scholarly journals Role of Interleukin- (IL-) 17 in the Pathogenesis and Targeted Therapies in Spondyloarthropathies

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
I-Tsu Chyuan ◽  
Ji-Yih Chen
Keyword(s):  
Animal Studies ◽  
Association Studies ◽  
Critical Role ◽  
Genetic Association Studies ◽  
Joint Inflammation ◽  
New Bone Formation ◽  
Unique Type ◽  
Targeting Therapy ◽  
Bone Damage

Spondyloarthropathy (SpA) is a unique type of joint inflammation characterized by coexisting erosive bone damage and pathological new bone formation. Previous genetic association studies have demonstrated that several cytokine pathways play a critical role in the pathogenesis of ankylosing spondylitis (AS), psoriatic arthritis (PsA), and other types of SpA. In addition to several well-known proinflammatory cytokines, recent studies suggest that IL-17 plays a pivotal role in the pathogenesis of SpA. Further evidence from human and animal studies have defined that IL-17 and IL-17-producing cells contribute to tissue inflammation, autoimmunity, and host defense, leading to the following pathologic events associated with SpA. Recently, several clinical trials targeting IL-17 pathways demonstrated the positive response of IL-17 blockade in treating AS, indicating a great potential of IL-17-targeting therapy in SpA. In this review article, we have discussed the contributing role of IL-17 and different IL-17-producing cells in the pathogenesis of SpA and provided an outline of therapeutic application of the IL-17 blockade in the treatment of SpA. Other targeted cytokines associated with IL-17 axis in SpA will also be included.

scholarly journals The Role of SNP Interactions when Determining Independence of Novel Signals in Genetic Association Studies—An Application to ARG1 and Bronchodilator Response

2021 ◽  
Vol 11 (2) ◽  
pp. 145
Author(s):  
Ryan Walsh ◽  
Kirsten Voorhies ◽  
Merry-Lynn McDonald ◽  
Michael McGeachie ◽  
Joanne E. Sordillo ◽  
...  
Keyword(s):  
Genetic Association ◽  
Association Studies ◽  
Critical Role ◽  
Genetic Association Studies ◽  
Genome Wide Association Studies ◽  
The Novel ◽  
Simulation Studies ◽  
Nucleotide Polymorphisms ◽  
Bronchodilator Response

Genome-wide association studies (GWAS) play a critical role in identifying many loci for common diseases and traits. There has been a rapid increase in the number of GWAS over the past decade. As additional GWAS are being conducted, it is unclear whether a novel signal associated with the trait of interest is independent of single nucleotide polymorphisms (SNPs) in the same region that has been previously associated with the trait of interest. The general approach to determining whether the novel association is independent of previous signals is to examine the association of the novel SNP with the trait of interest conditional on the previously identified SNP and/or calculate linkage disequilibrium (LD) between the two SNPs. However, the role of epistasis and SNP by SNP interactions are rarely considered. Through simulation studies, we examined the role of SNP by SNP interactions when determining the independence of two genetic association signals. We have created an R package on Github called gxgRC to generate these simulation studies based on user input. In genetic association studies of asthma, we considered the role of SNP by SNP interactions when determining independence of signals for SNPs in the ARG1 gene and bronchodilator response.

scholarly journals The State of the Art and Prospects for Osteoimmunomodulatory Biomaterials

Materials ◽  
2021 ◽  
Vol 14 (6) ◽  
pp. 1357
Author(s):  
Andreea-Mariana Negrescu ◽  
Anisoara Cimpean
Keyword(s):  
Foreign Bodies ◽  
Structural Characteristics ◽  
Critical Role ◽  
Fibrous Tissue ◽  
Bioactive Molecules ◽  
New Bone Formation ◽  
Recent Developments

The critical role of the immune system in host defense against foreign bodies and pathogens has been long recognized. With the introduction of a new field of research called osteoimmunology, the crosstalk between the immune and bone-forming cells has been studied more thoroughly, leading to the conclusion that the two systems are intimately connected through various cytokines, signaling molecules, transcription factors and receptors. The host immune reaction triggered by biomaterial implantation determines the in vivo fate of the implant, either in new bone formation or in fibrous tissue encapsulation. The traditional biomaterial design consisted in fabricating inert biomaterials capable of stimulating osteogenesis; however, inconsistencies between the in vitro and in vivo results were reported. This led to a shift in the development of biomaterials towards implants with osteoimmunomodulatory properties. By endowing the orthopedic biomaterials with favorable osteoimmunomodulatory properties, a desired immune response can be triggered in order to obtain a proper bone regeneration process. In this context, various approaches, such as the modification of chemical/structural characteristics or the incorporation of bioactive molecules, have been employed in order to modulate the crosstalk with the immune cells. The current review provides an overview of recent developments in such applied strategies.

scholarly journals A systematic review and meta-analysis of genetic association studies for the role of inflammation and the immune system in diabetic nephropathy

