Introduction:Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening mucocutaneous reactions with high mortality. The A severity-of-illness score for toxic epidermal necrolysis (SCORTEN) scale remains the principal tool for early estimation of in-hospital death risk. The study was aimed to assess the predictive value of individual SCORTEN components for hospital mortality in a real-world Moscow cohort and to characterize demographic and etiologic factors associated with outcome. Methods:We retrospectively reviewed 150 adult patients (median age 50 years; IQR: 31-63; 59.3% female) admitted with SJS (45.3%) or TEN (54.7%) between 2019 and 2024. SCORTEN parameters were recorded within 24 h of admission. Univariate analyses (chi-square or Fisher's exact test) identified associations between each SCORTEN variable and in-hospital death. Kaplan-Meier survival curves and Cox proportional-hazards models quantified time-to-event outcomes and adjusted hazard ratios (HR). Results:Overall mortality was 18.7% (n = 28). In univariate analysis, age >40 years (OR: 3.53; p = 0.01), associated malignancy (OR: 3.35; p = 0.03), heart rate > 120 bpm (OR: 9.42; p < 0.001), serum urea >28 mg/dL (OR: 14.25; p < 0.001), and bicarbonate <20 mmol/L (OR: 7.25; p < 0.001) were significantly linked to death. In multivariate Cox regression, malignancy (HR: 3.57; p = 0.05), urea > 28 mg/dL (HR: 4.33; p = 0.03), and tachycardia (HR: 2.77; p = 0.04) remained independent predictors. Initial epidermal detachment, serum glucose, and age did not retain significance. Discussion:These findings support continued use of SCORTEN while highlighting the need to recalibrate or augment its parameters-particularly renal and oncologic variables-to improve risk stratification in current therapeutic contexts.

Renal cell carcinoma (RCC) is a prevalent and heterogeneous malignancy with clear cell RCC (ccRCC) as the most common subtype. Despite advances in surgical, targeted, and immunotherapeutic approaches, prognosis for advanced and metastatic RCC remains poor, and the effectiveness of current immunotherapies is limited by immune tolerance, tumor heterogeneity, and adverse effects. The identification of tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs) is crucial for the development of personalized and effective antigen-directed therapies, including vaccines, antibodies and adoptive cell therapies. This review summarizes epidemiological data, molecular features of RCC, and the role of the von Hippel Lindau – Hypoxia Inducible Factor (VHL-HIF) signaling pathway in pathogenesis, alongside recent progress in characterizing possible antigen targets for vaccination such as TOP2A, NCF4, FMNL1, DOK3, MUC1, CAIX, CD70, and 5T4. Preclinical models, including genetically engineered mouse models, zebrafish, and various patient-derived xenograft (PDX) systems, are discussed as tools for studying tumor biology and testing immunotherapeutic strategies. Clinical trial data on RCC vaccines, including autologous renal tumor cell vaccination, peptide-based, dendritic cell-based, and viral vector platforms, demonstrate immunogenicity but have not yet yielded clear survival benefits in phase III trials. Future directions emphasize integrating antigen discovery with immune profiling, refining preclinical modeling, and developing personalized vaccines to enhance therapeutic efficacy, particularly for immunologically favorable patient subtypes and for certain applications such as reducing metastasis after surgery. In particular, we discuss carrier-based vaccine approaches for overcoming tolerance and increasing the immunogenicity of vaccines.

Background/Objectives: This study aims to fill certain knowledge gaps by assessing the clinical effectiveness of PDT in a large group of women with HPV-related cervical lesions and examining how different patient factors affect treatment results. Methods: A total of 811 women aged from 19 to 76 were retrospectively analyzed who were treated by PDT of HPV infection with atypical squamous cells and HPV-related cervical lesions. PDT was performed using chlorin e6-based systemic photosensitizers. Irradiation was carried out at 662 nm. The endocervical dose was 334 J/cm(2), and the ectocervical dose was 291 J/cm(2). Results: Overall HPV clearance was 91.1%, lesion remission was 95.3%, and complete response was 88.3%, with the highest complete response observed in the HSIL group compared with HPV-positive ASCs. Multivariable models showed that multiple HPV infection (especially >3 genotypes) and pregnancy history were associated with lower odds of complete response, while younger age (18-25 years) and TZ2 were associated with higher odds of complete response. Conclusions: PDT using chlorin e6-based photosensitizers demonstrated high clinical and virological effectiveness across HPV-related cervical abnormalities, including HSIL, supporting its role as an organ-preserving treatment option. Multiple HPV genotypes and pregnancy history may identify patients at increased risk of partial response and warrant closer follow-up or tailored treatment strategies.

