Dataset Information

Advances in the Immunology and Genetics of Leprosy.

ABSTRACT: Leprosy, a disease caused by the intracellular parasite Mycobacterium leprae or Mycobacterium lepromatosis, has affected humans for more than 4,000 years and is a stigmatized disease even now. Since clinical manifestations of leprosy patients present as an immune-related spectrum, leprosy is regarded as an ideal model for studying the interaction between host immune response and infection; in fact, the landscape of leprosy immune responses has been extensively investigated. Meanwhile, leprosy is to some extent a genetic disease because the genetic factors of hosts have long been considered major contributors to this disease. Many immune-related genes have been discovered to be associated with leprosy. However, immunological and genetic findings have rarely been studied and discussed together, and as a result, the effects of gene variants on leprosy immune responses and the molecular mechanisms of leprosy pathogenesis are largely unknown. In this context, we summarized advances in both the immunology and genetics of leprosy and discussed the perspective of the combination of immunological and genetic approaches in studying the molecular mechanism of leprosy pathogenesis. In our opinion, the integrating of immunological and genetic approaches in the future may be promising to elucidate the molecular mechanism of leprosy onset and how leprosy develops into different types of leprosy.

SUBMITTER: Mi Z

PROVIDER: S-EPMC7176874 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Advances in the Immunology and Genetics of Leprosy.

Mi Zihao Z Liu Hong H Zhang Furen F

Frontiers in immunology 20200416

Leprosy, a disease caused by the intracellular parasite <i>Mycobacterium leprae</i> or <i>Mycobacterium lepromatosis</i>, has affected humans for more than 4,000 years and is a stigmatized disease even now. Since clinical manifestations of leprosy patients present as an immune-related spectrum, leprosy is regarded as an ideal model for studying the interaction between host immune response and infection; in fact, the landscape of leprosy immune responses has been extensively investigated. Meanwhi ...[more]

PMID: 32373110

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Project description:BACKGROUND:Migraine is a complex neurovascular disorder with a strong genetic component. There are rare monogenic forms of migraine, as well as more common polygenic forms; research into the genes involved in both types has provided insights into the many contributing genetic factors. This review summarises advances that have been made in the knowledge and understanding of the genes and genetic variations implicated in migraine etiology. FINDINGS:Migraine is characterised into two main types, migraine without aura (MO) and migraine with aura (MA). Hemiplegic migraine is a rare monogenic MA subtype caused by mutations in three main genes - CACNA1A, ATP1A2 and SCN1A - which encode ion channel and transport proteins. Functional studies in cellular and animal models show that, in general, mutations result in impaired glutamatergic neurotransmission and cortical hyperexcitability, which make the brain more susceptible to cortical spreading depression, a phenomenon thought to coincide with aura symptoms. Variants in other genes encoding ion channels and solute carriers, or with roles in regulating neurotransmitters at neuronal synapses, or in vascular function, can also cause monogenic migraine, hemiplegic migraine and related disorders with overlapping symptoms. Next-generation sequencing will accelerate the finding of new potentially causal variants and genes, with high-throughput bioinformatics analysis methods and functional analysis pipelines important in prioritising, confirming and understanding the mechanisms of disease-causing variants. With respect to common migraine forms, large genome-wide association studies (GWAS) have greatly expanded our knowledge of the genes involved, emphasizing the role of both neuronal and vascular pathways. Dissecting the genetic architecture of migraine leads to greater understanding of what underpins relationships between subtypes and comorbid disorders, and may have utility in diagnosis or tailoring treatments. Further work is required to identify causal polymorphisms and the mechanism of their effect, and studies of gene expression and epigenetic factors will help bridge the genetics with migraine pathophysiology. CONCLUSIONS:The complexity of migraine disorders is mirrored by their genetic complexity. A comprehensive knowledge of the genetic factors underpinning migraine will lead to improved understanding of molecular mechanisms and pathogenesis, to enable better diagnosis and treatments for migraine sufferers.

Dataset Information

Advances in the Immunology and Genetics of Leprosy.

Publications

Advances in the Immunology and Genetics of Leprosy.

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