scholarly journals Genetic Dissection of SLE

2002 ◽  
Vol 196 (3) ◽  
pp. 281-292 ◽  
Author(s):  
Xiaoyan Shi ◽  
Chun Xie ◽  
Desi Kreska ◽  
James A. Richardson ◽  
Chandra Mohan
Keyword(s):  
T Cells ◽  
Clinical Evidence ◽  
Gene Dosage ◽  
Recessive Gene ◽  
Genetic Dissection ◽  
Gene Dosage Effect ◽  
B1a Cells ◽  
Lupus Pathogenesis ◽  
Congenic Interval ◽  
Dna Antibodies

Genetic dissection of lupus pathogenesis in the NZM2410 strain has recently revealed that Sle1 is a potent locus that triggers the formation of IgG anti-histone/DNA antibodies, when expressed on the B6 background as a congenic interval. B6.lpr mice, in contrast, exhibit distinctly different cellular and serological phenotypes. Both strains, however, do not usually exhibit pathogenic autoantibodies, or succumb to lupus nephritis. In this study, we show that the epistatic interaction of Sle1 (in particular, Sle1/Sle1) with FASlpr leads to massive lymphosplenomegaly (with elevated numbers of activated CD4 T cells, CD4−CD8− double negative (DN) T cells, and B1a cells), high levels of IgG and IgM antinuclear (including anti-ssDNA, anti-dsDNA, and anti-histone/DNA), and antiglomerular autoantibodies, histological, and clinical evidence of glomerulonephritis, and >80% mortality by 5–6 mo of age. Whereas FASlpr functions as a recessive gene, Sle1 exhibits a gene dosage effect. These studies indicate that Sle1 and FASlpr must be impacting alternate pathways leading to lymphoproliferative autoimmunity.

scholarly journals Conditional Knockout of the RNA-Binding Protein HuR in CD4+ T Cells Reveals a Gene Dosage Effect on Cytokine Production

2014 ◽  
Vol 20 (1) ◽  
pp. 93-108 ◽  
Author(s):  
Matthew M. Gubin ◽  
Patsharaporn Techasintana ◽  
Joseph D. Magee ◽  
Garrett M. Dahm ◽  
Robert Calaluce ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Rna Binding ◽  
Cytokine Production ◽  
Gene Dosage ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Dosage Effect ◽  
Conditional Knockout ◽  
Gene Dosage Effect

Decreased Generation and Function of CD4+CD25hi T Regulatory Cells in Human STAT5b Deficiency.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 768-768
Author(s):  
Aileen Cleary ◽  
Kari Nadeau ◽  
Wenwei Tu ◽  
Vivian Hwa ◽  
Kira Y. Dionis ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Gene Dosage ◽  
Foxp3 Expression ◽  
Intermediate Phenotype ◽  
Gamma Chain ◽  
Gene Dosage Effect ◽  
And Function

Abstract CD4+ CD25+ regulatory T cells (Tregs) are a well characterized population of cells that play an important role in limiting inflammation and in the maintenance of tolerance to self. Here we describe a patient with a homozygous missense mutation (A630P) in the STAT5b gene who clinically displays immune dysregulation in association with decreased numbers and function of Tregs. Freshly isolated or in vitro-derived CD4+CD25high Treg cells from this patient had low Foxp3 expression, did not suppress non Treg T-cell proliferation, and were unable to kill autologous CD4+CD25neg T cells compared to controls. CD25 expression in response to IL-2 did not increase on freshly isolated CD4 T cells and was decreased on T-cell blasts derived from the patient. The patients mother who was heterozygous for this mutation had an intermediate phenotype for all of these immune abnormalities, indicating a gene dosage effect. In contrast, IL-2 upregulated expression of the common gamma chain (γc) cytokine receptor and perforin by T cells normally. Activation-induced T-cell expression of CD40-ligand (CD154) and interferon-gamma (IFN-γ) were also normal in the patient. These results suggest that the STAT5 pathway propagates an important IL-2 mediated signal that is necessary for Treg generation and function in humans in vivo.

