Journal ArticleDOI
Genetic insights into common pathways and complex relationships among immune-mediated diseases.
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TLDR
It is revealed that several diseases share multiple susceptibility loci, but there are many nuances that help explain why early evidence of extensive 'sharing' is not always reflected in epidemiological overlap.Abstract:
Shared aetiopathogenic factors among immune-mediated diseases have long been suggested by their co-familiality and co-occurrence, and molecular support has been provided by analysis of human leukocyte antigen (HLA) haplotypes and genome-wide association studies. The interrelationships can now be better appreciated following the genotyping of large immune disease sample sets on a shared SNP array: the 'Immunochip'. Here, we systematically analyse loci shared among major immune-mediated diseases. This reveals that several diseases share multiple susceptibility loci, but there are many nuances. The most associated variant at a given locus frequently differs and, even when shared, the same allele often has opposite associations. Interestingly, risk alleles conferring the largest effect sizes are usually disease-specific. These factors help to explain why early evidence of extensive 'sharing' is not always reflected in epidemiological overlap.read more
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Elements of cancer immunity and the cancer–immune set point
Daniel S. Chen,Ira Mellman +1 more
TL;DR: Clinical studies are beginning to define these factors as immune profiles that can predict responses to immunotherapy, suggesting that a broader view of cancer immunity is required.
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Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases.
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Journal ArticleDOI
Genetic and Epigenetic Fine-Mapping of Causal Autoimmune Disease Variants
Kyle Kai-How Farh,Alexander Marson,Jiang Zhu,Markus Kleinewietfeld,William J. Housley,Samantha Beik,Noam Shoresh,Holly Whitton,Russell J.H. Ryan,Alexander A. Shishkin,Meital Hatan,Marlene J. Carrasco-Alfonso,Dita Mayer,C. John Luckey,Nikolaos A. Patsopoulos,Philip L. De Jager,Vijay K. Kuchroo,Charles B. Epstein,Mark J. Daly,David A. Hafler,Bradley E. Bernstein +20 more
TL;DR: A fine-mapping algorithm is developed to identify candidate causal variants for 21 autoimmune diseases from genotyping data, and it is found that most non-coding risk variants, including those that alter gene expression, affect non-canonical sequence determinants not well-explained by current gene regulatory models.
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The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy
TL;DR: A better understanding of how these variables cooperate to affect tumour–host interactions is needed to optimize the implementation of precision immunotherapy.
References
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Therapeutic benefit of blocking interleukin‐6 activity with an anti–interleukin‐6 receptor monoclonal antibody in rheumatoid arthritis: A randomized, double‐blind, placebo‐controlled, dose‐escalation trial
Ernest Choy,David A. Isenberg,Toby Garrood,S Farrow,Yiannis Ioannou,Howard A. Bird,Nap T. Cheung,Bryan D. Williams,B. L. Hazleman,R Price,Kazuyuki Yoshizaki,Norihiro Nishimoto,Tadamitsu Kishimoto,Gabriel S. Panayi +13 more
TL;DR: This is the first randomized controlled trial showing that inhibition of IL-6 significantly improved the signs and symptoms of RA and normalized the acute-phase reactants.
Journal ArticleDOI
The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases
Patricia Price,Campbell S. Witt,Richard J.N. Allcock,David Sayer,Michael J. Garlepp,C.C. Kok,Martyn A. French,Simon Mallal,Frank T. Christiansen +8 more
TL;DR: Several candidate genes in the central MHC have the potential to modulate immune or inflammatory responses in an antigen‐independent manner, as is seen in studies of cultured cells from healthy carriers of the 8.1 AH.
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