The report and analysis concerning the usefulness of basic telemedicine tools in the skin cancer diagnostic screening process during COVID-19 pandemics.

Introduction: A rapid spread of the emerging COVID-19 pandemic limited the availability of professional medical advice. As a result, a significant increase in the number of undiagnosed and chronically ill patients without medical care was noticed. In reaction to the urgent need, the telemedical consultation, instead of the classical form, may be introduced as a vulnerable tool in preclinical evaluation of patients with potentially malignant skin lesions. Aim: In this study the results of the implementation of telemedical consultation programme with the intention to early detect the skin cancers in patients who, due to the COVID-19 pandemic, could not undergo the standard consultation was presented. Material and methods: The programme of remote dermatological consultation, which was introduced on 1 June 2020, covered all patients who had no possibility or will to visit the standard healthcare units. In case of suspicion of life-threatening skin lesions patients were invited for additional diagnostics or surgery. Obtained data, including demography, age, surgery description and pathomorphological examination were descriptively analysed. Results: In total, 80 consecutive patients were enrolled during the screening programme. In total, 31 lesions in 25 patients were excised. In this group there were 10 serious diagnoses including 5 cases of basal cell carcinoma, melanoma in situ and dysplastic nevi. Moreover, another 10 patients were referred to other specialists or specific recommendations were advised. Conclusions: An alternative track using teledermatology for patients with skin diseases was successfully introduced under the specific conditions of epidemiologic danger. Despite its disadvantages teledermatology enabled the diagnosis and treatment in a significant number of serious cases.

Metallic Orthodontic Materials Induce Gene Expression and Protein Synthesis of Metallothioneins.

BACKGROUND: Due to the long-term contact with metallic elements of orthodontic appliances, the potential influence of released metal ions on living organisms and the type of induced changes was investigated. MATERIALS AND METHODS: Twenty-four young domestic pigs classified in two groups (experimental and control) were chosen as the object of this study. In the experimental group of animals, two metal plates consisting of orthodontic bands representing the mass of orthodontic appliance were mounted on the internal side of the cheek for six months. The liver, lung, and brain samples were taken post mortem from animals of both groups. The gene expression of two isoforms of metallothionein (MT-1 and MT-2) were investigated using the qPCR technique. Protein expression was confirmed by the Western blot and ELISA techniques. RESULTS: The differences in metallothionein concentrations were observed in the lung and brain in the group of experimental animals, but not in the liver. The expression of MT-1 and MT-2 genes in the experimental vs. control group (respectively) was as follows: lung MT-1 1.04 vs. 1.11, MT-2 0.96 vs. 1.05, liver MT-1 0.89 vs. 0.91 vs. 1.12, MT-2 0.91 vs. 1.05, brain MT-1 1.24 vs. 1.20, and MT-2 0.955 vs. 0.945. These results were confirmed by gene activity, which was tested by qPCR. This increased the activity of metallothionein genes in the lungs and brain as a consequence of the release of metal ions into these tissues. The possible effects of detected change in metallothionein-2 gene expression could be the alteration of physiological functions of lung tissue. CONCLUSIONS: The effect of long-term exposure to metal orthodontic appliances on metallothioneins gene expression, as well as the induction of protein synthesis was proved.

Effects of traumatic life events, cognitive biases and variation in dopaminergic genes on psychosis proneness.

AIMS: Recent studies have provided evidence that interactions between variation in dopaminergic genes and stressful experiences might impact risk of psychosis. However, it remains unknown whether these interactions impact the development of subclinical symptoms, including psychotic-like experiences (PLEs). In this study, we aimed to test the effects of interactions between variation in dopaminergic genes and traumatic life events (TLEs) on a severity of PLEs. METHODS: We assessed TLEs, cognitive biases, PLEs as well as the catechol-O-methyltransferase (COMT) rs4680 and the dopamine D2 receptor (DRD2) rs6277 gene polymorphisms in 445 university students at three urban areas. RESULTS: There was a significant effect of the interaction between the COMT rs4680 and a history of any type of TLEs on a severity of PLEs. Among the COMT rs4680 Met allele carriers, a severity of PLEs was higher in individuals with a history of any type of TLEs. Further stratification of the sample revealed that this effect appears only in the group of participants with a high level of cognitive biases. The DRD2 rs6277 C allele was independently associated with a higher level of PLEs. CONCLUSIONS: Our results indicate that decreased dopamine catabolism related to the COMT gene polymorphism might increase psychosis proneness in individuals with a history of TLEs and high levels of cognitive biases. Variation in the DRD2 gene might exert independent effects on psychosis proneness. These findings imply that there are various levels of complexity in the models of interactions between genetic and environmental factors explaining the mechanisms underlying psychosis proneness.

