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D Charron

Publications and source records attributed to D Charron.

246 records · Page 14Linked to original sources
PubMedDate not supplied

Association of type 1 diabetes mellitus with the HLA-DQA1*0301 allele in a Tunisian population.

HLA class II antigens are transmembrane glycosylated heterodimers composed of an alpha and a beta chain. Several of these chains are highly polymorphic. The structural bases of the polymorphism are nucleotide acid substitutions which are situated in the first domain (exon II) of alpha and beta genes. Specific sequences of these domains can be obtained by amplification of genomic DNA using the polymerase chain reaction. Polymorphic sites are recognized by restriction endonuclease treatment and separation of the DNA fragments by polyacrylamide gel electrophoresis. The resulting fragments of different lengths are used to identify different alleles. We used the above technique for typing the HLA-DQA1 alleles in 41 Tunisian diabetic patients. The frequency of DQA1*0301 was greatly increased compared with the control group. This was in agreement with previously published data in Caucasian and Japanese insulin-dependent diabetes mellitus (IDDM) patients, while the significant increase in the frequency of the DQA1*0501 allele was comparable with that of Caucasian IDDM patients but contrasted with a decrease in this allele in Japanese IDDM patients. Our results provide confirmation of the contribution of the DQA1*0301 allele to disease susceptibility in a Tunisian population.

Alleles↗
PubMedDate not supplied

A novel HLA class II molecule (DR alpha-DQ beta) created by mismatched isotype pairing.

Human major histocompatibility complex (MHC) class II molecules are heterodimeric glycoproteins composed of non-covalently associated alpha and beta chains. Only isotype-matched alpha-beta associations have been described in man; these can occur either by cis- or trans-complementation (HLA-DR, DQ, DP). Here evidence is provided for the existence of a new type of hybrid molecule (DR alpha-DQ beta) arising by mixed-isotype pairing in human B-cell lines. Class II isotype-mismatched heterodimers have been recently reported in the mouse after transfection of class II genes, and our data demonstrate that such interisotypic pairing can occur in untransfected cells. This crosspairing greatly enhances the repertoire of the class II antigens that regulate immune responses and leads us to reconsider the HLA-disease association.

Antibodies, Monoclonal↗
PubMedDate not supplied

Signalling via MHC class II molecules modifies the composition of GEMs in APC.

Major histocompatibility complex (MHC) class II molecules are responsible for peptide presentation to helper T lymphocytes and as such play an essential role in the immune response. These molecules transmit intracellular signals leading to diverse consequences in B lymphocytes including proliferation and apoptosis. Recent studies have revealed that glycolipid enriched membrane microdomains (GEMs) behave as signalling platforms for a variety of lymphocyte receptors. We have quantified human leucocyte antigen (HLA)-DR molecules localized in GEMs in human B lymphocytes. Use of a model imitating the interaction of HLA-DR with a T-cell receptor (TCR) modified the constituents of the HLA-DR-enriched GEMs. Confocal microscopy demonstrated a recruitment of HLA-DR and the ganglioside GM1 at the site of HLA-DR interaction with the stimulating ligand. Moreover, cholesterol depletion efficiently impaired this recruitment. Co-localizing proteins detected in HLA-DR-enriched GEMs include protein kinase C (PKC)-delta and actin. These data reveal that MHC class II antigens are localized in GEMs in mature human B lymphocytes and indicates that the formation of the immunological synapse regulates the composition of HLA-DR enriched GEMs in the antigen presenting cell (APC).

Actins↗
PubMedDate not supplied

Signal transduction via MHC class II antigens on B lymphocytes.

The role of the MHC class II antigens in the activation of resting human B lymphocytes (B-Go) was examined with respect to both early and late events in the activation process. The (Ca2+)i induced by anti-IgM was enhanced in the presence of, or following pre-incubation with, an anti-MHC class II DR antibody (D1.12). Pre-incubation with a sepharose conjugated antibody (Seph.-D1.12) augmented the proliferation of B-Go in response to a sub-optimal concentration of anti-IgM. The 2D PAGE profile of B-Go differed from that of in vivo activated B lymphocytes. The 2D PAGE profile of B-Go activated by Seph.-D1.12 was not identical to the profile of B-Go activated by either anti-IgM or PMA. These data suggest that the activation of B-Go via the class II antigens shares part of the pathway of anti-IgM induced activation but does not follow an identical pathway.

Antibodies, Monoclonal↗
PubMedDate not supplied

Diabetes patient education research: an integrative literature review.

PURPOSE: The purpose of this study is to summarize the accumulated state of knowledge in the area of diabetes patient education research and highlight important issues that research has left unanswered. METHODS: An integrative literature review was conducted on the topic of diabetes patient education between the years 1985 and 1998. Keywords used in the computerized search were diabetes mellitus, patient education, health education, research, and behavior change. The databases searched were MEDLINE, CINAHL, HealthSTAR, EMBASE, and CHID-HE. A total of 78 papers were reviewed. RESULTS: Most studies lacked a theoretical framework and the majority of studies were conducted in an outpatient setting. HbA1c was the most frequently employed outcome measure, with little, if any, description of the interventions. CONCLUSIONS: Much has been learned in terms of the effectiveness of diabetes education on improving knowledge. However, other topic areas and outcomes need further exploration.

