The Impact of Th1/Th2 Response Variations on Risk of Developing Childhood Leukaemia: A Pilot Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 849-849
Author(s):  
Zara M. Josephs ◽  
David Gonzalez de Castro ◽  
David C. Johnson ◽  
Astrid Novosel ◽  
Arndt Borkhardt ◽  
...  
Keyword(s):  
Immune Response ◽  
Bone Development ◽  
Infectious Agent ◽  
T Cell Subsets ◽  
Immune Response Gene ◽  
Childhood Leukaemia ◽  
Nucleotide Polymorphisms ◽  
Th2 Response ◽  
Delayed Infection ◽  
The Impact

Abstract The delayed infection hypothesis, first proposed by Mel Greaves in 1988, postulates that paediatric leukaemia is the result of a triggering infectious agent acting upon an unconditioned immune system. According to this hypothesis, childhood leukaemia develops in two sequential steps involving (i) the generation, in utero, of a pre-leukaemic clone; and (ii) the post-natal conversion, by an infectious agent, of this pre-leukaemic clone into a leukaemic transformant. The balance between the two major T cell subsets, Th1 and Th2, is critical for determining the type and extent of the human immune response. Children shielded early in life from common childhood infections have unconditioned immune systems showing Th1/Th2 anomalies that may pre-dispose them to developing leukaemia. Since the delayed infection hypothesis specifically proposes that the immune response to infection critically determines leukaemia development, we are studying genes encoding cytokines that affect this balance. We are looking for patterns of single nucleotide polymorphisms (SNPs) in paediatric acute lymphoblastic leukaemia (ALL) and comparing these with the patterns in non-ALL controls. Our aims in this study are to collect and catalogue archived paediatric ALL and non-ALL control DNA samples from centres around Europe; to expand the collected stocks by whole genome amplification (WGA); and to determine the combination of immune response gene-related SNPs in paediatric ALL and non-ALL patients while piloting a high-throughput protocol for determining patterns of SNPs in multiple genes. Using the Taqman and SNPlex assays, we aim to evaluate relevant genes including the ones encoding interleukin (IL)-12, IL-10, IL-2, IL-4, interferon-γ and IFNγ receptor, all known to regulate Th1/Th2 balance. 300 paediatric ALL and 200 non-ALL control DNA samples were obtained from sample banks in the Royal Marsden Hospital in London and the Kinderspital in Munich. 90% of samples were successfully amplified from nanogram to microgram quantities using the GenomiPhi® WGA kit. Up to 1000-fold amplification was routinely achieved using this method, with a mean of 600-fold amplification. DNA fragments from samples were amplifiable by multiplex PCR using primers to five genomic regions (corresponding to AF4, PLZF, RAG1 and TBXAS1). In addition, sequencing of 700-bp amplicons from the IL-10, IL-18 and ERCC2 genes showed identity of pre- and post-GenomiPhi templates for the fragments sequenced, confirming that the products of WGA by this method are representative of the original templates. We will present data on our SNPlex analysis of 66 t(12;21)- and 84 hyperdiploidy-related paediatric ALL samples, together with 135 untyped samples, compared to 200 control samples, for 6 Th1/Th2-related genes. We will also present similar comparative data on 70 SNPs in 50 genes connected with DNA repair, xenobiotic metabolism, oxidative stress, neuropathies and bone development, as well as a control set of genes unrelated to leukaemia. Kay Kendall Leukaemia Fund

scholarly journals Infection with the Helminth Nippostrongylus brasiliensis Does Not Interfere with Efficient Elimination of Mycobacterium bovis BCG from the Lungs of Mice

2002 ◽  
Vol 9 (3) ◽  
pp. 727-730 ◽  
Author(s):  
Klaus J. Erb ◽  
Claudia Trujillo ◽  
Mike Fugate ◽  
Heidrun Moll
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Mycobacterium Bovis ◽  
Helminth Infection ◽  
Nippostrongylus Brasiliensis ◽  
Th2 Response ◽  
Th2 Responses ◽  
The Impact ◽  
Th1 Immune Response