Evidence of a gene-dosage effect for the glucocorticoid receptor in trisomy 18 mice

1987 ◽  
Vol 116 (3_Suppl) ◽  
pp. S95-S96
Author(s):  
D. VOGLIOLO ◽  
H. WINKING ◽  
R. KNUPPEN
Keyword(s):  
Glucocorticoid Receptor ◽  
Gene Dosage ◽  
Dosage Effect ◽  
Trisomy 18 ◽  
Gene Dosage Effect

Cancer Immunology and CAR-T Cells: A Turning Point Therapeutic Approach in Colorectal Carcinoma with clinical insight

2020 ◽  
Vol 20 ◽  
Author(s):  
Suman K Ray ◽  
Yamini Meshram ◽  
Sukhes Mukherjee
Keyword(s):  
T Cells ◽  
Colorectal Carcinoma ◽  
Cancer Immunotherapy ◽  
Clinical Evidence ◽  
Ex Vivo ◽  
Clinical Success ◽  
Recent Decade ◽  
Molecular Immunology ◽  
Car T ◽  
Engineered T Cells

: Cancer immunotherapy endeavours in harnessing delicate strength and specificity of immune system for therapy of different malignancies including colorectal carcinoma. The recent challenge for cancer immunotherapy is to practice and develop molecular immunology tools to create tactics that efficiently and securely boost antitumor reactions. After several attempts of deceptive outcomes, the wave has lastly altered and immunotherapy has become a clinically confirmed treatment for several cancers. Immunotherapeutic methods include administration of antibodies or modified proteins that either block cellular activity or co-stimulate cells through immune control pathways, cancer vaccines, oncolytic bacteria, ex vivo activated adoptive transfer of T cells and natural killer cells. Engineered T cells are used to produce a chimeric antigen receptor (CAR) to treat different malignancies including colorectal carcinoma in a recent decade. Despite considerable early clinical success, CAR-T therapies are associated with some side effects and sometimes display minimal efficacy. It gives special emphasis on the latest clinical evidence with CAR-T technology and also other related immunotherapeutic methods with promising performance, and highlighted how this therapy can affect therapeutic outcome and next upsurge as a key clinical aspect of colorectal carcinoma. In this review we recapitulate the current developments produced to improve the efficacy and specificity of CAR-T therapies in colon cancer.

Apparent Lack of Gene Dosage Effect in the PLT Assay

1977 ◽  
Vol 6 (5) ◽  
pp. 529-532 ◽  
Author(s):  
S. JARAMILLO ◽  
G. ANHORN ◽  
F. SCHUNTER ◽  
P. WERNET
Keyword(s):  
Gene Dosage ◽  
Dosage Effect ◽  
Gene Dosage Effect ◽  
Apparent Lack

Activation of autoreactive T cells that help nucleobindin-injected mice produce anti-DNA antibodies

2001 ◽  
Vol 75 (2) ◽  
pp. 111-115 ◽  
Author(s):  
Tetsuo Kubota ◽  
Naomi Watanabe ◽  
Takamasa Kaneko ◽  
Fumiaki Satake ◽  
Keiji Miura ◽  
...  
Keyword(s):  
T Cells ◽  
Autoreactive T Cells ◽  
Dna Antibodies

Gene dosage effect in expression of blood group antigens

1973 ◽  
Vol 83 (2) ◽  
pp. 167-172
Author(s):  
Li-Tsun Chen ◽  
Joseph A. Davidenas ◽  
Roal F. Ruth
Keyword(s):  
Blood Group ◽  
Gene Dosage ◽  
Dosage Effect ◽  
Blood Group Antigens ◽  
Gene Dosage Effect

scholarly journals The Impact of T Cell Vaccination in Alleviating and Regulating Systemic Lupus Erythematosus Manifestation

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Liuye Huang ◽  
Yuan Yang ◽  
Yu Kuang ◽  
Dapeng Wei ◽  
Wanyi Li ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Side Effects ◽  
Lupus Erythematosus ◽  
Clinical Symptoms ◽  
Systemic Lupus ◽  
T Cell Vaccination ◽  
Dna Antibodies