2017 ◽  
Vol 10 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Maria Tziastoudi ◽  
Ioannis Stefanidis ◽  
Georgios M. Hadjigeorgiou ◽  
Konstantinos Stravodimos ◽  
Elias Zintzaras
Keyword(s):  
Systematic Review ◽  
Diabetic Nephropathy ◽  
Immune System ◽  
Genetic Association ◽  
Association Studies ◽  
Meta Analysis ◽  
Genetic Association Studies

scholarly journals Lack of Association betweenPRNPM129V Polymorphism and Multiple Sclerosis, Mild Cognitive Impairment, Alcoholism and Schizophrenia in a Korean Population

2010 ◽  
Vol 28 (5) ◽  
pp. 315-321 ◽  
Author(s):  
Ihn-Geun Choi ◽  
Sung-Il Woo ◽  
Ho Jin Kim ◽  
Dai-Jin Kim ◽  
Byung Lae Park ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Genetic Association ◽  
Prion Diseases ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Korean Population ◽  
Weak Influence

The genetic variant at codon 129 (M129V) of the prion protein gene (PRNP) is considered to be a major genetic risk factor for prion diseases. In this study, we examined the possible genetic association ofPRNP*129Valwith multiple sclerosis (MS,n= 681), mild cognitive impairment (MCI,n= 801), alcoholism (n= 761) and schizophrenia (n= 715) in a Korean population, and compared the data with previous genetic association studies of the variant. The minor allele frequency ofPRNP*129Val(MAF = 0.025) was significantly lower in Korean population (n= 2,479) compared to Caucasian populations (P< 0.0001), suggestive of a weak influence of the variant in the previous population. Statistical analysis revealed no significant association betweenPRNP*129Valand MS (P = 0.76), MCI (P = 0.46), alcoholism (P = 0.84) and schizophrenia (P = 0.69). These findings were discussed in the context of prior inconsistent reports on the role ofPRNP*129Valpolymorphism in several diseases. Results from this study may provide further evidence thatPRNP M129Vis not a genetic susceptibility factor for MS, MCI, alcoholism and schizophrenia in a Korean population.

scholarly journals Carotid Artery Atherosclerosis: A Review on Heritability and Genetics

2018 ◽  
Vol 21 (5) ◽  
pp. 333-346 ◽  
Author(s):  
Bianka Forgo ◽  
Emanuela Medda ◽  
Anita Hernyes ◽  
Laszlo Szalontai ◽  
David Laszlo Tarnoki ◽  
...  
Keyword(s):  
Association Studies ◽  
Genetic Association Studies ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Phenotypic Variance ◽  
Genome Wide Association Studies ◽  
Genetic Associations ◽  
Carotid Artery Atherosclerosis ◽  
Meta Analyses

Carotid atherosclerosis (CAS) is associated with increased cardiovascular risk, and therefore, assessing the genetic versus environmental background of CAS traits is of key importance. Carotid intima-media-thickness and plaque characteristics seem to be moderately heritable, with remarkable differences in both heritability and presence or severity of these traits among ethnicities. Although the considerable role of additive genetic effects is obvious, based on the results so far, there is an important emphasis on non-shared environmental factors as well. We aimed to collect and summarize the papers that investigate twin and family studies assessing the phenotypic variance attributable to genetic associations with CAS. Genes in relation to CAS markers were overviewed with a focus on genetic association studies and genome-wide association studies. Although the role of certain genes is confirmed by studies conducted on large populations and meta-analyses, many of them show conflicting results. A great focus should be on future studies elucidating the exact pathomechanism of these genes in CAS in order to imply them as novel therapeutic targets.

Human Fetal Hemoglobin Expression Is Regulated by the Developmental Stage-Specific Repressor BCL11A

Science ◽  
2008 ◽  
Vol 322 (5909) ◽  
pp. 1839-1842 ◽  
Author(s):  
Vijay G. Sankaran ◽  
Tobias F. Menne ◽  
Jian Xu ◽  
Thomas E. Akie ◽  
Guillaume Lettre ◽  
...  
Keyword(s):  
Association Studies ◽  
Globin Gene ◽  
Genetic Association Studies ◽  
Fetal Hemoglobin ◽  
Sequence Variants ◽  
Erythroid Cells ◽  
Cell Disease ◽  
Direct Role ◽  
Globin Gene Regulation

Differences in the amount of fetal hemoglobin (HbF) that persists into adulthood affect the severity of sickle cell disease and the β-thalassemia syndromes. Genetic association studies have identified sequence variants in the gene BCL11A that influence HbF levels. Here, we examine BCL11A as a potential regulator of HbF expression. The high-HbF BCL11A genotype is associated with reduced BCL11A expression. Moreover, abundant expression of full-length forms of BCL11A is developmentally restricted to adult erythroid cells. Down-regulation of BCL11A expression in primary adult erythroid cells leads to robust HbF expression. Consistent with a direct role of BCL11A in globin gene regulation, we find that BCL11A occupies several discrete sites in the β-globin gene cluster. BCL11A emerges as a therapeutic target for reactivation of HbF in β-hemoglobin disorders.

