacae isolates obtained from a single patient within a 7 week period. METHODS: The molecular characterization of eight carbapenem-resistant and three carbapenem-susceptible E. cloacae ST89 isolates included expression-level analysis and WGS. Quantitative PCR included: (i) chromosomal cephalosporinase gene (ampC); (ii) membrane permeability factor genes, e.g. ompF, ompC, acrA, acrB and tolC; and (iii) intrinsic regulatory genes, e.g. ramA, ampR, rob, marA and soxS, which confer reductions in antibiotic susceptibility. RESULTS: In this study we describe the influence of the alterations in membrane permeability (ompF and ompC levels), intrinsic regulatory genes (ramA, marA, soxS) and intrinsic chromosomal cephalosporinase AmpC on reductions in carbapenem susceptibility of E. cloacae clinical isolates. Interestingly, only the first isolate possessed the acquired VIM-4 carbapenemase, which has been lost in subsequent isolates. The remaining XDR E. cloacae ST89 isolates presented complex carbapenem-resistance pathways, which included perturbations in permeability of bacterial membranes mediated by overexpression of ramA, encoding an AraC/XylS global regulator. Moreover, susceptible isolates differed significantly from other isolates in terms of marA down-regulation and soxS up-regulation. CONCLUSIONS: Molecular mechanisms of resistance among carbapenem-resistant E. cloacae included production of acquired VIM-4 carbapenemase, significant alterations in membrane permeability due to increased expression of ramA, encoding an AraC/XylS global regulator, and the overproduction of chromosomal AmpC cephalosporinase.

Analysis of CCL-4, CCL-17, CCL-20 and IL-8 concentrations in the serum of patients with tick-borne encephalitis and anaplasmosis.

PURPOSE: Tick-borne co-infections are a serious epidemiological and clinical problem. Only a few studies aimed to investigate the effect of tick-borne encephalitis (TBE) and human granulocytic anaplasmosis (HGA) co-infection in the course of the inflammatory process and the participation of chemokines in the pathomechanism of these diseases. The aim of the study was to evaluate CCL-4, CCL-17, CCL-20, and IL-8 serum concentrations in patients with HGA, TBE and HGA + TBE co-infection. METHODS: Eighty-seven patients with HGA (n = 20), TBE (n = 49) and HGA + TBE (n = 18) were included to the study. The control group (CG) consisted of 20 healthy people. Concentrations of cytokines were measured in serum using commercial ELISA assays. In patients with TBE and HGA + TBE inflammatory markers were assessed during the acute and convalescent period. The results were analyzed using non-parametric tests with p < 0.05 considered as significant. RESULTS: Before treatment, significantly higher concentrations of IL-8, CCL-4 and CCL-20 were observed in HGA patients. CCL-4 and CCL-20 concentrations were significantly higher in TBE patients compared to CG. Concentrations of IL-8, CCL-4, and CCL-20 were significantly higher in HGA + TBE than in CG. After treatment, a significant reduction of IL-8, CCL-4, and CCL-20 concentrations in TBE patients and IL-8 in HGA + TBE co-infection was observed. CCL-4 concentration was higher in HGA + TBE co-infection in comparison to patients with TBE after treatment. CONCLUSIONS: Our study confirms that concentrations of IL-8, CCL-4, and CCL-20 are increased in the course of HGA and TBE. Their concentrations in serum may be used to monitor the course of TBE and HGA, as well as possibly detect co-infections with the diseases.

Assessment of Coxiella burnetii presence after tick bite in north-eastern Poland.