Allergy is the most common hypersensitivity disorder, affecting around 30% of the global population. Due to its rapidly increasing prevalence and significant reduction in quality of life for patients, allergy represents a major public health problem, and the improvement of diagnostic and treatment options for allergic diseases is of utmost importance. Moreover, the development of preventive allergen-specific immunization strategies is an emerging research direction in mitigating allergy incidence, especially for respiratory diseases such as allergic rhinitis and asthma. Since environmental allergen exposures differ substantially depending on climatogeographical, ecological, and behavioral factors, investigating local IgE sensitization profiles could significantly contribute to optimizing allergy management. We performed a systematic database review to summarize available knowledge on IgE sensitization profiles in Russia across different regions of the country. The study was conducted in compliance with PRISMA and SWiM guidelines and registered in the PROSPERO database (CRD420250650847). We identified major differences in sensitization profiles across certain geographical areas, reported in 60 studies. However, heterogeneity of methods and gaps in the existing evidence were noted, and, as the available data appear insufficient for reliable profiling, an outline was proposed for systematic and methodologically harmonized studies necessary to develop further region-tailored approaches.

Engineered nano- and microparticles are considered as promising tools in biomedical applications, such as imaging, sensing, and drug delivery. Protein adsorption on these particles in biological media is an important factor affecting their properties, cellular interactions, and biological fate. Understanding the parameters determining the efficiency and pattern of protein adsorption is crucial for the development of effective biocompatible particle-based applications. This review focuses on the influence of the morphological and physicochemical properties of particles on protein adsorption, including the pattern and amount of the adsorbed protein species, as well as the relative abundance of proteins with specific functions or physicochemical parameters. The effects of functionalization of the particle surface with polyethylene glycol, zwitterions, zwitterionic polymers, or proteins on the subsequent protein adsorption are analyzed. In addition, the dependences of protein adsorption on the protein species, biological buffers, fluids, tissues, and other experimental conditions are looked into. The influence of protein adsorption on the targeting efficiency of particle-based delivery systems is also discussed. Finally, the effect of the adsorbed protein corona on the interaction of the engineered micro- and nanoparticles with cells and the roles of specific proteins adsorbed on the particle surface in the recognition of the particles by the immune system are considered.

Background:Chronic inducible urticaria (CIndU) is characterized by wheals and/or angioedema (AE) for 6 weeks or more in response to specific and definite triggers. Individual patients can have more than one type of CIndU. Reports on this come from single cases or small case series, most epidemiological studies did not assess whether these urticaria are standalone or mixed. Objective:Determine the features of mixed CIndU and how they differ from standalone forms. Methods:In a prospective cohort study we performed provocative testing in 210 patients with CIndU. A total of 188 patients were included (125 with the standalone CIndU and 63 with the mixed CIndU. Within each group, patients were divided into subgroups: symptomatic dermographism (SD), cold (ColdU) and cholinergic urticaria (CholU). Results:Mixed CIndU most commonly were SD+ColdU (n=19, 30.2%), SD+CholU (n=15, 23.8%), SD+DPU (n=12, 19%) and ColdU+CholU (n=9, 14.3%). Comorbid chronic spontaneous urticaria (CSU) (50.8% vs 20.8, p<0.001) and AE (36.5% vs. 20%, p=0.014) were more common in patients with mixed CIndUs. In patients with mixed CIndUs, their onset time is more closely linked to each other (n=43; 68.2%) as compared to that of comorbid CSU (12 of 32, 37.5%). MixedSD patients are younger, show earlier onset of disease and have higher rates of AE and lower rates of atopic dermatitis (AtD), as compared to patients with standalone SD. MixedColdU patients have higher rates of comorbid CSU and lower rates of AtD, higher levels of total IgE and eosinophils. MixedCholU patients are older, have a high rate of comorbid CSU, a lower incidence of allergic disease. Conclusion:This study shows for the first time that each combinations of mixed CIndU represent a distinct phenotype with its own features. These phenotypes require special attention of specialists.

