Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-alpha and TNF-beta by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus

Details

Serval ID
serval:BIB_E6FBC18B7076
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-alpha and TNF-beta by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus
Journal
European Journal of Immunology
Author(s)
Pociot  F., Briant  L., Jongeneel  C. V., Molvig  J., Worsaae  H., Abbal  M., Thomsen  M., Nerup  J., Cambon-Thomsen  A.
ISSN
0014-2980 (Print)
Publication state
Published
Issued date
01/1993
Volume
23
Number
1
Pages
224-31
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan
Abstract
We have investigated the correlation between different tumor necrosis factor (TNF) and class II major histocompatibility complex alleles in the lipopolysaccharide- or phytohemagglutinin-induced secretion of TNF-alpha and TNF-beta by human monocytes and peripheral blood mononuclear cells in 87 unrelated Danish male individuals. Significant differences in TNF-alpha secretory capacity between TNF NcoI restriction fragment length polymorphisms, TNFa and TNFc microsatellite alleles and DR alleles were identified. No correlation with TNF-beta secretory capacity was found for any of the markers studied. TNF genotyping allowed us to define four extended HLA haplotypes which correlate with TNF-alpha secretory capacity. Two of these are DR4 positive: DQw8, DR4, TNFB*1, TNFa6, B44, A2 and DQw8, DR4, TNFB*2, TNFa2, B15, A2. Individuals carrying the TNFB*2, TNFa2 haplotype had a higher TNF-alpha secretory capacity than those carrying the TNFB*1, TNFa6 haplotype. In a group of DR3/DR4 heterozygous patients with insulin-dependent diabetes mellitus (IDDM), the frequency of the TNFa2 allele was higher than in HLA-DR matched controls, whereas the TNFa6 allele was more frequent in control individuals. In the DR3/DR4 heterozygous diabetic group 12/26 had the alleles combination DQw8, DR4 (Dw4), C4A3, TNFB*2, TNFa2, B15, whereas only 1/18 controls had this haplotype. This diabetogenic haplotype is identical to the DR4 haplotype which correlates with a higher TNF-alpha response. These observations suggest a direct role for the TNF locus in the pathogenesis of IDDM.
Keywords
Adolescent Adult *Alleles Diabetes Mellitus, Type 1/*genetics/metabolism *Genes, MHC Class II Genotype HLA-DR Antigens/*genetics Haplotypes Heterozygote Humans Leukocyte Count Linkage (Genetics) Lymphotoxin-alpha/*genetics/secretion Male Polymorphism, Restriction Fragment Length Tumor Necrosis Factor-alpha/*genetics/secretion
Pubmed
Web of science
Create date
24/01/2008 15:39
Last modification date
20/08/2019 16:10
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