PURPOSE: The aim of the study is to assess anti-Coxiella burnetii antibodies presence in inhabitants of north-eastern Poland, to assess the risk of Q fever after tick bite and to assess the percentage of co-infection with other pathogens. METHODS: The serological study included 164 foresters and farmers with a history of tick bite. The molecular study included 540 patients, hospitalized because of various symptoms after tick bite. The control group consisted of 20 honorary blood donors. Anti-Coxiella burnetii antibodies titers were determined by Coxiella burnetii (Q fever) Phase 1 IgG ELISA (DRG International Inc. USA). PCR was performed to detect DNA of C. burnetii, Borrelia burgdorferi and Anaplasma phagocytophilum. RESULTS: Anti-C. burnetii IgG was detected in six foresters (7.3%). All foresters with the anti-C. burnetii IgG presence were positive toward anti-B. burgdorferi IgG and anti-TBE (tick-borne encephalitis). Anti-C. burnetii IgG was detected in five farmers (6%). Four farmers with anti-C. burnetii IgG presence were positive toward anti-B. burgdorferi IgG and two with anti-TBE. Among them one was co-infected with B. burgdorferi and TBEV. Correlations between anti-C. burnetii IgG and anti-B. burgdorferi IgG presence and between anti-C. burnetii IgG presence and symptoms of Lyme disease were observed. C. burnetii DNA was not detected in any of the 540 (0%) patients. CONCLUSIONS: C. burnetii is rarely transmitted by ticks, but we proved that it is present in the environment, so it may be a danger to humans. The most common co-occurrence after tick bite concerns C. burnetii and B. burgdorferi.

Correlation between IL36α and IL17 and Activity of the Disease in Selected Autoimmune Blistering Diseases.

Dermatitis herpetiformis (DH), bullous pemphigoid (BP), and pemphigus vulgaris (PV) are autoimmune bullous skin conditions with eosinophilic and neutrophilic infiltrations. While cytokines are crucial for the affinity and activation of different leukocyte cells in the inflammation and blister formation, there are no studies concerning a role of IL-36. The goal of the study was to analyze whether interleukin 36 is involved in pathogenesis of DH, BP, and PV. And the second aim of the study was the estimation of correlation between Il-36 and IL-17 and titers of specific antibodies in these diseases. Expression of IL-36 and IL-17 was detected in serum in all DH, BP, and PV samples. Serum levels of IL-36 and IL-17α were statistically higher in DH, BP, and PV groups as compared to the control group. IL-36α levels were statistically higher in DH patients, as compared to patients with PV and BP. Our results showed that IL-36 may be helpful in the diagnostic and monitoring of the activity of the disease. IL 36 may play a relevant role of enrolling eosinophils and neutrophils in DH, BP, and PV and finally provoke tissue injury.

ABCB1 gene is associated with the risk of bullous pemphigoid in a polish population.

BACKGROUND AND OBJECTIVES: Polymorphisms in the P-glycoprotein-encoding ABCB1 gene may affect the intracellular concentration of xenobiotics, and thus contribute to the development of autoimmune diseases, including bullous pemphigoid (BP). The objective of the present study was to investigate whether there is an association between the C3435T and G2677T/A polymorphisms in the ABCB1 gene and the risk of BP in a Polish population. PATIENTS AND METHODS: The study included 71 patients with BP and 156 healthy volunteers. Determination of the C3435T polymorphism was carried out using PCR-RFLP; the G2677T/A polymorphism, using allele-specific PCR. RESULTS: While there was no correlation between the C3435T polymorphism and the risk of BP, we did find such an association with respect to the G2677T/A polymorphism. The relative risk of BP was more than five times greater in individuals with the 2677TA genotype (OR = 5.52, p = 0.0063), and more than twice as high in carriers of the 2677TT genotype (OR = 2.40, p = 0.0076). At 2.40 (0.000018), the OR in carriers of the 2677T allele was also increased. The greater prevalence of the 2677GG genotype and the 2677G allele in the control group, as well as the OR < 1.0 (0.22 and 0.33, respectively), suggest a protective role of the 2677G allele with respect to the development of BP. CONCLUSIONS: The results of the present study indicate that the G2677T/A polymorphism in the ABCB1 gene may affect the risk of developing BP.

ABCB1-Gen-Polymorphismus in einer polnischen Kohorte ist mit Risiko für bullöses Pemphigoid assoziiert.