Background Allergic sensitization to cats and other furry animals is a major cause of asthma and allergic rhinitis in more than 200 million people worldwide. According to the frequency of IgE recognition, allergen-specific IgE levels, and allergenic activity, Fel d 4 is a major allergen in the cat (Felis domesticus). The lipocalin allergen Fel d 4 is highly homologous to dog (Can f 6) and major horse (Equ c 1) allergens. Accordingly, IgE cross-reactivity to these allergens contributes to polysensitization and allergic responses upon exposure to different animals.Methods Fel d 4 was recombinantly produced in two systems, E. coli and Expi293F mammalian cells. Recombinant forms were characterized by circular dichroism and mass spectrometry. The Fel d 4 3D structure was determined using X-ray crystallography. Immunoreactivity, epitope analyses, and cross-reactive properties were assessed by ELISA and basophil release assays using allergic patients' sera.Results We reveal the rFel d 4 crystal structures and demonstrate that mammalian cells produce an N-glycosylated recombinant Fel d 4 allergen. The C-terminal regions of Fel d 4, Can f 6, and Equ c 1 constitute conformational IgE-epitope-containing areas responsible for cross-reactivity.Conclusion Uncovering the IgE-binding sites of Fel d 4 and cross-reactive allergens contributes to future rational design of active and passive allergen-specific treatment forms.

Significance The first obstacle to human papillomavirus (HPV) is Toll-like receptors (TLRs). Research has revealed that TLR signaling demonstrating both tumor-suppressive and tumor-promoting effects Approach 2-ddCt value of m RNA TLR2, 3, 4 and 8 expressions after PDT in 121 women with HPV-related cervical lesions. Results TLR8 showed the most consistent reduction across all groups with the strongest suppression in cervical cancer cases. Conclusions TLR8 has the potential to serve as a novel earlier molecular immunological marker for the progression of HPV infection. TLR4 may represent an additional marker due to its reduced expression after PDT in cervical cancer.

Photodynamic therapy (PDT) is a minimally invasive treatment with low systemic toxicity and immunomodulatory effects, increasingly applied in managing HPV-associated cervical lesions. Toll-like receptors (TLRs) are critical in regulating immune responses in cervical pathology, yet their dynamics under PDT remain underexplored. This study investigates the effect of PDT on TLR2, TLR3, TLR4, and TLR8 expression in cervical epithelial cells ex vivo, considering lesion severity. The results reveal that TLR8 exhibited the most significant reduction across all groups 2 h after PDT, with the strongest suppression in patients with invasive cervical cancer. TLR4 expression decreased by 24% in HPV-infected patients and by 71% in those with cervical cancer, highlighting its potential role in modulating the inflammatory microenvironment post-PDT. TLR3 showed hyperexpression in LSIL and suppression in HSIL/CIN III, although changes were not statistically significant (p > 0.05). TLR2 expression remained unchanged, likely due to HPV type variability. These findings demonstrate that PDT effectively reduces hyperexpression of TLR8, TLR4, and TLR3 in early-stage cervical cancer, suggesting their potential as biomarkers for treatment efficacy. Further research incorporating HPV typing and advanced techniques like liquid biopsy is essential to refine our understanding of TLRs in PDT for HPV-associated cervical lesions.