Effects of interactions between variation in dopaminergic genes, traumatic life events, and anomalous self-experiences on psychosis proneness: Results from a cross-sectional study in a nonclinical sample.

BACKGROUND: There is a growing number of studies showing interactions between genetic polymorphisms associated with dopaminergic neurotransmission and traumatic life events (TLEs) on a risk of psychotic-like experiences (PLEs). Anomalous self-experiences (ASEs) have been associated both with TLEs as well as with PLEs. However, it remains unknown what is the role of ASEs in the complexity of gene-environment interactions on the emergence of PLEs. PATIENTS AND METHODS: We included 445 young adults-university students from three big cities in Poland. We used the Traumatic Events Checklist to assess TLEs, the Inventory of Psychotic-Like anomalous self-experiences in order to measure ASEs, and the Prodromal Questionnaire (PQ16) to record the level of PLEs. The following gene polymorphisms, related to dopaminergic neurotransmission, were determined: the catechol-O-methyltransferase (COMT) rs4680 polymorphism, the dopamine D2 receptor (DRD2) rs6277 polymorphism, and the dopamine transporter 1 (DAT1) rs28363170 polymorphism. RESULTS: There was a significant effect of the interaction between the DAT1 polymorphism, a severity of ASEs, and a history of TLEs on the level of PLEs. Among the DAT1 10R/10R homozygotes with low level of ASEs, a severity of PLEs was significantly higher in individuals with a history of any TLEs. Higher scores of the PQ16 were associated with a greater severity of ASEs both in the DAT1 9R allele carriers and the DAT1 10R/10R homozygotes. CONCLUSION: Our findings imply that genetic liability related to aberrant dopamine transport might impact the association between TLEs and PLEs in subjects with high levels of ASEs.

Additive manufacturing technologies enabling rapid and interventional production of protective face shields and masks during the COVID-19 pandemic.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through respiratory droplets and contact routes, hence the demand for personal protective equipment (PPE) has increased during the outbreak of coronavirus disease 2019 (COVID-19). Among the most noticeable shortages was the lack of face shields. The urgent demand for PPE induced interdisciplinary cooperation to overcome the shortages, and additive manufacturing proved to be ideal for the crisis situation. OBJECTIVES: To investigate the possibilities of implementing additive manufacturing technologies in the interventional fabrication of protective face shields for medical staff. MATERIAL AND METHODS: An Ender 3 Pro 3D printer was used to print headbands and Cura 4.4 was chosen as the slicing software. Open source face shield designs were downloaded as standard tessellation language (STL) files and compared. Only models with scientific support were taken under consideration. RESULTS: The mean time for producing the headbands tested ranged from 59 min to almost 3 h, depending on the design. After setting up our low budget printer and choosing the Prusa RC 3 protective face shield as the main product, we were able to fabricate about 30 face shields per week at a cost of about €1 each. During 4 weeks, 126 face shields were produced and delivered to various hospital wards, which substantially eased the shortages. CONCLUSIONS: Additive manufacturing enables immediate responses to needs in emergency situations, and allows for mass production of personal protective equipment in a short time due the rapid exchange of data among printer users. Despite the unregulated legal situation and insufficient scientific evidence, such protective equipment has been approved by clinicians and is currently used by medical personnel around the world.

Regulation of signaling pathways by Ampelopsin (Dihydromyricetin) in different cancers: exploring the highways and byways less travelled.

Ampelopsin or Dihydromyricetin is gradually emerging as a high-quality natural product because of its ability to modulate wide-ranging signaling pathways. Ampelopsin (Dihydromyricetin) has been reported to effectively modulate growth factor receptor (VEGFR2 and PDGFRß) mediated signaling,  TRAIL/TRAIL-R pathway, JAK/STAT and mTOR-driven signaling in different cancers. Ampelopsin (Dihydromyricetin) has also been shown to exert inhibitory effects on the versatile regulators which trigger EMT (Epithelial-to-Mesenchymal Transition). Findings obtained from in-vitro studies are encouraging and there is a need to comprehensively analyze how Ampelopsin (Dihydromyricetin) inhibits tumor growth in different cancer models. Better knowledge of efficacy of Ampelopsin (Dihydromyricetin) in tumor bearing mice will be helpful in maximizing its translational potential.

