The Autoimmune Ecology

Anaya, Juan Manuel; Ramírez-Santana, Carolina; Alzate, Maria A.; Molano-González, Nicolas; Rojas-Villarraga, Adriana

doi:10.3389/fimmu.2016.00139

Cited by 85 publications

(58 citation statements)

References 261 publications

(313 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Aims to match drug target genes with disease-associated genes obtained from genetic studies. For example, the development of a monoclonal antibody inhibitor to proprotein convertase subtilizing/kexin 9 (PCSK9) following detection of a gain-of-function mutation in the gene encoding the protein in families with hypercholesterolaemia [5]. An example earlier in development is that of interferon (IFN)-a blockers, which have been developed to treat systemic lupus erythematosus (SLE), partly on the basis of genetic evidence implicating IFN signalling pathways in the aetiology [6]; a recent clinical trial has reported promising results for anifrolumab in moderate-to-severe lupus [7].…”

Section: Profile-basedmentioning

confidence: 99%

Genetics of immune-mediated inflammatory diseases

David

Ling

Barton

2018

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Summary Immune‐mediated inflammatory diseases (IMIDs) are characterized by dysregulation of the normal immune response, which leads to inflammation. Together, they account for a high disease burden in the population, given that they are usually chronic conditions with associated co‐morbidities. Examples include systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease and type 1 diabetes. Since the advent of genome‐wide association studies, evidence of considerable genetic overlap in the loci predisposing to a wide range of IMIDs has emerged. Understanding the genetic risk and extent of genetic overlap between IMIDs may help to determine which genes control which aspects of the different diseases; it may identify potential novel therapeutic targets for a number of these conditions, and/or it may facilitate repurposing existing therapies developed originally for different conditions. The findings show that autoantibody‐mediated autoimmune diseases cluster more closely with each other than autoantibody‐negative diseases such as psoriasis, psoriatic arthritis, Crohn's disease and ankylosing spondylitis which, instead, form a seronegative genetic cluster. The genetic clustering largely mirrors the known response to existing biological therapies, but apparent anomalies in treatment response are discussed.

show abstract

Section: Profile-basedmentioning

confidence: 99%

Genetics of immune-mediated inflammatory diseases

David

Ling

Barton

2018

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…Anaya et al . ). The human as Homo microbis is an unstable and nonlinear accumulation, marked by disease tipping points with differing degrees of reversibility.…”

Section: Geography Dysbiosis and Global Healthmentioning

confidence: 97%

Parasites, ghosts and mutualists: a relational geography of microbes for global health

Lorimer

2017

Trans Inst British Geog

View full text Add to dashboard Cite

Scientific research on the microbiome offers an ecological model of the human, comprised of myriad forms of microbial life. The composition and dynamics of this human microbiome are increasingly implicated in discussions of health. Attention has focused on missing microbes and their links to a range of inflammatory and autoimmune diseases. Pathological dysbiosis is understood to result from both the excessive presence and the absence of microbes. Microbial declines have been indexed to modern hygiene and healthcare practices and there is a growing interest in the therapeutic use of beneficial microbes. This reappraisal of the salutary potential of microbes challenges the negative associations prevalent in health geography and the field of global health. This paper develops relational and multispecies approaches to health geography to examine situations of microbial excess, absence and controlled reintroduction. The analysis focuses on human relations with hookworms. Hookworms are animal members of the microbiome. They co-evolved with humans, live in us and are understood to manage the human microbiome to enable immunological tolerance. Both the excessive presence and the absence of hookworms can be pathological. They are currently the subjects of concurrent, but spatially discrete, programmes to deworm and reworm a variegated world. Focusing on this seeming spatial paradox, the analysis examines three types of human-hookworm relation: the parasite, the ghost and the mutualist. The conclusion reflects on the implications of this analysis for the human and nonhuman subjects of global health and the microbiopolitics of prevalent forms of antibiotic and probiotic healthcare.

show abstract

“…Thus, a "less is more" hypothesis could result in a limited repertoire response system towards external exposures but could be advantageous to promote stable and balanced autoimmune phenomena. The idea of the environment/exposure defining and driving a disease outcome is well accepted in autoimmunity (i.e., Autoimmune ecology) and it is starting to get the needed attention [43].…”

Section: Markermentioning

confidence: 99%

Homozygosity Analysis in Autoimmunity Affected Individuals and Multiplex Autoimmune Disease Families

Castiblanco¹,

Anaya²

2017

Immunome Res

View full text Add to dashboard Cite

Autoimmune diseases (AD) are responsible for a substantial amount of disability and morbidity worldwide. Research generally focuses on a single disease, although autoimmune phenotypes could represent pleiotropic outcomes of non-specific disease genes underlying similar immunogenetic mechanisms. This report examined the effect and importance of the homozygosity status, using genome-wide interspersed markers, in individuals and multiplex families affected with AD. This study presented two approaches: (I) a case-control comparison and evaluation on the effect of homozygosity at the genome-wide level and per marker, including 453 unrelated individuals (121 late-, 79 early-onset AD, 40 polyautoimmunity (PolyA), 30 multiple autoimmune syndrome (MAS) and 183 healthy control individuals); and (II) a model-free affected pair linkage approach which included 35 MAS, 49 polyA, 104 late-, and 83 early-onset multiplex families. A total of 372 genome-wide markers were used in the analysis. The standardized observed homozygosity (S OH ) was calculated and the association of the homozygosity status and the autoimmune trait was evaluated. The multipoint model-free linkage analysis was applied by using RELPAL from S.A.G.E v6.3. Results for the S OH showed significant differences between controls and early-onset individuals, where early-onset affected individuals showed lower homozygosity relative to controls. No differences were observed relative to controls for MAS, polyA and late-onset disease at the genome-wide level. The local marker homozygosity effect showed share and specific risk and/or protective effects for 24 markers. The model-free affected pair linkage approach lacked any suggestive linkage signals, but marginal signals displayed excess allele sharing for extreme phenotypes in autoimmunity. This study presumed autoimmunity as a trait rather than a clinical phenotype and tried to approach AD as a continuous trait presenting extreme phenotypes. Future approaches would be expected to dwell on the data presented here to corroborate and expand on sample size, marker coverage and their effects.

show abstract

The Autoimmune Ecology

Cited by 85 publications

References 261 publications

Genetics of immune-mediated inflammatory diseases

Genetics of immune-mediated inflammatory diseases

Parasites, ghosts and mutualists: a relational geography of microbes for global health

Homozygosity Analysis in Autoimmunity Affected Individuals and Multiplex Autoimmune Disease Families

Contact Info

Product

Resources

About