BACKGROUND:Molecular forms of allergen-specific immunotherapy (AIT) for cat allergy are needed. Fel d 1, Fel d 4, and Fel d 7 are the most important cat allergens. METHODS:IgE epitopes of Fel d 4 and Fel d 7 were mapped by blocking allergic patients' IgE binding with allergen peptide-specific antisera. Five recombinant fusion proteins (PreS-Cat 1-PreS-Cat 5) each containing hepatitis B virus (HBV)-derived PreS as an immunological carrier and non-allergenic peptides from the IgE binding sites of Fel d 1, Fel d 4, and Fel d 7 were expressed in Escherichia coli, purified, and characterized by mass spectrometry, circular dichroism (CD), and size exclusion chromatography. ImmunoCAP and basophil activation experiments demonstrated the hypoallergenic activity of PreS-Cat 1-5. The ability of PreS-Cat 1-5 to induce IgE-blocking antibodies in rabbits was compared to three licensed allergen extract-based AIT vaccines. PreS-Cat 1-5-specific IgG antibodies were tested for inhibition of allergen-specific IgE binding and specific basophil activation. T cell activation and induction of specific cytokine secretion by PreS-Cat proteins were compared with cat allergens in PBMC cultures. RESULTS:Recombinant hypoallergenic, biochemically and structurally defined PreS-Cat 1-5 were obtained. Two subcutaneous immunizations of rabbits with PreS-Cat 1-5 induced equal (Fel d 1) or better (Fel d 4 and Fel d 7) antibodies (PreS-Cat 5 > PreS-Cat 1 > PreS-Cat 3) blocking allergic patients' IgE binding to cat allergens than six to fifteen immunizations with allergen extract-based vaccines. PreS-Cat-specific antibodies strongly inhibited specific basophil activation. PreS-Cat 5 > PreS-Cat 1 induced significantly more IL-10 in cultured PBMCs from cat allergic patients than cat allergens. CONCLUSIONS:PreS-Cat 5 and PreS-Cat 1 are highly promising molecular vaccine candidates for AIT of cat allergy, combining Fel d 1-, Fel d 4-, and Fel d 7-peptides in single PreS fusion proteins.

In this article we discuss characteristics of fusion protein-based SARS-CoV-2 vaccines. We focus on recombinant vaccine antigens comprising fusion proteins consisting of combinations of SARS-CoV-2-derived antigens or peptides or combinations of SARS-CoV-2 antigens/peptides with SARS-CoV-2-unrelated proteins/peptides. These fusion proteins are made to increase the immunogenicity of the vaccine antigens and/or to enable special targeting of the immune system. The protein-based vaccine approach is exemplified solely in a proof of concept study by using W-PreS-O, a chimeric vaccine based on a single fusion protein (W-PreS-O), combining RBDs from Wuhan hu-1 wild-type and Omicron BA.1 with the hepatitis B virus (HBV)-derived PreS surface antigen adsorbed to aluminum hydroxide. The W-PreS-O vaccine was evaluated in Syrian hamsters which were immunized three times at three-week intervals with W-PreS-O or with aluminum hydroxide (placebo) before they were infected with Omicron BA.1. Neutralizing antibody (nAB) titers, weight, lung symptoms, and viral loads, as measured using RT-PCR in the upper and lower respiratory tracts, were determined. In addition, infectious virus titers from the lungs were measured using a plaque-forming assay. We found that W-PreS-O-vaccinated hamsters developed robust nABs against Omicron BA.1, showed almost no development of pneumonia, and had significantly reduced infectious virus titers in the lungs. Importantly, the viral loads in the nasal cavities of W-PreS-O-vaccinated hamsters were close to or above the PCR cycle threshold considered to be non-infectious. The data of our proof-of-concept study provides compelling evidence that the W-PreS-O vaccine has protective effect against Omicron BA.1 in a Syrian hamster in vivo infection model and thus support the promising results obtained also for other fusion protein-based SARS-CoV-2 vaccines.

Background: Chronic hepatitis B (CHB) remains being a major public health threat, and currently existing CHB therapies have limited efficacy and side effects. We have recently developed a vaccine termed VVX001 based on a recombinant fusion protein consisting of the preS domain of the large surface protein of hepatitis B virus (HBV) fused to grass pollen allergen peptides. VVX001 has been shown to induce preS-specific antibodies in grass pollen allergic patients, and sera of immunized subjects inhibited HBV infection in vitro. Methods: In this study we investigated if immunization with VVX001 can induce preS-specific antibodies in CHB using the adeno-associated virus (AAV)-HBV murine model of CHB. Six groups of C57BL/6 female mice (n = 6) were transduced with AAV-HBV or AAV-Empty, and after six weeks, they were immunized five times with 20 µg of aluminum hydroxide-adsorbed VVX001 or preS or vehicle (Alum alone). Serum samples were taken continuously. Two weeks after the last immunization, spleen and liver mononuclear cells were collected. Serum reactivity to preS and preS-derived peptides was assessed by ELISA. B-cell responses were measured by ELISPOT assay, and intrahepatic lymphocyte (ILH) counts were determined by FACS. HBV DNA, HBsAg, HBeAg, ALT, and AST were assessed using commercial kits. Results: Our results show that VVX001 induces preS-specific IgG antibodies that cross-react with different HBV genotypes A-H and are directed against the sodium taurocholate co-transporting polypeptide (NTCP) receptor binding site of preS both in mice with and without HBV. Actively immunized AAV-HBV-treated mice had a higher number of intrahepatic lymphocytes than vehicle-vaccinated and mock-transduced animals. Conclusions: These findings encourage performing further trials to study the potential of VVX001 for therapeutic vaccination against CHB.

