Characterization of the TCRß repertoire of peripheral MR1-restricted MAIT cells in psoriasis vulgaris patients.

Psoriasis vulgaris (PV) is an inflammatory skin disease largely driven by aberrant αßT cells. Mucosal-associated invariant T (MAIT) cells, which constitute the largest circulating innate-like αßT cell community in human adults, are characterized by a semi-invariant TCRVα7.2 receptor and MR1-restricted affinity toward microbial metabolites. Limited MAIT TCRα diversity is complemented by a more variable TCRß repertoire, but its footprint in the MAIT repertoire of PV patients has never been tested. Here, we used bulk TCRSeq, MiXCR, VDJTools, and Immunarch pipelines to decipher and compare TCRß clonotypes from flow-sorted, peripheral TCRVα7.2+MR1-5-OP-RU-tet+MAIT cells from 10 PV patients and 10 healthy, matched controls. The resulting TCRß collections were highly private and individually unique, with small public clonotype content and high CDR3ß amino acid length variability in both groups. The age-related increase in the 'hyperexpanded' clonotype compartment was observed in PV, but not in healthy MAIT repertoires. The TCRß repertoires of PV patients were also marked by skewed TRBV/TRBJ pairing, and the emergence of PV-specific, public CDR3ß peptide sequences closely matching the published CDR3ß record from psoriatic skin. Overall, our study provides preliminary insight into the peripheral MAIT TCRß repertoire in psoriasis and warrants further evaluation of its diagnostic and clinical significance.

The miR-20a/miR-92b Profile Is Associated with Circulating γδ T-Cell Perturbations in Mild Psoriasis.

Psoriasis vulgaris (PV) is an autoinflammatory dermatosis of unknown etiology. Current evidence suggests a pathogenic role of γδT cells, but the growing complexity of this population has made the offending subset difficult to pinpoint. The work on γδTCRint and γδTCRhi subsets, which express intermediate and high levels of γδTCR at their surface, respectively, is particularly scarce, leaving their inner workings in PV essentially unresolved. We have shown here that the γδTCRint/γδTCRhi cell composition and their transcriptom are related to the differential miRNA expression by performing a targeted miRNA and mRNA quantification (RT-qPCR) in multiplexed, flow-sorted γδ blood T cells from healthy controls (n = 14) and patients with PV (n = 13). A significant loss of miR-20a in bulk γδT cells (~fourfold decrease, PV vs. controls) largely mirrored increasing Vδ1-Vδ2- and γδintVδ1-Vδ2- cell densities in the bloodstream, culminating in a relative excess of γδintVδ1-Vδ2- cells for PV. Transcripts encoding DNA-binding factors (ZBTB16), cytokine receptors (IL18R1), and cell adhesion molecules (SELPLG) were depleted in the process, closely tracking miR-20a availability in bulk γδ T-cell RNA. Compared to controls, PV was also associated with enhanced miR-92b expression (~13-fold) in bulk γδT cells that lacked association with the γδT cell composition. The miR-29a and let-7c expressions remained unaltered in case-control comparisons. Overall, our data expand the current landscape of the peripheral γδT cell composition, underlining changes in its mRNA/miRNA transcriptional circuits that may inform PV pathogenesis.

Differential Skewing of Circulating MR1-Restricted and γδ T Cells in Human Psoriasis Vulgaris.

Psoriasis vulgaris (PV) is a chronic, recurrent inflammatory dermatosis mediated by aberrantly activated immune cells. The role of the innate-like T cells, particularly gammadelta T (γδT) cells and MR1-restricted T lymphocytes, is incompletely explored, mainly through animal models, or by use of surrogate lineage markers, respectively. Here, we used case-control settings, multiparameter flow cytometry, 5-OP-RU-loaded MR1-tetramers, Luminex technology and targeted qRT-PCR to dissect the cellular and transcriptional landscape of γδ and MR1-restricted blood T cells in untreated PV cases (n=21, 22 matched controls). High interpersonal differences in cell composition were observed, fueling transcriptional variability at healthy baseline. A minor subset of canonical CD4+CD8+MR1-tet+TCRVα7.2+ and CD4+CD8-MR1-tet+TCRVα7.2+ T cells was the most significantly underrepresented community in male PV individuals, whereas Vδ2+ γδ T cells expressing high levels of TCR and Vδ1-δ2- γδ T cells expressing intermediate levels of TCR were selectively enriched in affected males, partly reflecting disease severity. Our findings highlight a formerly unappreciated skewing of human circulating MAIT and γδ cytomes during PV, and reveal their compositional changes in relation to sex, CMV exposure, serum cytokine content, BMI, and inflammatory burden. Complementing numerical alterations, we finally show that flow-sorted, MAIT and γδ populations exhibit divergent transcriptional changes in mild type I psoriasis, consisting of differential bulk expression for signatures of cytotoxicity/type-1 immunity (EOMES, RUNX3, IL18R), type-3 immunity (RORC, CCR6), and T cell innateness (ZBTB16).