Urinary tract infections (UTIs) or genital tract infections (GTIs)? It's the diagnostics that count.

Urinary tract infections (UTIs) and genital tract infections (GTIs) are both very common infectious diseases. Thus, accuracy and rapidity in recognition and treatment of sexually transmitted urogenital tract infections (ST-UGTIs) is a major concern in global public health systems. The application of reliable, accurate diagnostic tools is the key to definite detection, identification and treatment. This literature review focused on different characteristics of UGTIs in patients and the importance of diagnostic methodologies. The articles published and indexed from 1980 through October 2018 in the databases of PubMed and MEDLINE, as well as the Google Scholar web search engine, were collected and studied. MeSH keywords of "Sexual intercourse", "Urinary Tract Infections", "Genital Tract Infections" and "Toll-Like Receptors" were used for searching articles. Then, the proper articles (original and review articles) were subjected to a very rigorous selection process. The clinical symptoms and signs or asymptomatic properties of UTIs and GTIs are similar and often overlap. In many cases, the lack of suitable diagnostic techniques leads to misdiagnosed/undignosed GTIs and overdiagnosed UTIs. The outcome of poor diagnostics is failure of definite identification and treatment. The application of advanced techniques comprising PCR, microarray and next-generation sequencing promises to be more effective, together with the use of the microbial pattern of the individual's UGT to provide reliable detection, identification and definite treatment. This will be an option in the near future.

Paediatric-onset and adult-onset Graves' disease share multiple genetic risk factors.

BACKGROUND: Graves' disease (GD) is an autoimmune thyroid disease (AITD) with a peak incidence between 30 and 50 years of age. Although children and adolescents may also develop the disease, the genetic background of paediatric-onset GD (POGD) remains largely unknown. Here, we looked for similarities and differences in the genetic risk factors for POGD and adult-onset GD (AOGD) as well as for variants associated with age of GD onset. MATERIALS AND METHODS: A total of 1267 GD patients and 1054 healthy controls were included in the study. Allele frequencies of 40 established and suggested GD/AITD genetic risk variants (39 SNPs and HLA-DRB1*03) were compared between POGD (N = 179), AOGD (N = 1088) and healthy controls. Subsequently, multiple linear regression was used to explore the relationship between age of GD onset and genotype for each locus. RESULTS: We identified six POGD risk loci, all of them were also strongly associated with AOGD. Although for some of the analysed variants, including HCP5 (rs3094228), PRICKLE1 (rs4768412) and SCGB3A2 (rs1368408), allele frequencies differed nominally between POGD and AOGD patients, these differences were not significant after applying multiple testing correction (Pcor  = 0.05/40 = 1.25 × 10-3 ). Regression analysis showed that patients with higher number of HCP5 risk alleles tend to have a significantly earlier onset of GD (P = 6.9 × 10-5 ). CONCLUSIONS: The results of our study revealed that POGD and AOGD share multiple common genetic risk variants. Moreover, we demonstrated for the first time that HCP5 polymorphism is associated with an earlier age of GD onset in a dose-dependent manner.

Epitopes identified in GAPDH from Clostridium difficile recognized as common antigens with potential autoimmunizing properties.

Clostridium difficile (CD) infections are a growing threat due to the strain resistance to antibiotic treatment and the emergence of hypervirulent strains. One solution to this problem is the search for new vaccine antigens, preferably surface-localized that will be recognized by antibodies at an early stage of colonization. The purpose of the study was to assess the usefulness of novel immunoreactive surface proteins (epitopes) as potential vaccine antigens. Such approach might be tough to pursue since pathogens have acquired strategies to subvert adaptive immune response to produce humoral response against non-essential proteins for their survival. In this study CD surface proteins were isolated, immunoreactive proteins identified and mapped to select potential epitopes. The results of the study exclude the use of CD glyceraldehyde 3-phosphate dehydrogenase as a vaccine antigen, especially as a whole protein. Sequences P9 (201AAGNIVPNTTGAAKAI218) and P10 (224KGKLDGAAQRVPVVTG241) recognized by patients sera are conserved and widespread among CD strains. They show cross-reactivity with sera of people suffering from other bacterial infections and are recognized by sera of autoimmune disease patients. Our study documents that special care in analyzing the sequence of new epitope should be taken to avoid side effects prior to consider it as a vaccine antigen.