A heterozygous mutation in the PTPN2 gene has recently been described in several patients exhibiting symptoms of immune dysregulation. The gene encodes a ubiquitous non-receptor T-cell protein tyrosine phosphatase that exerts a negative feedback on the JAK-STAT pathway. Limited clinical data are available advocating the use of JAK inhibitors as an effective treatment for autoimmune complications of PTPN2 deficiency. However, the mechanism of pathogenesis for these complications suggests this possibility. We report on a 32-year-old male patient with interstitial lung disease, cytopenia, and lymphadenopathy accompanied by de-novo deletion in PTPN2. The patient has been receiving systemic steroid treatment for decades, which has resulted in hormone dependence as well as therapy-related adverse side effects. After the diagnosis of PTPN2 deficiency, treatment with the JAK inhibitor ruxolitinib was initiated at a dose of 15 mg per day, which was escalated to 30 mg daily after 1 month. The steroid treatment was discontinued within 3 months. At the 9- and 16-month checkpoint, after 6 and 13 months correspondingly of monotherapy with ruxolitinib at a dosage of 30 mg per day, the patient had stable blood counts, lymphadenopathy decreased, and the lung interstitial disease improved. Thus, according to our experience, JAK inhibitors are able to alleviate the PTPN2 deficiency symptoms, including hematological changes and interstitial lung damage.

BACKGROUND:Molecular immunoglobulin E (IgE) reactivity profiling with multiple micro-arrayed allergens is a valuable tool in allergy diagnosis and has provided fundamental insights into the evolution of allergic sensitization in longitudinal birth cohort studies. However, there is a need for systematic cross-sectional population-based studies. METHODS:A prospective, systematic and cross-sectional population study was performed involving 1000 adult subjects from five centers (İstanbul, Ankara, İzmir, Kayseri, Samsun) representing different climatic areas of Türkiye (Turkey). In each center adult subjects with (n = 100) and without (n = 100) allergic symptoms who were born and grew up in the region were recruited. Subjects underwent skin prick testing with a panel of common aeroallergen extracts and were tested for IgE reactivity to 108 micro-arrayed allergen molecules. RESULTS:IgE reactivity profiles of respiratory allergens differed in the five centers according to the regional allergen exposome and climate. Interestingly, Kayseri with a high-altitude, continental climate was identified as hypoallergenic region with low frequency of allergic symptoms and strongly reduced molecular sensitization rates. Between 31%-55% of subjects without allergic symptoms showed IgE sensitization to at least one of the allergens tested but allergen-specific IgE levels, numbers of recognized allergens and rates of poly-sensitization were more frequent in symptomatic individuals. CONCLUSIONS:This is the first comprehensive, systematic, prospective and cross-sectional study investigating molecular IgE sensitization profiles in a region at the crossroads of Europe, Asia, and Africa with different climatic conditions. It reveals clinically relevant differences in regional molecular IgE sensitization profiles depending on the allergen exposome and identifies a hypoallergenic region with distinct climatic features.

The prevalence of allergic diseases has increased tremendously in recent decades, which can be attributed to growing exposure to environmental triggers, changes in dietary habits, comorbidity, and the increased use of medications. In this context, the multiplexed diagnosis of sensitization to various allergens and the monitoring of the effectiveness of treatments for allergic diseases become particularly urgent issues. The detection of allergen-specific antibodies, in particular, sIgE and sIgG, is a modern alternative to skin tests due to the safety and efficiency of this method. The use of allergen microarrays to detect tens to hundreds of allergen-specific antibodies in less than 0.1 mL of blood serum enables the transition to a deeply personalized approach in the diagnosis of these diseases while reducing the invasiveness and increasing the informativeness of analysis. This review discusses the technological approaches underlying the development of allergen microarrays and other protein microarrays, including the methods of selection of the microarray substrates and matrices for protein molecule immobilization, the obtainment of allergens, and the use of different types of optical labels for increasing the sensitivity and specificity of the detection of allergen-specific antibodies.

