Autoimmune Diseases ; diagnosis ; genetics ; therapy ; Humans ; Liver Diseases ; diagnosis ; genetics ; therapy

Autoimmune-related skin diseases are a group of disorders with diverse etiology and pathophysiology involved in autoimmunity. Genetics and environmental factors may contribute to the development of these autoimmune disorders. Although the etiology and pathogenesis of these disorders are poorly understood, environmental variables that induce aberrant epigenetic regulations may provide some insights. Epigenetics is the study of heritable mechanisms that regulate gene expression without changing DNA sequences. The most important epigenetic mechanisms are DNA methylation, histone modification, and noncoding RNAs. In this review, we discuss the most recent findings regarding the function of epigenetic mechanisms in autoimmune-related skin disorders, including systemic lupus erythematosus, bullous skin diseases, psoriasis, and systemic sclerosis. These findings will expand our understanding and highlight the possible clinical applications of precision epigenetics approaches.
Humans ; Autoimmune Diseases/genetics* ; Epigenesis, Genetic ; Lupus Erythematosus, Systemic/genetics* ; DNA Methylation ; Psoriasis/genetics*

Autoimmune Diseases ; immunology ; Gene Expression Regulation ; immunology ; Humans ; Immunoglobulin G ; genetics ; immunology ; Sclerosis ; genetics ; immunology ; pathology

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Aicardi-Goutières syndrome 3 (AGS3). METHODS: Trio whole exome sequencing was carried out for the child and his parents, and candidate variants were verified by Sanger sequencing. To further clarify their pathogenicity, the crystal structure of the variants was simulated and analyzed, and the plasmid of variants was expressed in vitro. A literature search was also carried out to summarize the phenotypic and genetic characteristics of AGS3. RESULTS: The child was found to harbor novel compound heterozygous variants of the RNASEH2C gene, namely c.434G>T (p.Arg145Leu) and c.494G>C (p.Ter165Ser), which were inherited from his mother and father, respectively. Analysis of protein crystal structure suggested that the c.434G>T (p.Arg145Leu) variant may affect the stability of local structure, and in vitro experiments showed that this variant can lead to protein degradation. The c.494G>C (p.Ter165Ser) variant has destroyed the stop codon, resulting in prolonged variant. CONCLUSION The novel compound heterozygous variants of the RNASEH2C gene probably underlay the AGS3 in this child, which has enriched the phenotypic and mutational spectrum of this disorder.
Humans ; Child ; Mutation ; Autoimmune Diseases of the Nervous System/genetics* ; Nervous System Malformations/genetics*

The "Lübeck disaster", twins studies, adoptees studies, and other epidemiological observational studies have shown that host genetic factors play a significant role in determining the host susceptibility to Mycobacterium tuberculosis infection and pathogenesis of tuberculosis. From linkage analyses to genome-wide association studies, it has been discovered that human leucocyte antigen (HLA) genes as well as non-HLA genes (such as SLC11A1, VDR, ASAP1 as well as genes encoding cytokines and pattern recognition receptors) are associated with tuberculosis susceptibility. To provide ideas for subsequent studies about risk prediction of MTB infection and the diagnosis and treatment of tuberculosis, we review the research progress on tuberculosis susceptibility related genes in recent years, focusing on the correlation of HLA genes and non-HLA genes with the pathogenesis of tuberculosis. We also report the results of an enrichment analysis of the genes mentioned in the article. Most of these genes appear to be involved in the regulation of immune system and inflammation， and are also closely related to autoimmune diseases.
Humans ; Genome-Wide Association Study ; Tuberculosis/genetics* ; Gene Expression Regulation ; Cytokines/genetics* ; Autoimmune Diseases ; Mycobacterium tuberculosis/genetics* ; Genetic Predisposition to Disease

Autoimmune diseases (ADs) arise from an abnormal immune response of the body against substances and tissues normally present in the body. More than a hundred of ADs have been described in the literature so far. Although their etiology remains largely unclear, various types of ADs tend to share more associated genes with other types of ADs than with non-AD types. Here we present GAAD, a gene and AD association database. In GAAD, we collected 44,762 associations between 49 ADs and 4249 genes from public databases and MEDLINE documents. We manually verified the associations to ensure the quality and credibility. We reconstructed and recapitulated the relationships among ADs using their shared genes, which further validated the quality of our data. We also provided a list of significantly co-occurring gene pairs among ADs; with embedded tools, users can query gene co-occurrences and construct customized co-occurrence network with genes of interest. To make GAAD more straightforward to experimental biologists and medical scientists, we extracted additional information describing the associations through text mining, including the putative diagnostic value of the associations, type and position of gene polymorphisms, expression changes of implicated genes, as well as the phenotypical consequences, and grouped the associations accordingly. GAAD is freely available at http://gaad.medgenius.info.
Autoimmune Diseases ; genetics ; Data Mining ; Databases, Factual ; Gene Regulatory Networks ; Genetic Association Studies ; Humans

