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Title: Analysis of DR4 haplotypes in insulin dependent diabetes (IDD)

Abstract

Population studies indicate that HLA-DR4 is implicated in the susceptibility of IDD. However, biochemical characterization of the serologically defined DR4 haplotype from normal individuals revealed five DR4 and three DQW3 molecular forms. Hence, in this study, they investigated the heterogeneity of the DR4 haplotype, using B-lymphoblastoid cell lines (B-LCL) generated from patients with IDD and seropositive for DR4. Class II molecules, metabolically labeled with /sup 35/S-methionine, were immunoprecipitated with monoclonal antibodies specific for DR(L243), DQ(N297), DQW3(IVD12) or DR and DQ(SG465) and analyzed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). The isoelectrofocusing (IEF) conditions employed in this study allow representation only of the DR4 haplotype from either DR3/4 or DR4/4 cell lines. The analysis of six different DR4 haplotypes from seven IDD patients, revealed the presence of two DR4 ..beta.. and two DQW3 ..beta.. chains. Three of the six DR4 ..beta.. haplotypes analyzed shared the same DR4 ..beta.. chain and three others shared a different one. Additionally five of the six haplotypes shared a different one. Additionally five of the six haplotypes shared the same DQW3 ..beta.. chain and only one was carrying a different one. Different combinations of the two DR4 and two DQW3 ..beta.. chains constitute three distinct patterns ofmore » DR4 haplotypes. These results suggest the prevalence of a DQW3 ..beta.. chain in the small sample of IDD patients studied. Studies of a large number of patients should clarify whether IDD is associated with unique variants of DR4 or DQW3 ..beta.. chains.« less

Authors:
; ; ;
Publication Date:
Research Org.:
Univ. of Pennsylvania, Philadelphia
OSTI Identifier:
6934836
Report Number(s):
CONF-8604222-
Journal ID: CODEN: FEPRA
Resource Type:
Conference
Journal Name:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
Additional Journal Information:
Journal Volume: 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ANIMAL CELLS; MOLECULAR STRUCTURE; DIABETES MELLITUS; PATHOGENESIS; ELECTROPHORESIS; HAPLOIDY; METHIONINE; MOLECULES; MONOCLONAL ANTIBODIES; PATIENTS; SULFUR 35; TRACER TECHNIQUES; AMINO ACIDS; ANTIBODIES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; CARBOXYLIC ACIDS; DAYS LIVING RADIOISOTOPES; DISEASES; DRUGS; ENDOCRINE DISEASES; EVEN-ODD NUCLEI; ISOTOPE APPLICATIONS; ISOTOPES; LIGHT NUCLEI; LIPOTROPIC FACTORS; METABOLIC DISEASES; NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC SULFUR COMPOUNDS; PLOIDY; RADIOISOTOPES; SULFUR ISOTOPES; 550901* - Pathology- Tracer Techniques

Citation Formats

Monos, D S, Radka, S F, Zmijewski, C M, and Kamoun, M. Analysis of DR4 haplotypes in insulin dependent diabetes (IDD). United States: N. p., 1986. Web.
Monos, D S, Radka, S F, Zmijewski, C M, & Kamoun, M. Analysis of DR4 haplotypes in insulin dependent diabetes (IDD). United States.
Monos, D S, Radka, S F, Zmijewski, C M, and Kamoun, M. 1986. "Analysis of DR4 haplotypes in insulin dependent diabetes (IDD)". United States.
@article{osti_6934836,
title = {Analysis of DR4 haplotypes in insulin dependent diabetes (IDD)},
author = {Monos, D S and Radka, S F and Zmijewski, C M and Kamoun, M},
abstractNote = {Population studies indicate that HLA-DR4 is implicated in the susceptibility of IDD. However, biochemical characterization of the serologically defined DR4 haplotype from normal individuals revealed five DR4 and three DQW3 molecular forms. Hence, in this study, they investigated the heterogeneity of the DR4 haplotype, using B-lymphoblastoid cell lines (B-LCL) generated from patients with IDD and seropositive for DR4. Class II molecules, metabolically labeled with /sup 35/S-methionine, were immunoprecipitated with monoclonal antibodies specific for DR(L243), DQ(N297), DQW3(IVD12) or DR and DQ(SG465) and analyzed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). The isoelectrofocusing (IEF) conditions employed in this study allow representation only of the DR4 haplotype from either DR3/4 or DR4/4 cell lines. The analysis of six different DR4 haplotypes from seven IDD patients, revealed the presence of two DR4 ..beta.. and two DQW3 ..beta.. chains. Three of the six DR4 ..beta.. haplotypes analyzed shared the same DR4 ..beta.. chain and three others shared a different one. Additionally five of the six haplotypes shared a different one. Additionally five of the six haplotypes shared the same DQW3 ..beta.. chain and only one was carrying a different one. Different combinations of the two DR4 and two DQW3 ..beta.. chains constitute three distinct patterns of DR4 haplotypes. These results suggest the prevalence of a DQW3 ..beta.. chain in the small sample of IDD patients studied. Studies of a large number of patients should clarify whether IDD is associated with unique variants of DR4 or DQW3 ..beta.. chains.},
doi = {},
url = {https://www.osti.gov/biblio/6934836}, journal = {Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)},
number = ,
volume = 45:4,
place = {United States},
year = {Wed Mar 05 00:00:00 EST 1986},
month = {Wed Mar 05 00:00:00 EST 1986}
}

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