Profiling inflammatory signatures of schizophrenia: A cross-sectional and meta-analysis study.

We aimed to profile a broad panel of inflammatory markers in patients with schizophrenia and healthy controls. Additionally, we performed a meta-analysis of chemokine alterations that have not been subjected to quantitative synthesis so far. We recruited 78 patients with schizophrenia and 78 healthy controls, and measured inflammatory markers using the Luminex technology. After adjustment for multiple testing, we found elevated levels of interleukin (IL)-1 receptor antagonist (IL-1RA), IL-6, IL-7, IL-8, IL-9, IL-10, IL-13, interferon-γ, eotaxin-1, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), platelet-derived growth factor with two B subunits (PDGF-BB), macrophage inflammatory protein (MIP)-1α, MIP-1ß, vascular endothelial growth factor A (VEGF-A) and RANTES in multiple-episode schizophrenia (MES) patients. These differences, except for the difference in eotaxin-1 levels, appeared to be significant after co-varying for the dosage of antipsychotics. There were no significant differences in the levels of immune markers between first-episode schizophrenia (FES) patients and controls. Our meta-analysis revealed elevated levels of MCP-1 in first-episode psychosis (FEP) patients and MES individuals. Other chemokine alterations (elevated levels of IL-8, eotaxin-1 and MIP-1ß) were present only in MES patients. Our results indicate that dysregulation of immune response in schizophrenia develops with illness progression or appears as a long-term medication effect. Chemokine alterations are another example of aberrant immune response in schizophrenia patients. Elevated levels of MCP-1 might represent trait markers since these alterations were found in FEP and MES patients. Other chemokine alterations might be the markers of disease progression or might represent medication effects.

The Influence of Genetic Variations in the CD86 Gene on the Outcome after Allogeneic Hematopoietic Stem Cell Transplantation.

CD86 molecule is the ligand for both costimulatory (CD28) and coinhibitory (CTLA-4) molecules, and it regulates immune response after allogeneic hematopoietic stem cell transplantation (alloHSCT). Therefore, we postulate that CD86 gene variations might influence the outcome after alloHSCT. Altogether, 295 adult patients (pts) undergoing related (105 pts) and unrelated (190 pts) donor-matched HSCT were genotyped for the following CD86 gene polymorphisms: rs1129055, rs9831894, and rs2715267. Moreover, the donors' rs1129055 polymorphism was determined. None of the investigated SNPs alone were associated with aGvHD and rate of relapse. However, we showed that rs2715267 SNP influenced overall survival (OS) after alloHSCT. The 24-month OS for the rs271526GG recipients was worse than that for the recipients possessing T allelle (TT or GT genotypes) (p = 0.009). Moreover, analysis of gene-gene interaction between CD86 and CTLA-4 showed that having both the A allele for CD86 rs1129055 and the CTLA-4 CT60GG genotype in recipients increased the risk of aGvHD about 3.5 times. Interestingly, the donors' rs1129055GG genotype and the recipients' CT60GG genotype also increased the risk of aGvHD about 2.7-fold. We postulate that recipients' CD86 gene polymorphisms influence the overall survival after alloHSCT and, together with CTLA-4 polymorphisms, might be considered a risk factor for aGvHD.

Polymorphisms in immune-inflammatory response genes and the risk of deficit schizophrenia.

Polymorphisms in immune-inflammatory response genes are believed to impact schizophrenia susceptibility. However, it remains unknown whether immunogenetic factors play a role in the etiology of deficit schizophrenia (D-SCZ). Therefore, we genotyped four polymorphisms in genes encoding two immune system regulatory proteins (CTLA-4 rs231775 and CD28 rs3116496), interleukin-6 (IL6 rs1800795) and transforming growth factor-ß (TGFB1 rs1800470) in 513 schizophrenia patients and 374 controls. The CD28 rs3116496-CC genotype and C-allele were significantly more frequent in the whole group of patients and D-SCZ patients compared to controls. Our results indicate that the CD28 rs3116496 polymorphism might impact the risk of schizophrenia, especially D-SCZ.