FcγRIIB, the only inhibitory IgG Fc receptor, functions to suppress the hyper-activation of immune cells. Numerous studies have illustrated its inhibitory function through the ITIM motif in the cytoplasmic tail of FcγRIIB. However, later studies revealed that in addition to the ITIM, the transmembrane (TM) domain of FcγRIIB is also indispensable for its inhibitory function. Indeed, recent epidemiological studies revealed that a non-synonymous single nucleotide polymorphism (rs1050501) within the TM domain of FcγRIIB, responsible for the I232T substitution, is associated with the susceptibility to systemic lupus erythematosus (SLE). In this review, we will summarize these epidemiological and functional studies of FcγRIIB-I232T in the past few years, and will further discuss the mechanisms accounting for the functional loss of FcγRIIB-I232T. Our review will help the reader gain a deeper understanding of the importance of the TM domain in mediating the inhibitory function of FcγRIIB and may provide insights to a new therapeutic target for the associated diseases.
Autoimmune Diseases ; drug therapy ; genetics ; immunology ; Humans ; Protein Domains ; Receptors, IgG ; chemistry ; immunology

Autoimmune diseases (AID) are a group of complex disorders due to antibodies acting on self-antigens causing damage to the body. AID has long been considered as the outcome of genetic and environmental interactions. In recent years, studies have shown that increased susceptibility to AID may be associated with single nucleotide polymorphisms and copy number variations of Toll like receptor 7 (TLR7) gene, which provided a clue to further understanding of the pathogenesis of AID. This paper provides a review of the recent advances in understanding of the roles of TLR7 gene single nucleotide polymorphisms and copy number variations in AID.
Animals ; Autoimmune Diseases ; genetics ; DNA Copy Number Variations ; Genetic Predisposition to Disease ; Humans ; Polymorphism, Single Nucleotide ; Toll-Like Receptor 7 ; genetics

OBJECTIVETo identify the A3243G mutation of mitochondrial (mt) DNA in patients with latent autoimmune diabetes mellitus in adults (LADA) of Han nationality in the northeast area of China.

METHODSSeventy-nine diabetics of Han nationality, whose families have resided in the northeast area of China for more than 3 generations, were divided into 3 groups: Group 1 (22 cases of type 2 diabetes with maternal inheritance history), Group 2 (34 cases of LADA), Group 3 (23 cases of type 1 diabetes in adolescents). The A3243G of mt DNA was detected in these 79 subjects with the method of PCR-RFLP.

RESULTSNone of the 79 diabetics studied was positively identified for the A3243G mutation of mt DNA.

CONCLUSIONThe A3243G mutation of mt DNA might not be related to the onset of LADA in diabetic population of Han nationality in northeast area of China and there might not be close relationship between A3243G mutation of mt DNA and autoimmunity.

Adolescent ; Adult ; Autoimmune Diseases ; genetics ; DNA, Mitochondrial ; genetics ; Diabetes Mellitus, Type 1 ; genetics ; Diabetes Mellitus, Type 2 ; genetics ; Female ; Humans ; Male ; Middle Aged ; Point Mutation

Sjögren's syndrome is a kind of autoimmune disease, whose main clinical symptoms are dry mouth, dry eye and chronic parotid glandular inflammation. The conservative treatments include artificial tears or saliva,oral administration of corticosteroids,and immunosuppressantsl with limited effectiveness. Along with the development of molecular biology, vast attentions are being paid to researches on gene therapy for Sjögren's syndrome, hopefully to bring gospel to patients with Sjögren's syndrome. This article reviews the recent research progresses on transcatheter delivery of recombinant adenovirus vector with aquaporin gene in experimental treatment of Sjögren's syndrome.
Adenoviridae ; Aquaporins ; genetics ; Autoimmune Diseases ; therapy ; Catheters ; Genetic Therapy ; Genetic Vectors ; administration & dosage ; Humans ; Sjogren's Syndrome ; therapy