Importance of the big-five in the future medical specialty preference.

BACKGROUND: The most crucial decision in the physician's career after graduation is undoubtedly the choice of specialization. It is conditioned by many factors such as intellectual challenges, clinical experience, economic and social influences. The aim of this study was to determine whether personality traits affect the choice of medical specialty at the University of Osijek, Croatia. METHODS: This cross-sectional study included a total of 407 medical students. To assess the personality traits, the IPIP Big-Five questionnaire was used. RESULTS: There were no differences in four of the five personality traits of the Big-Five questionnaire when comparing the groups based on their specialty preference: extroversion, agreeableness, conscientiousness, and emotional stability. A significant difference was found for openness to experience (intellect/imagination) trait, where students who preferred psychiatry specialties achieved the highest score, and those who chose public health specialties scored the lowest. We observed no significant effect between gender and specialty preference based on personality traits. CONCLUSIONS: We could not attribute the differences in personality traits to specialty preference. Medical students with higher scores on agreeableness and openness (intellect/imagination) scales were more inclined to psychiatric specialties, and more conscientiousness students preferred the anesthesiology and emergency medicine specialties. Even if variations in personality traits do not exist across different specialties, many other factors influence specialty preference.

Imbalanced concentrations of serum lipids and lichen planus.

The aim of this study was to analyze possible connection between the lichen planus and imbalanced concentrations of serum lipids and to evaluate the impact of various dietary regimes (used in the regulation of imbalanced concentrations of serum lipids) on the regression of lichen planus lesions. Research was conducted as a case-control study comprised of 72 patients with Lichen Planus and 30 participants from control group, treated at the Clinic for Dermatology and Venereology of the Clinical-Hospital Centre Osijek, Eastern Croatia, during 2010 and 2011. LP cases were diagnosed with both a clinical examination conducted by a dermatovenerology consultant and by patohistological diagnostic. Serum lipid levels (total cholesterol, LDL-cholesterol, triglycerides, HDL-cholesterol) were determined by the classic laboratory diagnostics in both investigated groups (LP patients and control group). The present study has confirmed that there is a strong connection between the imbalanced concentrations of one or more serum lipids (cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides) and the occurrence of LP which is important in the therapeutic approach to patients with this disease.

Genetic parameters of five new European Standard Set STR loci (D10S1248, D22S1045, D2S441, D1S1656, D12S391) in the population of eastern Croatia.

AIM: To establish allele frequencies and genetic parameters in eastern Croatia population and to compare them with those in other populations. The second aim was to compare the genetic profiles obtained with different forensic kits amplifying the same genetic markers. METHODS: Blood samples of 217 unrelated individuals from eastern Croatia were genotyped using AmpFlSTR NGM kit. Allele distribution and other genetic parameters were determined for 15 short tandem repeat (STR) loci, including the 5 loci recently added to the European Standard Set (ESS) of STR loci (D10S1248, D22S1045, D2S441, D1S1656, and D12S391). Ninety-six samples underwent duplicate analysis using AmpFlSTR Identifiler kit. RESULTS: Power of discrimination was highest for the two new ESS loci, D1S1656 (0.97254) and D12S391 (0.97339). Comparison of allele frequencies for 5 new ESS loci in our sample with previously published population data showed a significant difference from Maghreb population on D2S441 and from American Caucasian population on D1S1656. Comparison of allele frequencies for standard 10 STR loci with all the neighboring populations' data showed a significant difference only from Albanian population (on D2S1338, D18S51, and TH01). Discordant genotypes were observed in 5 (5.2%) samples at a single locus when amplified with both AmpFlSTR NGM and AmpFlSTR Identifiler kit. CONCLUSION: New ESS STR loci are highly polymorphic and short, and therefore very useful for the analysis of challenging forensic samples. DNA samples purposed for establishing databases should be routinely amplified in duplicate.