Chlorine E6 photodynamic therapy (PDT) was used to treat 183 patients with HPV-related cervical diseases. The main of this study was to characterize the local immune response during treatment with PDT in patients with persistent HPV infection, LSIL, HSIL and cervical cancer. PDT is able to stimulate antiviral innate immune response, being important to treatment effectiveness.

Polyelectrolyte microparticles (MPs) synthesized on calcium carbonate cores are considered a promising basis for new drug delivery systems. It is known that microparticles entering a physiological environment absorb proteins on their surface, which can change the properties of the microparticles and alter their functional activity. This study aimed to compare the compositions of the adsorbed protein layer formed on microparticles with the core/shell and shell structures obtained by layer-by-layer deposition. The difference in the microparticle structure was associated with changes in their surface topography and zeta-potential. These microparticles were incubated with human serum or plasma at 37 degrees C for 24 h. The adsorbed proteins were eluted and analyzed by means of SDS-PAGE. The protein composition of the eluates was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS); a total of 357 proteins were identified, and 183 of them were detected in all samples. Our results demonstrate that the relative abundance of proteins of different functional groups (immunoglobulins, complement proteins, and apolipoproteins) varied depending on the structure and surface characteristics of the polyelectrolyte microparticles and the incubation medium. Our findings expand the understanding of the influence of the physicochemical properties of the microparticles on their interaction with proteins, which can help to improve the design of microparticles for drug delivery.

BACKGROUND: Diagnosis and treatment of COVID-19 in patients with primary immunodeficiency, or inborn errors of immunity, are often challenging. AIM: Description of the COVID-19 course and therapy of adult patients with primary immunodeficiency treated in medical organizations of Moscow Healthcare Department. MATERIALS AND METHODS: We analyzed a cohort of 68 patients over 18 years (median ― 35 years) with primary immunodeficiency; 91% of patients have primary immunodeficiency with predominantly antibody deficiencies. Altogether 90 cases of the new СOVID-19 were analyzed: in 68 cases infection occurred for the first time, in 22 cases it recurred. The duration of the disease ranged from 3 to 80 days. Duration of PCR-positivity ranged from 0 to 59 days, median 8 days. RESULTS: Patients with Wuhan and Delta strains had more severe inflammatory signs according to C-reactive protein and lactate dehydrogenase, in patients with Wuhan lung involvement on CT-scam was larger. In demonstrated group of patients higher C-reactive protein correlated with larger lung involvement, longer duration of the disease and PCR-positivity, significant lymphopenia also correlated with higher C-reactive protein. To our data regularity of intravenous immunoglobulin therapy and IgG trough level didn’t correlate with infection severity and duration of the disease and virus-carriage. Indirectly, the change in the spectrum of medicine used in patients of the analyzed group coincided with the virus strain evolution. Anti-inflammatory therapy was mainly presented by dexamethasone and antagonists to interleukin 6 or its receptor (anti-IL-6): 55% and 73% for Wuhan, 63% and 50% for Delta, 17% and 39% for Omicron. Then, preference was gradually given to the target anti-cytokine medicine. Etiotropic antiviral therapy was more often used to treat infection caused by Wuhan and Delta strains ― 32% and 38%, respectively (in 17% for Omicron). With shifting toward immunotherapy by specific against COVID-19 immunoglobulins and monoclonal antibody to SARS-CoV-2: 5% and 9% for Wuhan, 0% and 75% for Delta, 48% and 83% for Omicron, respectively. Immune and etiotropic therapy was not carried out in Wuhan in 39%, in Delta in 43%, in Omicron in 41% of cases. The overall mortality rate from COVID-19 in the analyzed group was 3%. CONCLUSION: Patients with primary immunodeficiency represent a vulnerable group to the SARS-CoV-2 virus with a high risk of not only severe, but also a protracted and undulating course of infection, what must be taken into account for the correct interpretation of the patient's condition and the timely administration of the appropriate therapy.