ABSTRACT Infection with Mycobacterium tuberculosis continues to be one of the major global health threats. Strong mycobacterium-specific Th1 immune responses correlate with protection, and decreased Th1 responses correlate with disease progression. In contrast, the impact of Th2 responses on the development of protective immune responses to mycobacteria remains unclear. To analyze whether ongoing Th2 responses present in the lung influence the development of a protective Th1 immune response to mycobacteria, we coinfected mice with the helminth Nippostrongylus brasiliensis and Mycobacterium bovis BCG. We found that the T cells from the lymph nodes of coinfected mice secreted significantly less gamma interferon than did the T cells from mice infected with M. bovis BCG after in vitro stimulation with purified protein from M. tuberculosis when 108 CFU of M. bovis BCG were used for the infection. This result indicates that the helminth infection reduced the Th1 immune response to the mycobacteria in the lung. However, mycobacterial clearance was not delayed in the coinfected animals. Importantly, the infection with BCG after the helminth infection did not reduce the helminth-induced Th2 response in the lung, ruling out the possibility that the lack of a reduction in bacterial clearance in the coinfected mice was due to a downmodulation of the helminth-induced Th2 response. Taken together, our results suggest that ongoing Th2 responses in the lung do not necessarily lead to increased susceptibility to mycobacterial infection.

scholarly journals SARS-CoV-2 cellular immune response in uninfected health care workers with prolonged and close exposure to COVID-19 patients

2020 ◽  
Author(s):  
Alejandro Vallejo ◽  
Pilar Vizcarra ◽  
Carmen Quereda ◽  
Ana Moreno ◽  
Jose L Casado
Keyword(s):  
Health Care ◽  
Immune Response ◽  
Health Care Workers ◽  
Cellular Immune Response ◽  
Cellular Response ◽  
Cytokine Production ◽  
Th2 Response ◽  
Care Workers ◽  
Cellular Immune ◽  
The Impact

Abstract Health care workers (HCW) are at an increased risk since they are directly exposed to SARS-CoV-2 infected patients, nevertheless, some remained without the development of anti-SARS-CoV-2 antibodies, suggesting lesser susceptibility to infection1-5. This study aimed to ascertain a potential specific cellular immune response to SARS-CoV-2 in these largely exposed HCWs.In this cross-sectional, case-control study, we analyzed 39 exposed uninfected HCWs and 17 convalescent HCWs. Cellular immune response was evaluated after SARS-CoV-2 stimulation with peptide pools (proteins S, M, and N), using bead-based multiplex assay (12 cytokines).Overall, 94.8% of uninfected HCWs had some degree of specific cellular response to SARS-CoV-2 structural proteins that could be classified, according to the number of cytokine production, as strong (61.5%), partial (33.3%), and weak/no response (5.1%). Strong responders showed a higher anti-inflammatory cytokine production (IL5 and IL10, p<0.001 and 0.002, respectively), and similar (IFN-γ and TNF-α, p=0.435 and 0.532, respectively) or higher (IL12, p=0.021) pro-inflammatory production compared to convalescents, resulted in a predominantly Th2 response. This study demonstrated a consistent and polyfunctional immune cellular response after stimulation with SARS-CoV-2 peptides in extensively exposed individuals that should be considered to establish the infection susceptibility, the impact in herd immunity, and the risk of relapses.

scholarly journals Effects of Lipopolysaccharide-Binding Protein (LBP) Single Nucleotide Polymorphism (SNP) in Infections, Inflammatory Diseases, Metabolic Disorders and Cancers

2021 ◽  
Vol 12 ◽  
Author(s):  
Leilei Meng ◽  
Zichen Song ◽  
Anding Liu ◽  
Uta Dahmen ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Immune Response ◽  
Metabolic Disorders ◽  
Inflammatory Diseases ◽  
Binding Protein ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Main Component ◽  
The Impact ◽  
Lps Binding

Inflammation, which is induced by the immune response, is recognized as the driving factor in many diseases, including infections and inflammatory diseases, metabolic disorders and cancers. Genetic variations in pivotal genes associated with the immune response, particularly single nucleotide polymorphisms (SNPs), may account for predisposition and clinical outcome of diseases. Lipopolysaccharide (LPS)-binding protein (LBP) functions as an enhancer of the host response to LPS, the main component of the outer membrane of gram-native bacteria. Given the crucial role of LBP in inflammation, we will review the impact of SNPs in the LBP gene on infections and inflammatory diseases, metabolic disorders and cancers.

scholarly journals The Influence of Psychological Stress on HPV Infection Manifestations and Carcinogenesis

2021 ◽  
Vol 55 (S2) ◽  
pp. 71-88
Keyword(s):  
Immune Response ◽  
Psychological Stress ◽  
Stress Hormones ◽  
Cervical Dysplasia ◽  
Hpv Infection ◽  
Virus Genome ◽  
Th2 Response ◽  
Study Results ◽  
E6 And E7 ◽  
The Impact