Objective. Systemic lupus erythematosus (SLE) is an autoimmune disease identified by a plethora of production of autoantibodies. Autoreactive T cells may play an important role in the process. Attenuated T cell vaccination (TCV) has proven to benefit some autoimmune diseases by deleting or suppressing pathogenic T cells. However, clinical evidence for TCV in SLE is still limited. Therefore, this self-controlled study concentrates on the clinical effects of TCV on SLE patients. Methods. 16 patients were enrolled in the study; they accepted TCV regularly. SLEDAI, clinical symptoms, blood parameters including complements 3 and 4 levels, ANA, and anti-ds-DNA antibodies were tested. In addition, the side effects and drug usage were observed during the patients’ treatment and follow-up. Results. Remissions in clinical symptoms such as facial rash, vasculitis, and proteinuria were noted in most patients. There are also evident reductions in SLEDAI, anti-ds-DNA antibodies, and GC dose and increases in C3 and C4 levels, with no pathogenic side effects during treatment and follow-up. Conclusions. T cell vaccination is helpful in alleviating and regulating systemic lupus erythematosus manifestation.

CYSTIC FIBROSIS OF THE PANCREAS

PEDIATRICS ◽  
1957 ◽  
Vol 19 (6) ◽  
pp. 1136-1138
Author(s):  
Paul A. di Sant'Agnese ◽  
Charles Upton Lowe
Keyword(s):  
Cystic Fibrosis ◽  
Clinical Evidence ◽  
Clinical Effect ◽  
Single Gene ◽  
Pancreatic Insufficiency ◽  
Recessive Gene ◽  
The United States ◽  
Live Births ◽  
Almost All ◽  
Very High

IN THE COURSE of a review of all features of the disease, the following points were particularly noteworthy: Incidence This disease accounts for almost all cases of pancreatic insufficiency in children. The incidence in the population of the United States is between 1 in 600 and 1 in 10,000 live births, with a probable average incidence of 1 in 2,500. There is no sex predominance. There is, however, a difference in racial predilection, being rarely seen in the Negro and never in Mongolians. It is a familial disease, displaying the characteristics of a mendelian recessive gene. This means that in an affected family the disease may occur in approximately 25% of the offspring, that both parents must be carriers of the trait and that two-thirds of the non-affected children are also carriers. Birth order has no effect on the inheritance of this disease. The fact that it is usually a lethal disease indicates that the mutation rate for this gene must be very high; the frequency of the single gene in the population has been calculated to be approximately 1 in 50. Pancreatic Insufficiency Clinical evidence of poor digestion and absorption of protein and fat is seen in the increased quantities of these substances in the feces, which causes the feces to be bulky, foul smelling, foamy and greasy. Another clinical effect of malabsorption is seen in the failure of the newborn infant with cystic fibrosis of the pancreas to regain birth weight in the first 10 days of life. In the absence of other evidence of disease, this is a sign suggestive of pancreatic failure.

scholarly journals THE GENETIC BASIS OF DOSAGE COMPENSATION OF ALCOHOL DEHYDROGENASE-1 IN MAIZE

Genetics ◽  
1981 ◽  
Vol 97 (3-4) ◽  
pp. 625-637 ◽  
Author(s):  
James A Birchler
Keyword(s):  
Alcohol Dehydrogenase ◽  
Structural Gene ◽  
Dosage Compensation ◽  
Genetic Basis ◽  
Gene Dosage ◽  
Dosage Effect ◽  
Gene Dosage Effect ◽  
Negative Effect ◽  
Higher Eukaryotes ◽  
Alcohol Dehydrogenase 1

ABSTRACT The levels of alcohol dehydrogenase (ADH) do not exhibit a structural gene-dosage effect in a one to four dosage series of the long arm of chromosome one (1L) (BIRCHLER19 79). This phenomenon, termed dosage compensation, has been studied in more detail. Experiments are described in which individuals aneuploid for shorter segments were examined for the level of ADH in order to characterize the genetic nature of the compensation. The relative ADH expression in segmental trisomics and tetrasomics of region IL 0.72–0.90, which includes the Adh locus, approaches the level expected from a strict gene dosage effect. Region IL 0.20–0.72 produces a negative effect upon ADH in a similar manner to that observed with other enzyme levels when IL as a whole is varied (BIRCHLEF1I9 79). These and other comparisons have led to the concept that the compensation of ADH results from the cancellation of the structural gene effect by the negative aneuploid effect. The example of ADH is discussed as a model for certain other cases of dosage compensation in higher eukaryotes.

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