PD-1 gene polymorphic variation is linked with first symptom of disease and severity of relapsing-remitting form of MS.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), where inflammation, demyelination together with the axonopathy are the cardinal features on pathologic ground, with a combined genetic and environmental background. The associations of PD-1 single nucleotide polymorphisms (SNPs): PD-1.3 (in intron 4), PD-1.5 and PD-1.9 (both in exon 5) with clinical manifestation of MS in 479 south Polish individuals including 203 MS patients were analyzed. Presence of PD-1.5T allele was linked with the first manifestations of disease: diplopia and pyramidal signs - favored pyramidal signs but protected against of diplopia development. Farther, PD-1.3G/PD-1.5C/PD-1.9C haplotype significantly favored whereas GTC protected against diplopia. Besides, GTT haplotype strongly favored non-severe RRMS outcome and ATC haplotype was specific only for these MS patients. Our population-based case-control study, investigating selected three PD-1 SNPs: PD-1.3, PD-1.5 and PD-1.9, revealed that polymorphic variation may be rather disease-modifying than MS risk factor.

Gender-dependent and age-of-onset-specific association of the rs11675434 single-nucleotide polymorphism near TPO with susceptibility to Graves' ophthalmopathy.

The role of TPO gene polymorphism in the susceptibility to Graves' disease (GD) remains unclear. However, single-nucleotide polymorphisms (SNPs) near TPO have been recently associated with serum levels of thyroid peroxidase (TPO) antibody in two independent genome-wide association studies. Moreover, we have observed a strong association between the rs11675434 SNP located near TPO and the presence of clinically evident Graves' ophthalmopathy (GO). The aim of the current study was to reevaluate and dissect this association in an extended group of 1231 well-characterized patients with GD (1043 adults and 188 children) and 1130 healthy controls from the Polish Caucasian population, considering possible gender-dependent and age-of-onset-specific effects of the studied SNP. We found that the T allele of rs11675434 was significantly more frequent in GD patients with than without GO (odds ratio (OR)=1.26, 95% confidence interval (CI)=1.05-1.51, P=0.012), which was consistent with our previous findings. Further analyses performed in subgroups of patients showed that the association with GO was significant in adult patients with age of GD onset ⩾45 years (OR=1.34, 95% CI=1.03-1.75, P=0.031), but not in children and adolescents or adult patients with earlier onset of the disease (OR=1.72, 95% CI=0.77-3.84, P=0.18 and OR=1.05, 95% CI=0.79-1.40, P=0.75, respectively). Moreover, a strong association with GO was present in males (OR=2.06, 95% CI=1.40-3.02, P=0.0002), whereas it was absent in females (OR=1.10, 95% CI=0.90-1.35, P=0.35). The results of our study further suggest that rs11675434 SNP located near TPO is associated with the development of GO, especially in males and patients with later age of GD onset.

CD28/CTLA-4/ICOS haplotypes confers susceptibility to Graves' disease and modulates clinical phenotype of disease.