Mo1929 Critical Role of Chromogranin-A on Macrophage Intrinsic Apoptotic Pathway in Colitis: Human and Animal studies

2016 ◽  
Vol 150 (4) ◽  
pp. S819 ◽  
Author(s):  
Nour Eissa ◽  
Mohammad F. Rabbi ◽  
Peris M. Munyaka ◽  
Azin Khafipour ◽  
Charles N. Bernstein ◽  
...  
Keyword(s):  
Chromogranin A ◽  
Animal Studies ◽  
Critical Role ◽  
Intrinsic Apoptotic Pathway ◽  
Apoptotic Pathway

The critical role of kinase activity of interleukin-1 receptor-associated kinase 4 in animal models of joint inflammation

2009 ◽  
Vol 60 (6) ◽  
pp. 1661-1671 ◽  
Author(s):  
Magdalena Koziczak-Holbro ◽  
Amanda Littlewood-Evans ◽  
Bernadette Pöllinger ◽  
Jiri Kovarik ◽  
Janet Dawson ◽  
...  
Keyword(s):  
Animal Models ◽  
Kinase Activity ◽  
Interleukin 1 ◽  
Critical Role ◽  
Joint Inflammation

Lipoprotein-associated Phospholipase A2 and Coronary Heart Disease

2018 ◽  
Vol 24 (3) ◽  
pp. 291-296 ◽  
Author(s):  
Areti Sofogianni ◽  
Stelina Alkagiet ◽  
Konstantinos Tziomalos
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Phospholipase A2 ◽  
Therapeutic Target ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Markers Of Inflammation ◽  
Chd Risk ◽  
Increased Risk

In the last decades, the role of inflammation in the pathogenesis of atherosclerosis has been the topic of intense research. Several markers of inflammation have shown predictive value for first and recurrent coronary events in patients without and with established Coronary Heart Disease (CHD). Among these markers, lipoprotein- associated phospholipase A2 (Lp-PLA2) has recently received considerable attention. In the present review, the potential role of Lp-PLA2 as a marker of CHD risk and as a therapeutic target is discussed. Elevated Lp- PLA2 mass and activity appears to be associated with increased risk for CHD, both in the general population and in patients with established CHD. However, it is unclear whether the measurement of Lp-PLA2 improves risk discrimination when incorporated in models that include traditional cardiovascular risk factors. Moreover, the lack of effect on CHD events of darapladib, a potent, selective Lp-PLA2 inhibitor, in two large, randomized, placebo-controlled trials and the mostly negative findings of genetic association studies suggest that Lp-PLA2 is unlikely to represent a causal factor in atherogenesis. Therefore, it is doubtful whether Lp-PLA2 will constitute a therapeutic target for the prevention of CHD.

scholarly journals Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jean-Yves Dubé ◽  
Vinicius M. Fava ◽  
Erwin Schurr ◽  
Marcel A. Behr
Keyword(s):  
Pattern Recognition ◽  
Mycobacterium Tuberculosis ◽  
Association Studies ◽  
Scientific Evidence ◽  
Critical Role ◽  
Genetic Association Studies ◽  
Direct Interaction ◽  
Pattern Recognition Receptors ◽  
Disease Genes ◽  
Genes Encoding

Human genetic control is thought to affect a considerable part of the outcome of infection with Mycobacterium tuberculosis (Mtb). Most of us deal with the pathogen by containment (associated with clinical “latency”) or sterilization, but tragically millions each year do not. After decades of studies on host genetic susceptibility to Mtb infection, genetic variation has been discovered to play a role in tuberculous immunoreactivity and tuberculosis (TB) disease. Genes encoding pattern recognition receptors (PRRs) enable a consistent, molecularly direct interaction between humans and Mtb which suggests the potential for co-evolution. In this review, we explore the roles ascribed to PRRs during Mtb infection and ask whether such a longstanding and intimate interface between our immune system and this pathogen plays a critical role in determining the outcome of Mtb infection. The scientific evidence to date suggests that PRR variation is clearly implicated in altered immunity to Mtb but has a more subtle role in limiting the pathogen and pathogenesis. In contrast to ‘effectors’ like IFN-γ, IL-12, Nitric Oxide and TNF that are critical for Mtb control, ‘sensors’ like PRRs are less critical for the outcome of Mtb infection. This is potentially due to redundancy of the numerous PRRs in the innate arsenal, such that Mtb rarely goes unnoticed. Genetic association studies investigating PRRs during Mtb infection should therefore be designed to investigate endophenotypes of infection – such as immunological or clinical variation – rather than just TB disease, if we hope to understand the molecular interface between innate immunity and Mtb.

Sign in / Sign up

Export Citation Format

Share Document