Diabetes Mellitus↗
PubMedDate not supplied

Familial versus sporadic longevity and MHC markers.

We have studied the polymorphism of HLA-A, B, in 2 elderly populations (> or = 90 years) compared to a control series of 429 healthy unrelated individuals less advanced in age. The aged population issued from the CHRONOS cohort consisted of 336 centenarians without familial history of longevity, and 102 nonagenarians index cases randomly selected from families. Almost all individuals (310) were previously typed for HLA-DRB1. The increased allelic frequency of HLA DR11 was observed in familial nonagenarians (18.3%) compared to controls (10%) (p < .001) and to sporadic centenarians (11.8%). Concerning HLA Class I alleles, only rare alleles (A30, B70) remain significantly different from the controls after correction of the p value. No distortion of the Mendelian sharing of haplotypes was observed among sibling pairs of familial nonagenarians. A protective effect of the HLA-DR11 molecule itself, presenting adequately immunogenic-infectious peptides, is probable rather than genes in disequilibrium. Our study strongly supports the heterogeneity of longevity, the association of HLA-DR11 in its familial form in aged populations.

Adult↗
PubMedDate not supplied

European genetic study on rheumatoid arthritis: is there a linkage of the interleukin-1 (IL-1), IL-10 or IL-4 genes to RA?

UNLABELLED: The genetic predisposition for rheumatoid arthritis (RA) is only partly explained by the HLA locus and most genetic factors involved in the susceptibility (and/or severity) of the disease await further identification. The first European genome scan in RA families provided suggestive evidence for linkage with a region (3.1/3q13) on chromosome 3, but many other potential RA susceptibility genes have yet to be analysed. AIMS: To perform a linkage analysis with microsatellite markers located in the vicinity of the interleukin-1 (IL-1) gene superfamily, the IL-10 gene and the IL-4 gene cluster which might be considered putative candidate loci for RA. METHODS: 107 Caucasoid European RA sibpairs from 90 nuclear families were genotyped for markers flanking the genes for the IL-1 superfamily, IL-10 and the IL-4 gene cluster. Linkage analysis based on the identity by descent (IBD) in affected siblings was analysed with the program SIBPALNA. Affected sibpairs were stratified according to the identity by state (IBS) for three markers in the HLA region (DRB1 oligotyping, D6S276 and TNFa microsatellites) and to the presence/absence of erosive disease on X-ray examination. RESULTS: Analysis of the whole family set showed an excess of allele sharing for markers of the IL-1 gene cluster (IBD 60%; P = 0.012) but not for IL-10 or IL-4. After stratification, the evidence of linkage to IL-1 was restricted to HLA concordant sibpairs (n = 32; IBD 70%; P = 0.006). Some evidence of linkage to IL-10 was also observed in HLA concordant sibpairs (IBD 66%; P = 0.03) and in sibpairs with erosive disease (n = 61; IBD 62%; P = 0.02). CONCLUSIONS: We found suggestive evidence of linkage of RA to the IL-1 locus. The increased linkage to IL-1 and IL-10 in HLA-identical sibs suggests a possible interaction between these cytokines and the HLA loci. Moreover IL-10 could interact with HLA factors in predisposing to erosive disease. These results need to be tested in additional families for consistency and replication.

Arthritis, Rheumatoid↗
PubMedDate not supplied

A possible linkage of HLA-DRB haplotypes with Tiopronin intolerance in rheumatoid arthritis.

To investigate the relationship between HLA class II genotypes and toxic intolerance during treatment with Tiopronin, a slow-acting drug used in the treatment of rheumatoid arthritis (RA), we studied 40 patients who were divided into two groups: a group of 22 patients without side effects and a group of 18 patients with intolerance to Tiopronin. The PCR-RFLP method was used to determine the HLA-DR, DQ and DP genotypes. The patients in the two groups had similar genetic backgrounds with an expected high frequency of DRI and DR4 alleles. However, DR1/DR4 heterozygosity was significantly increased in patients with intolerance (p = 0.03, Odds Ratio = 10.5). In addition, one intolerant patient had a DR1/DR7 genotype which shared DRw53 (DRB4*0101) with DR1/DR4. Furthermore, two subtypes of DR5, DRB1*1102 and DRB1*1201, were increased among intolerant patients (11.1% vs 0%, p = 0.03, OR = 13.97). In total, DR1/DRw53 heterozygotes, DRB1*1102 and DRB1*1201 represented 61.1% of intolerant patients. Therefore, a detailed HLA class II typing might be useful before RA treatment by Tiopronin to predict and avoid toxic side effects in the patients with increased risk. Further investigation is currently underway.

Adult↗