Graves' disease, an autoimmune disease with heterogeneous symptoms including Graves' orbitopathy, has a combined genetic/environmental background, where variations within CD28/CTLA-4/ICOS genes are considered as disease markers.Association of CD28c.17+3T>C(rs3116496), CTLA-4g.319C>T(rs5742909), CTLA-4c.49A>G(rs231775), CTLA-4g.*642AT(8_33), CT60(rs3087243), Jo31(rs11571302), ICOSc.1554+4GT(8_15) polymorphisms with susceptibility to Graves' disease and clinical outcome was investigated. The study group comprised of 561 Polish Caucasians, including 172 unrelated Graves' disease patients. CTLA-4c.49A>G, CTLA-4g.319C>T, and CT60 were genotyped by PCR-RFLP; Jo31 and CD28c.17+3C>T by minisequencing; CTLA-4g.*642AT(8_33) and ICOSc.1554+4GT(8_15)-PCR and fluorescence-based technique. CD28c.17+3T>C(rs3116496)T/CTLA-4g.319C>T(rs5742909)C/CTLA-4c.49A>G(rs231775)G/CTLA-4g.*642AT(8_33)(AT16-21)/CT60(rs3087243)G/Jo31(rs11571302)G/ICOSc.1554+4GT(8_15)(m) and TCA(AT<16)GT(m) haplotypes increased risk of Graves' disease, especially in males, as well as overall Graves' orbitopathy development with severe outcome. TCG(AT16-21)GG(l) haplotype increased risk of Graves' disease and reduced the chance of successful medical treatment. Although this haplotype was mainly observed in patients without signs of Graves' orbitopathy, if Graves' orbitopathy developed it favored a Graves' orbitopathy outcome. Haplotype TCA(AT>21)GT(m) increased Graves' disease risk in women and, in all patients, was linked to Graves' disease without Graves' orbitopathy. TCG(AT<16)GG(m) haplotype was predominantly observed in patients without Graves' orbitopathy, whereas TCA(AT16-21)GG(m) was absent in those patients. TCA(AT16-21)GG(m) occurred in patients with a mild Graves' orbitopathy outcome. The marker CTLA-4g.*642AT(8_33) was the only independent Graves' disease risk factor, whereas CT60 was an independent factor for disease progression. Sporadic Graves' disease was related to presence of CTLA-4c.49A>G[A] and the rare CTLA-4g.319C>T[T] allele variant. Familial background of the disease was exclusively associated with CTLA-4g.*642AT(8_33)[AT>21]/[AT>21] genotype. CD28/CTLA-4/ICOS loci may confer inherited susceptibility to Graves' disease or may be involved in susceptibility to Graves' disease and play a pathogenetic role.

Intragenic Variations in BTLA Gene Influence mRNA Expression of BTLA Gene in Chronic Lymphocytic Leukemia Patients and Confer Susceptibility to Chronic Lymphocytic Leukemia.

The aim of this study was to determine the association between polymorphisms in gene encoding B- and T-lymphocyte attenuator (BTLA) and susceptibility to chronic lymphocytic leukemia (CLL) and their influence on mRNA expression of BTLA gene in T and B cells from CLL patients (pts.). The following BTLA single-nucleotide polymorphisms (SNPs): rs2705511, rs1982809, rs9288952, rs76844316, rs16859633, rs9288953, rs2705535, rs1844089, rs2705565, rs2633580 were genotyped with use of TaqMan probes in 321 CLL pts. and in 470 controls. The mRNA levels of human BTLA were determined in subpopulations of T and B cells from 37 CLL patients with use of Applied Biosystems assays. Three SNPs: rs1982809, rs2705511 and rs9288953 were associated with susceptibility to CLL. The frequency of rs1982809[G] allele and rs2705511[C] allele carriers was higher in patients compared to the controls (0.51 vs. 0.41, OR 1.51, 95% CI 1.14-2.02, p = 0.004 and 0.56 vs. 0.44, OR 1.62, 95% CI 1.22-2.16, p = 0.0009, respectively). Furthermore, rs9288953[TT] genotype was overrepresented in CLL pts. compared to the controls (0.22 vs. 0.14, OR 1.74, 95% CI 1.20-2.53, p = 0.004). The evaluation of the influence of BTLA SNPs on BTLA mRNA expression in CLL pts. showed that the presence of rs1982809[G] allele was associated with lower median (±SD) BTLA mRNA expression in T cells (expressed as 2-delta Ct) in CLL pts. as compared to [AA] homozygotes (0.009 ± 0.013 vs. 0.026 ± 0.012, p = 0.03). Our results indicate that rs1982809 BTLA gene polymorphism is associated with mRNA expression level and that variations in the BTLA gene might be considered as potentially low-penetrating CLL risk factor.

Polymorphisms in CD28, CTLA-4, CD80 and CD86 genes may influence the risk of multiple sclerosis and its age of onset.