Psychological stress is an important factor involved in disease manifestations of human papillomavirus (HPV) infection, and it can participate in HPV-associated carcinogenesis. The impact or effect which stress can have (exert) depends on a person’s genetic pool, experiences and behaviors. Due to inconsistencies in some study results, this issue remains a subject of research. Concerning the course of HPV manifestations, it has been observed that a higher number of life stressors in at least the previous 6 months, the absence of social support and the types of personal coping mechanisms employed, all influence HPV progression. In women with cervical dysplasia, a connection between greater stress experiences and dysregulation of specific immune responses has been observed. Once HPV enters a cell via the α6 integrin there are three possible sequences: latent infection, subclinical infection, and clinically manifest disease. HPV proliferation in differentiated epithelial cells induces morphologically cytopathic changes (koilocytosis, epidermal thickening, hyperplasia, hyperkeratosis). Oncogenic transformation requires the integration of the virus genome into the host genome. In doing so, DNA in the E1 region of E2 breaks down, leading to transcription disorders of E6 and E7. For the formation of irreversible malignancy, the following sequence is necessary: initial expression of E6 and E7 genes followed by suppression of apoptosis and the stabile expression of E6 and E7 proteins that protect transformed cells from apoptosis. A successful immune response is characterized by a strong, local cell-mediated immune response. Several factors are important for the regression of HPV manifestation/infection, among which is psychological stress which can prolong the duration and severity of HPV disease. Stress hormones may reactivate latent tumor viruses, stimulate viral oncogene expression, and inhibit antiviral host responses. In the regression of HPV infection, increased activity of Th1 cells was observed. However, during psychosocial stress, a decrease in the Th1 type of immune response is seen, and there is a shift towards a Th2 response. Understanding perceived stress and biological changes in stress, as well as the evaluation of immune parameters, gives researchers a better picture of how stress influences HPV infections and how to improve disease management and outcomes.

scholarly journals Impact of PD-1 gene polymorphism and its interaction with tea drinking on susceptibility to tuberculosis

2021 ◽  
Vol 149 ◽  
Author(s):  
Jing Wang ◽  
Mian Wang ◽  
Zihao Li ◽  
Xinyin Wu ◽  
Xian Zhang ◽  
...  
Keyword(s):  
Case Control Study ◽  
Preventive Measures ◽  
Nucleotide Polymorphisms ◽  
Unconditional Logistic Regression ◽  
Negative Interaction ◽  
Single Nucleotide ◽  
High Risk Populations ◽  
Tea Drinking ◽  
The Impact ◽  
Control Study

Abstract The aim of this study was to explore the impact of polymorphism of PD-1 gene and its interaction with tea drinking on susceptibility to tuberculosis (TB). A total of 503 patients with TB and 494 controls were enrolled in this case–control study. Three single-nucleotide polymorphisms of PD-1 (rs7568402, rs2227982 and rs36084323) were genotyped and unconditional logistic regression analysis was used to identify the association between PD-1 polymorphism and TB, while marginal structural linear odds models were used to estimate the interactions. Genotypes GA (OR 1.434), AA (OR 1.891) and GA + AA (OR 1.493) at rs7568402 were more prevalent in the TB patients than in the controls (P < 0.05). The relative excess risk of interaction (RERI) between rs7568402 of PD-1 genes and tea drinking was −0.3856 (95% confidence interval −0.7920 to −0.0209, P < 0.05), which showed a negative interaction. However, the RERIs between tea drinking and both rs2227982 and rs36084323 of PD-1 genes were not statistically significant. Our data demonstrate that rs7568402 of PD-1 genes was associated with susceptibility to TB, and there was a significant negative interaction between rs7568402 and tea drinking. Therefore, preventive measures through promoting the consumption of tea should be emphasised in the high-risk populations.

scholarly journals Recruitment and Expansion of Tregs Cells in the Tumor Environment—How to Target Them?

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1850
Author(s):  
Justine Cinier ◽  
Margaux Hubert ◽  
Laurie Besson ◽  
Anthony Di Roio ◽  
Céline Rodriguez ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Poor Prognosis ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Major Function ◽  
Normal Tissues ◽  
Tumor Environment ◽  
Plastic Transformation

Regulatory T cells (Tregs) are present in a large majority of solid tumors and are mainly associated with a poor prognosis, as their major function is to inhibit the antitumor immune response contributing to immunosuppression. In this review, we will investigate the mechanisms involved in the recruitment, amplification and stability of Tregs in the tumor microenvironment (TME). We will also review the strategies currently developed to inhibit Tregs’ deleterious impact in the TME by either inhibiting their recruitment, blocking their expansion, favoring their plastic transformation into other CD4+ T-cell subsets, blocking their suppressive function or depleting them specifically in the TME to avoid severe deleterious effects associated with Treg neutralization/depletion in the periphery and normal tissues.