HINTERGRUND UND ZIELE: Polymorphismen im ABCB1-Gen, das für das P-Glykoprotein kodiert, können die intrazelluläre Konzentration von Xenobiotika beeinflussen und so zur Entwicklung von Autoimmunerkrankungen, einschließlich des bullösen Pemphigoids (BP), beitragen. In der vorliegenden Studie sollte untersucht werden, ob in einer polnischen Kohorte die C3435T- und G2677T/A-Polymorphismen im ABCB1-Gen mit dem Risiko für ein BP assoziiert sind. PATIENTEN UND METHODIK: Die Studie umfasste 71 Patienten mit BP und 156 gesunde Probanden. Der C3435T-Polymorphismus wurde mittels PCR-RFLP bestimmt und der G2677T/A-Polymorphismus mittels Allel-spezifischer PCR. ERGEBNISSE: Es gab zwar keine Korrelation zwischen dem C3435-Polymorphismus und dem BP-Risiko, aber wir konnten eine derartige Assoziation hinsichtlich des G2677T/A-Polymorphismus nachweisen. Das relative Risiko eines BP war bei Personen mit dem 2677TA-Genotyp um mehr als den Faktor fünf erhöht (OR = 5,52; p = 0,0063) und bei Trägern des 2677TT-Genotyps mehr als verdoppelt (OR = 2,40; p = 0,0076). Mit 2,40 (p = 0,000018) war die OR bei Trägern des 2677T-Allels ebenfalls erhöht. Die höhere Prävalenz des 2677GG-Genotyps und des 2677G-Allels bei der Kontrollgruppe sowie eine OR < 1,0 (0,22 beziehungsweise 0,33) legen eine Schutzfunktion des 2677G-Allels hinsichtlich der Ausbildung eines BP nahe. SCHLUSSFOLGERUNGEN: Die Ergebnisse der vorliegenden Studie zeigen, dass der G2677T/A-Polymorphismus im ABCB1-Gen das Risiko für die Entstehung eines BP beeinflussen könnte.

Tissue Factor in Dermatitis Herpetiformis and Bullous Pemphigoid: Link between Immune and Coagulation System in Subepidermal Autoimmune Bullous Diseases.

Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although chemokines are critical for the selective accumulation and activation of various leukocyte subsets in the inflammatory process, there are few findings concerning inflammatory cells and production of coagulation factors in blistering diseases. Skin biopsies were taken from 14 patients with DH, 27 with BP, and 20 control subjects. The localization and expression of tissue factor (TF) in skin lesions and perilesional skin were studied by immunohistochemistry and confirmed by Western Blot. Moreover the plasma concentrations of TF were measured by immunoassays. D dimers, fibrinogen, and selected coagulation parameters were measured by routine methods. Expression of TF in the epidermis and in inflammatory influxed cells in dermis was detected in skin biopsies from BP patients. Examined TF expression was detected in perilesional skin of all BP patients too. The expression of TF was not observed in biopsies from healthy people and DH patients. The findings of the study show an increased expression of tissue factor in the lesional and perilesional skin of patients with bullous pemphigoid. The difference in chemokine pattern expression and variations in the cellular infiltration in BP and DH cause variable expression of TF.

Mediators of mast cells in bullous pemphigoid and dermatitis herpetiformis.

Bullous pemphigoid (BP) and dermatitis herpetiformis (DH) are skin diseases associated with inflammation. However, few findings exist concerning the role of mast cells in autoimmune blistering disease. Skin biopsies were taken from 27 BP and 14 DH patients, as well as 20 healthy individuals. Immunohistochemistry was used to identify the localization and mast cell expression of TNFα and MMP9 in skin lesions and perilesional skin. The serum concentrations of TNFα, MMP9, chymase, tryptase, PAF, and IL-4 were measured by immunoassay. TNFα and MMP9 expression in the epidermis and in inflammatory influxed cells in the dermis was detected in skin biopsies from patients. Although these mediators were found to be expressed in the perilesional skin of all patients, the level was much lower than that in lesional skin. Increased serum PAF levels were observed in BP patients. Mast cells may play an essential role in activating inflammation, which ultimately contributes to the tissue damage observed in BP and DH. Our findings suggest that differences in the pattern of cytokine expression directly contribute to variations in cellular infiltration in DH and BP.

