ABSTRACT
BACKGROUND: Periodontitis is a common oral disease caused by host inflammatory response towards bacteria biofilm. The chronic activation of immune response leads to destruction of teeth supporting tissue, bone loss and tooth detachment. Different factors could be involved in the development and severity of the disease; among them the host genetic background should be considered. OBJECTIVES: In our study, we analysed haploblocks in a genomic region within major histocompatibility complex (MHC) locus aimed at disclosing a possible correlation with the risk of periodontal disease in 602 adult subjects from North-East Italy. RESULTS: The CTTAC haploblock (formed by LTA-rs2857709, LTA-rs2844484, LTA- rs2229094, LTA-rs2229092 and LTA-rs1041981 polymorphisms) correlated with protection towards periodontitis condition, after regression analysis including age and smoking status as covariates (P-value = 0.015). CONCLUSION: Our results suggest that a haplotype within LTA gene (encoding for lymphotoxin alpha) is involved in the susceptibility towards chronic periodontitis.
Subject(s)
Chronic Periodontitis/genetics , Genetic Association Studies , Genetic Predisposition to Disease/genetics , Genome, Human/genetics , Haploidy , Lymphotoxin-alpha/genetics , Major Histocompatibility Complex/genetics , Adult , Aged , Chronic Periodontitis/immunology , Chronic Periodontitis/microbiology , Female , Genetic Loci/genetics , Humans , Inflammation , Italy , Male , Middle Aged , Risk , Severity of Illness IndexABSTRACT
We performed a retrospective genome-wide association study in HIV-infected individuals who were treated with dendritic cell-based immunotherapy in clinical trials performed by two research groups (Spain and Brazil). We aimed to identify host genetic variants influencing treatment response. The Illumina Human Core Exome 12 v 1.0 Bead Chip with over 250,000 markers was used to analyze genetic factors affecting treatment response. Additionally, we performed a meta-analysis of the results obtained from Spanish and Brazilian patients. We identified a genetic variation (rs7935564 G allele) in TRIM22 gene, which encodes TRIM22 protein acting like a HIV restriction factor, as being associated with good response to dendritic cell-based immunotherapy. We then verified the impact of TRIM22 rs7935564 SNP in susceptibility to HIV infection and disease progression by assessing the influence of biogeographic ancestry in the distribution of allelic and genotype frequencies in three populations from Italy, Brazil and Zambia. TRIM22 rs7935564 genotyping indicated association of G rs7935564 allele with long-term non-progression of HIV disease in Italian patients, thus corroborating our hypothesis that it is involved as a restriction factor in dendritic cell-based immunotherapy response. TRIM22 rs7935564 polymorphism was associated with good response to dendritic cell-based immunotherapy. We hypothesize that in selecting patients for treatment, there is a possible bias related to the natural presence of restriction factors that are genetically determined and could influence final outcome of therapy.
Subject(s)
Dendritic Cells/immunology , HIV Infections/therapy , HIV-1/immunology , Immunotherapy/methods , Minor Histocompatibility Antigens/genetics , Repressor Proteins/genetics , Tripartite Motif Proteins/genetics , Adult , Brazil , Child , Dendritic Cells/transplantation , Female , Gene Frequency , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , HIV Infections/immunology , Humans , Italy , Male , Polymorphism, Single Nucleotide , Retrospective Studies , Spain , Treatment OutcomeABSTRACT
OBJECTIVES: The aim of this study was to investigate whether dendritic cells (DCs) transfected with human secondary lymphoid-tissue chemokine (hSLC) and human interleukin-2 (hIL-2) genes are capable of improving DC's proliferation and to produce a marked antitumor effect in vitro combined with T-lymphocyte (TC). METHODS: SLC gene primer was designed based on the corresponding gene sequence in GenBank. The Kpn I site was introduced into the upstream of the primer and Xho I site into the downstream. The SLC gene was amplified with the template of pET32a(+)-SLC by polymerase chain reaction. SLC was cloned into pBudCE4.1/IL-2 (TRAIL was cut from pBudCE4.1/TRAIL- IL-2 before) to construct recombinant plasmid pBudCE4.1/SLC-IL-2(PSI). DCs were transfected with pBudCE4.1/SLC-IL-2 by gene electric transfection. Protein expression was determined with Western blot and enzyme-linked immunosorbent assays. Cytotoxicity of TC and DC against the human bladder tumor cell were examined by chromium release assay. Flow cytometric analyses were performed to determine the apoptosis of tumor cells and the percentage of Treg. RESULTS: A high level of expression of SLC and IL-2 was observed in DCs transfected with SLC and IL-2 genes. The mean production of IL-2 was 19.8 +/- 2.5, 511.10 +/- 52.36, and 541.3 +/- 62.04 ng/10(6) cells/24 hours in the DC/vector, DC/IL-2, and DC/SLC-IL-2, respectively. The mean SLC production was 29.8 +/- 4.43, 506.10 +/- 42.36, and 567.34 +/- 52.05 ngs/10(6)cells/24 hours in the DC/ vector, DC/SLC, and DC/SLC-IL-2, respectively. Cytotoxicity to bladder cancer cells was increased. The mean cytotoxicity (the effector/target ratio, 40:1) of TC-DC/parental, TC-DC/IL-2, TC-DC/SLC, and TC-DC/SLC-IL-2(TDSI) to the human bladder cancer cells was 32.1 +/- 5.5%, 63.5 +/- 6.6%, 78.1 +/- 9.63%, respectively. The apoptotsis rate of bladder cancer cells treated with TDSI was 18.6% by flow cytometry. Treg cells' percentage was very small in the DC medium. CONCLUSIONS: SLC and IL-2 were produced by autocrine in DCs transfected with SLC and IL-2 genes. DC/SLC-IL-2 can promote DC proliferation, while TC-DC/SLC-IL-2 and TC-DC/SLC could strongly enhance significant cytotoxicity against bladder cancer cell that was induced by the coculture of DCs (transfected with SLC and IL-2) and TC.