scholarly journals PSI-40 Two mitochondrial lineages revealed in North American yak

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 477-477
Author(s):  
Leah K Treffer ◽  
Edward S Rice ◽  
Anna M Fuller ◽  
Samuel Cutler ◽  
Jessica L Petersen
Keyword(s):  
Sequence Data ◽  
Haplotype Network ◽  
Ovis Aries ◽  
Similar Species ◽  
Nucleotide Polymorphisms ◽  
Mt Dna ◽  
Protein Coding ◽  
Sister Clade ◽  
Mtdna Sequence ◽  
The Impact

Abstract Domestic yak (Bos grunniens) are bovids native to the Asian Qinghai-Tibetan Plateau. Studies of Asian yak have revealed that introgression with domestic cattle has contributed to the evolution of the species. When imported to North America (NA), some hybridization with B. taurus did occur. The objective of this study was to use mitochondrial (mt) DNA sequence data to better understand the mtDNA origin of NA yak and their relationship to Asian yak and related species. The complete mtDNA sequence of 14 individuals (12 NA yak, 1 Tibetan yak, 1 Tibetan B. indicus) was generated and compared with sequences of similar species from GeneBank (B. indicus, B. grunniens (Chinese), B. taurus, B. gaurus, B. primigenius, B. frontalis, Bison bison, and Ovis aries). Individuals were aligned to the B. grunniens reference genome (ARS_UNL_BGru_maternal_1.0), which was also included in the analyses. The mtDNA genes were annotated using the ARS-UCD1.2 cattle sequence as a reference. Ten unique NA yak haplotypes were identified, which a haplotype network separated into two clusters. Variation among the NA haplotypes included 93 nonsynonymous single nucleotide polymorphisms. A maximum likelihood tree including all taxa was made using IQtree after the data were partitioned into twenty-two subgroups using PartitionFinder2. Notably, six NA yak haplotypes formed a clade with B. indicus; the other four haplotypes grouped with B. grunniens and fell as a sister clade to bison, gaur and gayal. These data demonstrate two mitochondrial origins of NA yak with genetic variation in protein coding genes. Although these data suggest yak introgression with B. indicus, it appears to date prior to importation into NA. In addition to contributing to our understanding of the species history, these results suggest the two major mtDNA haplotypes in NA yak may functionally differ. Characterization of the impact of these differences on cellular function is currently underway.

scholarly journals Association of Genetic Polymorphisms in Oxidative Stress and Inflammation Pathways with Glaucoma Risk and Phenotype

2021 ◽  
Vol 10 (5) ◽  
pp. 1148
Author(s):  
Makedonka Atanasovska Velkovska ◽  
Katja Goričar ◽  
Tanja Blagus ◽  
Vita Dolžan ◽  
Barbara Cvenkel
Keyword(s):  
Oxidative Stress ◽  
Ocular Hypertension ◽  
Gene Deletion ◽  
Open Angle Glaucoma ◽  
Protective Role ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Gstm1 Gene ◽  
Stress Genes ◽  
The Impact

Oxidative stress and neuroinflammation are involved in the pathogenesis and progression of glaucoma. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in inflammation and oxidative stress genes on the risk of glaucoma, the patients’ clinical characteristics and the glaucoma phenotype. In total, 307 patients with primary open-angle glaucoma or ocular hypertension were enrolled. The control group included 339 healthy Slovenian blood donors. DNA was isolated from peripheral blood. Genotyping was performed for SOD2 rs4880, CAT rs1001179, GPX1 rs1050450, GSTP1 rs1695, GSTM1 gene deletion, GSTT1 gene deletion, IL1B rs1143623, IL1B rs16944, IL6 rs1800795 and TNF rs1800629. We found a nominally significant association of GSTM1 gene deletion with decreased risk of ocular hypertension and a protective role of IL1B rs16944 and IL6 rs1800629 in the risk of glaucoma. The CT and TT genotypes of GPX1 rs1050450 were significantly associated with advanced disease, lower intraocular pressure and a larger vertical cup–disc ratio. In conclusion, genetic variability in IL1B and IL6 may be associated with glaucoma risk, while GPX and TNF may be associated with the glaucoma phenotype. In the future, improved knowledge of these pathways has the potential for new strategies and personalised treatment of glaucoma.

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