Our study is the first in Bulgaria in which cluster analysis is applied to asthmatic patients. We identified four clusters. The variables with greatest force for differentiation in our study were: age of asthma onset, duration of diseases, atopy, smoking, blood eosinophils, nonsteroidal anti-inflammatory drugs hypersensitivity, baseline FEV1/FVC and symptoms severity. Our results support the concept of heterogeneity of bronchial asthma and demonstrate that cluster analysis can be an useful tool for phenotyping of disease and personalized approach to the treatment of patients.

Background Oral Squamous Cell Carcinoma (OSCC) is a malignancy characterized by an aggressive tumor growth and significant mortality. Clarifying mechanisms responsible for immunomodulation are among the main challenges for the development of personalized approaches for the management of patients with Oral Squamous Cell Carcinoma. The aim of the present study was to analyze the relevance of MICA and MICB to Oral Squamous Cell Carcinoma pathogenesis focusing on allele polymorphisms and the levels of soluble MICA and MICB molecules. Materials and methods 73 patients diagnosed with Oral Squamous Cell Carcinoma and 149 healthy controls from the Bulgarian population were included in the study. MICA and MICB polymorphism was analyzed at high‐resolution level using Next‐Generation Sequencing. Serum levels of soluble MICA and MICB molecules were measured by ELISA. Results Our results show significant protective association with MICB*002:01, while relatively rare alleles MICB*018, *019, and *020 were observed with statistically significant increased frequency in Oral Squamous Cell Carcinoma patients compared to controls. Additionally, a predisposing association was observed for MICA*008:01‐MICB*019 haplotype. A correlation analysis between functionally relevant MICA polymorphisms and sMICA showed that homozygosity for MICA‐A5.1 or 129Val in OSCC patients was associated with significantly higher serum levels of sMICA. Conclusion This is the first study showing significant associations between MICB alleles and Oral Squamous Cell Carcinoma and suggesting the possible role of MICB in immunosurveillance in Oral Squamous Cell Carcinoma development. Observed correlations between the levels of soluble MICA molecules and functionally relevant polymorphisms might represent a further step toward a better understanding of molecular mechanisms of Oral Squamous Cell Carcinoma and developing strategies for therapeutic targeting harnessing effective immunosurveillance.

Vaccination against the SARS‐Cov‐2 virus is an effective way to protect against the disease and the severe course of COVID‐19. Forty‐nine fully vaccinated with mRNA vaccines (BNT162b2 or mRNA‐1273) SARS‐CoV‐2 infection‐naïve volunteers aged 33–89 were enrolled in the study. Evaluation of the cellular and humoral immune response was performed within 1 to 3 months (T1) and 6–9 months (T2) after the second injection, and within 2–3 months (T3) after a booster dose. Additionally, a comparative analysis of the specific immune status was made between two age groups—below 60 (n = 22) and over 60 (n = 27) years. SARS‐CoV‐2‐specific T‐cell response was evaluated by IFN‐γ‐producing spot forming cells (SFCs) using a standardized ELISPOT assay. Virus neutralizing antibodies (VNA) against SARS‐CoV‐2 were measured by a blocking ELISA test and spike protein specific IgG (S‐IgG) and IgA (S‐IgA) antibodies—by semiquantitative ELISA. IFN‐γ‐producing SFCs, S‐IgG, S‐IgA and VNA significantly decreased 6–9 months after the second dose. After the third injection S‐IgG and S‐IgA markedly increased compared to T2 and reached the levels at T1. Of note, the highest values of VNA were observed at T3. No differences in the tested immune parameters were found between the two age groups. Data obtained showed that for a long period—6–9 months after a full course of immunization with mRNA vaccine, immune reactivity is present, but both cellular and humoral immune responses gradually decrease. The administration of a third dose mainly restores the specific humoral immune response against the SARS‐CoV‐2 virus.

In this study, we investigated the age-related dynamics in post-vaccine humoral immunity to diphtheria (DT) and tetanus (TT) toxoids in the Bulgarian population. In addition, we attempted to correlate the titers of specific antibodies with the predisposition to more common infectious pathology among our study participants. The 208 individuals tested were divided into five age groups: 0-4, 4-6, 6-12, 12-17 and 17-66 years, based on the vaccines received according to the immunization schedule in Bulgaria. Vaccine response was determined by measuring the concentrations of specific IgG antibodies using commercial ELISA kits. Sufficient protective levels of diphtheria (> 0.1 IU/mL) and tetanus (> 0.15 IU/mL) antitoxin were detected in 63.5% and 85.1% of all subjects, respectively. The highest rates of protection against both TT (94.3%) and DT (79.2%) were observed in the youngest age group (0-4 years). We also observed a relatively high rate of insufficient protection (< 0.1 IU/ml) against diphtheria (36% of individuals tested across all age groups) in comparison to tetanus (14.9% of all subjects). The rate of insufficient protection against both antigens was higher among children with frequent infections. Moreover, 77.1% of the individuals having low antibody titers against the highly immunogenic tetanus toxoid, also had low levels of diphtheria antibodies. The level of seroprotection is better for tetanus than for diphtheria toxoid at any age. In conclusion, our data provide information on the level of immunity to diphtheria and tetanus among vaccinated individuals in Bulgaria and allows for the identification of persons suspected of having an immune deficiency. Additional investigations are needed in order to provide reliable recommendations for the national vaccine program and personalized vaccinations.