CD28/CTLA-4­CD80/CD86 molecules play an important role in the regulation of T cells activation. Defects in proteins involved in this pathway may lead to the development of autoimmune diseases in which T cells are involved. In this case­control study (336 multiple sclerosis (MS) patients and 322 controls) we investigated the possible association of eleven polymorphisms in CD28, CTLA-4, CD80 and CD86 genes with susceptibility to MS and/or its progression. We also took into account HLA-DRB1*15:01 status. Moreover, this study aimed to determine the possible gene-gene interactions between examined SNPs associated with the susceptibility to MS and its outcome. Our investigation revealed that in HLA-DRB1*15:01 negative individuals, G allele in rs231775A NGof CTLA-4 gene was associatedwith higher risk ofmultiple sclerosis. Additionally, the association of rs2715267T NGof CD86 gene withMS susceptibilitywas detected. In details, carriers of G allele at this polymorphic site possessed higher risk of MS in comparison to TT homozygotes. On the other hand, the lower risk of MS was observed in individuals carrying A allele at the rs1599795T N A polymorphic site of CD80. Furthermore, the analysis revealed an interaction between three polymorphisms: rs3116496T N C (CD28), rs6641T N G (CD80) and rs17281995G N C (CD86), associated with the age of MS onset.

CTLA4 and CD28 Gene Polymorphisms with Respect to Affective Symptom Domain in Schizophrenia.

BACKGROUND: Accumulating evidence indicates that immune alterations in schizophrenia are due to genetic underpinnings. Here, we aimed at investigating whether polymorphisms in CTLA4 and CD28 genes, encoding molecules that regulate T-cell activity, influence schizophrenia symptomatology. METHOD: We recruited 120 schizophrenia patients and 380 healthy age- and sex-matched controls. We divided the patients into two groups: one with no co-occurrence between psychotic and affective symptoms and the second one with psychotic symptoms dominating in the clinical manifestation, although also with occasional affective disturbances in the course of illness. RESULTS: Among the patients with co-occurring affective symptoms, there were significantly more CTLA4 c.49A>G[A] alleles (p = 0.018, odds ratio (OR) 2.03, 95% confidence interval (CI) 1.2-3.66) and more CTLA4 g.319C>T[T] alleles (p = 0.07, OR 1.93, 95% CI 0.94-4.13) in comparison to the second group. Additionally, we have shown that CD28 c.17 + 3T>C[C+] were more significantly overrepresented among patients with co-occurring psychotic and affective symptoms (p = 0.0003, OR 3.36, 95% CI 1.69-6.68) than in patients without co-occurence between these symptoms (p = 0.012, OR 1.88, 95% CI 1.15-3.10). CONCLUSION: CTLA4 and CD28 gene polymorphisms may not only act in immune deregulation observed in schizophrenia, but may also influence the course of the illness by modifying the susceptibility to the co-occurrence of psychotic and affective symptoms.

A CT60G>A polymorphism in the CTLA-4 gene of the recipient may confer susceptibility to acute graft versus host disease after allogeneic hematopoietic stem cell transplantation.

T cell activation plays a crucial role in the development of acute graft versus host disease (aGvHD). Cytotoxic T cell antigen-4 (CTLA-4) is a co-inhibitory molecule that negatively regulates T cell activation, differentiation, and proliferation. Single-nucleotide polymorphisms (SNPs) in CTLA-4 gene may affect its function. Inconsistent observations have been reported regarding the associations of CTLA-4 SNPs with complications after hematopoietic stem cell transplantation (HSCT). Moreover, the majority of the observations were focused on the donors' SNPs. Recently, a few studies have shown that recipients' genetic variations in the CTLA-4 gene might influence HSCT results. The aim of our study was to determine the influence of the CTLA-4 gene polymorphisms of the donors and the recipients on the outcome of HSCT. Altogether, 312 donor-recipient pairs were genotyped for the CTLA-4c.49A>G (rs231775) and CT60G>A (rs3087243) SNPs using the TaqMan®SNP Genotyping Assays. In this study, it was shown that the recipients' CT60G>A[GG] genotype, the myeloablative conditioning regimen, and HSCT from an unrelated donor were independent aGvHD risk factors (odds ratio (OR) 2.63, 95% confidence intervals (95% CI) 1.45-4.59, p = 0.001; OR 2.68, 95% CI 1.65-4.07, p = 0.00003; and OR 1.87, 95 % CI 1.02-3.24, p = 0.04, respectively). Moreover, haplotype analysis revealed that possessing allele A in both of the SNPs decreased the risk of aGvHD approximately 1.5-fold (RR 0.69, p = 0.008). Our data suggest that the CT60G>A[GG] genotype in the recipient has an impact on aGvHD development, especially in patients receiving transplants from unrelated donors together with the myeloablative conditioning regimen.