The Spectrum of Cutaneous Manifestations in Lupus Erythematosus: A Comprehensive Review.

Lupus erythematosus (LE) is an autoimmune inflammatory disease with complex etiology. LE may present as a systemic disorder affecting multiple organs or be limited solely to the skin. Cutaneous LE (CLE) manifests with a wide range of skin lesions divided into acute, subacute and chronic subtypes. Despite classic forms of CLE, such as malar rash or discoid LE, little-known variants may occur, for instance hypertrophic LE, chilblain LE and lupus panniculitis. There are also numerous non-specific manifestations including vascular abnormalities, alopecia, pigmentation and nail abnormalities or rheumatoid nodules. Particular cutaneous manifestations correlate with disease activity and thus have great diagnostic value. However, diversity of the clinical picture and resemblance to certain entities delay making an accurate diagnosis The aim of this review is to discuss the variety of cutaneous manifestations and indicate the clinical features of particular CLE types which facilitate differential diagnosis with other dermatoses. Although in diagnostically difficult cases histopathological examination plays a key role in the differential diagnosis of LE, quick and accurate diagnosis ensures adequate therapy implementation and high quality of life for patients. Cooperation between physicians of various specialties is therefore crucial in the management of patients with uncommon and photosensitive skin lesions.

IL-17 expression in dermatitis herpetiformis and bullous pemphigoid.

Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although cytokines are critical for the inflammatory process, there are single findings concerning concentration of IL-17 in bullous diseases. The goal of this study was to assess IL-17 expression in DH and BP patients. Skin biopsies were taken from 10 DH, 14 BP patients and from 10 healthy subjects. The localization and expression of IL-17 was studied by immunohistochemistry and the serum concentration was measured by immunoassays. Expression of IL-17 in the epidermis and in influxed cells in dermis was detected in skin biopsies. Expression of IL-17 was statistically higher in epidermis and infiltration cells in specimens from BP than from DH patients. Examined interleukin expression was detected in perilesional skin of all patients but it was much lower than in lesional skin. The expression of IL-17 was not observed in biopsies from healthy people. Serum level of IL-17 was statistically higher in BP and DH groups as compared to control group. Our results provide the evidence that IL-17 may play an essential role in activating and recruiting eosinophils and neutrophils, which ultimately contribute to the tissue damage in DH and BP.

Genetic polymorphisms of CYP2D6 oxidation in patients with autoimmune bullous diseases.

INTRODUCTION: Bullous skin diseases, which include, among others pemphigoid, pemphigus, and dermatitis herpetiformis are classified as severe autoimmune dermatoses. It has been shown that a pattern of xenobiotic metabolism may play a role in the pathogenesis of autoimmune diseases. AIM: To estimate whether the CYP2D6 genotype may be considered a predisposing factor in autoimmune bullous diseases induction. MATERIAL AND METHODS: The study included 72 patients with autoimmune bullous diseases: 37 with pemphigoid, 21 with pemphigus, and 14 with dermatitis herpetiformis (DH). The CYP2D6 genotypes were analyzed by the polymerase chain reaction fragment length polymorphism (PCR-RFLP) method. RESULTS: Relative risk of DH development for particular genotype carriers expressed by odds ratio (OR) was statistically significantly higher for subjects with CYP2D6*1/CYP2D6*4 (OR = 4.2; p = 0.0104) and 2-fold higher for subjects with CYP2D6*4 (OR = 2.3; p = 0.0351). CONCLUSIONS: The results of the present study show that the CYP2D6 oxidation polymorphism cannot be considered a risk factor for development of pemphigoid and pemphigus, however it might have an impact on dermatitis herpetiformis.