| HLA DRB1*1503 allelic haplotype predominance and associated immunodysregulation in systemic lupus erythematosus. | |
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MedLine Citation:
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PMID: 21497601 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Systemic lupus erythematosus (SLE) is a chronic, relapsing, and remitting disease affecting primarily African American females of child bearing age. Familial aggregation of this disease suggests that at least part of the susceptibility for this disease is genetic, although environmental and hormonal influences are also likely to play a role. Early studies of genetic susceptibility to SLE revealed several of the major histocompatibility complex molecules, namely HLA DR, to be linked to SLE. Meta-analysis of genome scans has yielded loci significant for lupus patients, one of which includes the MHC region. Regulatory T cells are immunoregulatory cells that modulate activated immune cells. These cells play a large role in homeostasis of the immune responses and maintenance of immunologic tolerance, i.e., prevention of autoimmunity. Decreased numbers of regulatory T cells have been described in many autoimmune diseases, including systemic lupus erythematosus. Autoantibody production in systemic lupus erythematosus and the resulting immune complex formation and complex deposition into tissues are arguably the central core of immune dysregulation leading to disease manifestations and symptoms. Inability of the immune system to recognize and inhibit autoreactive immune cells in this particular autoimmune disease may be the result of inappropriate numbers and function of regulatory T cells. This study aims to characterize the immune cell population in patients from our community suffering from systemic lupus erythematosus and to prove that these patients exhibit a unique cellular profile compared to healthy age, race and gender matched control subjects. Surprisingly, our findings demonstrate that patients from the local Mississippi area exhibit increased proportions of CD25(+) FoxP3(+) regulatory T cells and CD25(+) FoxP3(-) T cells (of CD45(+) CD3(+) CD4(+) helper T cells) as compared to healthy controls. HLA tissue-typing of these lupus patients revealed a prominent subgroup (~30%) of patients possessing the HLA DRB1*1503 allele. The investigation of this subgroup demonstrated regulatory T cell composition similar to that of the total lupus group and to that of the non-HLA DRB1*1503 subgroup. Genetic analysis for molecular gene expression levels of various lupus-associated genes by real-time PCR demonstrated a unique profile as compared to healthy controls. Increased gene expression of FoxP3 together with decreased gene expression levels of GATA3, TNFAIP3, and TNFSF4 suggest that variations in gene products compared to healthy controls may be playing a role in the immune cell dysregulation and disproportionate CD25(+) FoxP3(+) regulatory T cells. |
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Authors:
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M Jeanann L Suggs; Vikas Majithia; Robert E Lewis; Julius M Cruse |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-04-08 |
Journal Detail:
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Title: Experimental and molecular pathology Volume: 91 ISSN: 1096-0945 ISO Abbreviation: Exp. Mol. Pathol. Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-03 Completed Date: 2011-11-22 Revised Date: 2012-01-31 |
Medline Journal Info:
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Nlm Unique ID: 0370711 Medline TA: Exp Mol Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 548-62 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Immunopathology, University of Mississippi Medical Center, 2500 North State St., Jackson, MS 39216, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult African Americans / genetics Alleles* Analysis of Variance Case-Control Studies Female Flow Cytometry Gene Expression Regulation Gene Frequency / genetics Genes, Dominant / genetics* Genetic Predisposition to Disease* HLA-DRB1 Chains / genetics* Haplotypes / genetics* Humans Lupus Erythematosus, Systemic / genetics*, immunology* Male Middle Aged RNA / standards T-Lymphocytes, Regulatory / immunology Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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RR 016476/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/HLA-DRB1 Chains; 63231-63-0/RNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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