Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic lupus erythematosus (SLE) is the prototype of complex autoimmune diseases. Studies have suggested that genetic, hormonal, and environmental factors contribute to the development of the disease. Interestingly, several recent studies involving SLE patients and mouse models of the disease have suggested a role for interferon (IFN)-stimulated genes (ISGs) in the development of SLE. One family of ISGs is the Ifi200-family, which includes mouse (Ifi202a, Ifi202b, Ifi203, Ifi204, and Ifi205) and human (IFI16, MNDA, AIM2, and IFIX) genes. The mouse genes cluster between serum amyloid P-component (Apcs) and alpha-spectrin (Spna-1) genes on chromosome 1 and the human genes cluster in syntenic region 1q23. The Ifi200-family genes encode structurally and functionally related proteins (the p200-family proteins). Increased expression of certain p200-family proteins in cells is associated with inhibition of cell proliferation, modulation of apoptosis, and cell differentiation. Our studies involving generation of B6.Nba2 congenic mice, coupled with gene expression analyses, identified the Ifi202 as a candidate lupus-susceptibility gene. Importantly, recent studies using different mouse models of SLE have suggested that increased expression of Ifi202 gene (encoding p202 protein) in immune cells contributes to lupus susceptibility. Consistent with a functional role for the p202 protein in lupus susceptibility, increased levels of IFI16 protein in human SLE patients are associated with the diseases. This review summarizes recent findings concerning the regulation and role of p200-family proteins in the development of SLE.
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PMID:Interferon-inducible Ifi200-family genes in systemic lupus erythematosus. 1859 17

The human HIN-200 gene cluster and its mouse counterpart, the interferon inducible-200 (Ifi200) family, both on Chr 1, are associated with several diseases, including solid tumors and lupus. Our study was initiated to identify the modifier gene(s) encoded by the Pctm locus, in which mouse B-cell plasmacytomas induced by pristane are associated with heterozygosity of Chr 1 genes near the Ifi200 cluster. A screen for differentially expressed genes in granulomatous tissues induced by pristane in resistant and susceptible strains identified a new Ifi200 member whose expression was 1000-fold higher in the strain carrying the resistant allele of Pctm and was the most highly expressed Ifi200 gene. The gene, designated Mndal (for MNDA-like, myeloid nuclear differentiation antigen-like), was absent in the susceptible genome, as were genomic sequences upstream of Ifi203, the gene adjacent to Mndal. Ectopic expression of MNDAL suppressed cell growth, which, together with the disease susceptibility of heterozygotes at the Pctm locus, suggests that Mndal, perhaps with Ifi203, acts as a tumor suppressor and display(s) haploinsufficiency. Mndal is highly polymorphic among inbred mouse strains, because it is absent in 10 of 24 strains. This polymorphism may have implications for other disease modifiers mapping to the same region.
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PMID:Mndal, a new interferon-inducible family member, is highly polymorphic, suppresses cell growth, and may modify plasmacytoma susceptibility. 1965 12

HIN200 is a human IFN-inducible gene and homologous to murine IFI202 gene, which was identified as a candidate gene for SLE susceptibility in lupus mouse model. We determined these gene expressions in leukocytes from 20 SLE patients and 10 healthy controls and in renal biopsies from 29 SLE patients and 15 kidney donors using sensitive real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The expressions of MNDA, IFIX, IFI16 and AIM2 genes significantly increased in leukocytes but not in kidney biopsies from SLE patients as compared to the control individuals, with P = 0.0003, P = 0.0056, P = 0.0002 and P < 0.0001, respectively. We also assessed the expression profiles of IFIX and IFI16 isoforms using semi-quantitative RT-PCR. We found up-regulation of B isoform (short product) of IFI16 in SLE patients. In addition, the expression levels were analyzed in correlation with disease activity and clinical characteristics. Interestingly, higher expression of MNDA was observed in patients who were positive for anti-dsDNA antibodies than in patients who were negative (P = 0.0276). In conclusion, it is suggested that the HIN200 genes have a role in SLE pathogenesis. Our study also observed a possible important role of a specific short isoform of IFI16 as well as a link between MNDA and anti-dsDNA antibody production.
Lupus 2009 Oct
PMID:Expression profile of HIN200 in leukocytes and renal biopsy of SLE patients by real-time RT-PCR. 1976 80

Deregulated innate immune responses that result in increased levels of type I interferons (IFNs) and stimulation of IFN-inducible genes are thought to contribute to chronic inflammation and autoimmunity. One family of IFN-inducible genes is the Ifi200 family, which includes the murine (eg, Ifi202a, Ifi202b, Ifi203, Ifi204, Mndal, and Aim2) and human (eg, IFI16, MNDA, IFIX, and AIM2) genes. Genes in the family encode structurally related proteins (the p200-family proteins), which share at least one partially conserved repeat of 200-amino acid (200-AA) residues. Consistent with the presence of 2 consecutive oligonucleotide/oligosaccharide-binding folds in the repeat, the p200-family proteins can bind to DNA. Additionally, these proteins (except the p202 proteins) also contain a pyrin (PYD) domain in the N-terminus. Increased expression of p202 proteins in certain strains of female mice is associated with lupus-like disease. Interestingly, only the Aim2 protein is conserved between the mouse and humans. Several recent studies have provided evidence that the Aim2 and p202 proteins can recognize DNA in cytoplasm and the Aim2 protein upon sensing DNA can form a caspase-1-activating inflammasome. In this review, we discuss how the ability of p200-family proteins to sense cytoplasmic DNA may contribute to the development of chronic inflammation and associated diseases.
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PMID:Interferon-inducible p200-family proteins as novel sensors of cytoplasmic DNA: role in inflammation and autoimmunity. 2018 76