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Biomedical subjects

H Betuel

Publications and source records attributed to H Betuel.

At least 73 records · Page 4Linked to original sources
PubMed1986

Functional definition of HLA-DR and -DQ epitopes specific for DR2-short, DwFJO haplotype.

T-lymphocyte clones specific for the influenza A/Texas virus were obtained by limiting dilution of activated T cells from an HLA A2/3,B7/39,Cw -/-,DR2-short/2 short,DQw1,DwFJO/FJO donor. Among the proliferating clones studied, and irrespective of their antigenic specificities, most of them were restricted by epitope(s) on HLA-DR molecules present only on DR2-short/DwFJO cells but not on DR2-negative or DR2-long positive (Dw2,Dw12,Dw-) cells. Two clones were restricted by epitopes borne by DQ products. Here again, these epitopes were present on DR2-short/DwFJO but not on DR2-long,DQw1 (Dw2,Dw12) cells, indicating that the DQw1 molecules of DR2-long and DR2-short haplotypes are different. Taken together, these results indicate that the DR2-short,DwFJO haplotype is characterized by both HLA-DR- and DQ-specific molecules. Finally, one clone was restricted by an epitope shared by DR products from DR2 short/DwFJO, DRw11, and DRw13 haplotypes. This latter functional determinant has never been described until now.

Antibodies, Monoclonal↗
PubMed1986

Despite lack of monospecific anti-DRw13 sera, a corresponding class II determinant can be defined by a DRw13 restricted anti-influenza virus T cell clone.

The study of a T3+ T4+ T8- human T cell clone COTC2 with both specific proliferative response and cytolytic activity for influenza A virus infected cells reveals that: the restricting element of this clone is strongly associated with DRw13 molecule(s) as seen by the study of a large panel of antigen presenting cells (APC) and by the observation that monoclonal antibodies (MoAb) specific for DR molecules inhibit its proliferative activity while anti-DQ MoAb do not. These results indicate that there exists a DRw13 associated determinant that can be defined at the functional level by COTC2 recognition despite the absence of monospecific anti-DRw13 serum. In contrast to the results found by other groups, the restriction of this DRw13 restricted clone follows the DRw13 serological definition irrespective of the DW type of the APC. These results indicate that the polymorphism of HLA class II molecules can be further defined at the functional level by monoclonal populations of T cells in conjunction with molecular definition.

Antibodies, Monoclonal↗
PubMed1986

HLA-DR2, -DR5, and DRw6 associated Dw subtypes correlate with HLA-DR beta and -DQ beta restriction fragment length polymorphisms.

DNAs extracted from peripheral blood leukocytes of 24 individuals, selected for their HLA-DR types, -DR2, -DR5, and -DRw6, were analyzed with four restriction enzymes, BamHI, EcoRV, HindIII, and Taq I, using the Southern technique. This panel includes 16 individuals with homozygous typing cells and 8 heterozygous individuals who carry rare Dw subtypes or unusual DR-DQ associations. Eighty-five polymorphic fragments were detected and assigned to the DR or DQ gene families according to their hybridization signals. Thirty-eight fragments (DR or DQ) were found to correlate with single DR or Dw specificities or rare associations such as DRw14-DQw3. Forty-two fragments correlated with the association of immunologically defined specificities. In total, these 85 fragments constituted 44 different patterns, each comprising 1-9 fragments. For each homozygous typing cell a combination of patterns was observed. Fourteen different combinations of 10-20 patterns were found among the 16 individuals with homozygous typing cells, showing that Dw18, Dw19, Dw9, and Dw5 are heterogeneous at the genomic level whereas only the Dw2 individuals tested here are identical.

DNA Restriction Enzymes↗
PubMed1986

[Celiac disease].

Coeliac disease (CD) is a malabsorption syndrome mediated by gluten toxicity. In almost all populations studied CD is strongly associated with HLA.DR3 and to a lesser extent with DR7, the frequency of DR2 is often low. There is a highly significant excess of DR3/DR7 heterozygotes. Although the association of CD with HLA has been known for 15 years the mode of transmission is poorly understood. In multiple case families the segregation of haplotypes is in favour of a recessive mode of inheritance with low penetrance. The rare cases of CD negative for DR3 and DR7 are positive for DR4 and negative for DQw2, ruling out the intervention of DQw2 by linkage disequilibrium. A recent study tends to show an hyporesponsiveness of T lymphocytes from patients to an antigenic extract of gluten.

Celiac Disease↗
PubMed1984

[Articular chondrocalcinosis. Association with B15 antigen].

Antigens of HLA loci A, B and DR were determined in 35 elderly patients with primary articular chondrocalcinosis and compared with a control population. The B15 antigen was present in 13 out of 35 patients, i.e. 37.1% as against 13% of controls (chi 2 = 13.4; pc = 0.05) and the BW21 antigen in 8 out of 35 patients, i.e. 22.8% as against 6.6% of controls (chi 2 = 10.25; pc less than 0.005). These results confirm those of a previous study carried out in the same unit, which showed a 41% incidence of HLA B15 antigen in patients with chondrocalcinosis. The HLA B15 antigen seems to be a marker of imbalanced binding with a susceptibility antigen. Calculation of the relative risk shows that an elderly subject with HLA B15 antigen if about 4 times more liable to articular chondrocalcinosis than a subject without this antigen.

Aged↗
PubMed1984

Genetic epidemiology of coeliac disease.

Segregation analysis favors a gene additive on liability with a frequency of 0.022, which is nearly recessive on the penetrance scale. Less than one-eighth of DR3 and DR7 haplotypes carry a determinant for coeliac disease. There is significant excess of DR3/7 heterozygotes among patients, indicating that the determinants are qualitatively different in DR3 and DR7 haplotypes. Linkage to HLA is highly significant (maximum lod score = 10.9). Evidence for recombination of 8% in males is attributed to residual errors in the model. We suggest an approach to a more precise model.

Celiac Disease↗
PubMed1984

A study of HLA-DR2 associated HLA-Dw/LD specificities.

HLA-Dw2 and Dw12 are both associated with HLA-DR2; however, these specificities accounts for only 86% (161/188) of the DR2+ haplotypes in our North American Caucasian panel. In an attempt to identify new DR2 associated antigenic clusters, we have generated four primed lymphocyte (LD) typing (PLT) reagents in haploidentical familial combination against DR2+ Dw blank haplotypes. These reagents were positively restimulated by 11 of 16 DR2+ Dw blank cells tested, with good discrimination from Dw2 and Dw12+ cells, thus identifying a new antigenic cluster provisionally termed LD-MN2. We have compared the LD-MN2 specificity with the specificity LD-5a defined by two DR2+ HTCs, BAS and REM, (Layrisse, Caracas) which have been included in the pre-1984 Workshop Cluster DB9. Although none of our DR2+ cells gave typing responses to these two HTCs defining LD-5a, PLT studies did indicate an interrelationship between these specificities and with the specificity tb24 defined with the HTC, FJO (Betuel). The LD-5a HTCs, four LD-5a heterozygous cells, and two additional HTCs (WJR-Hansen, Seattle and FJO/tb24--Betuel, Lyon) significantly restimulated the anti-MN2 PLT reagents, though usually not as strongly as the MN2+ cells. MN2+ cells primed against the LD-5a HTCs were restimulated by only the LD-5a+ cells. Dw2+ cells primed against FJO were restimulated by some, but not all MN2+ cells. These results suggest that MN2, tb24, and LD-5a share some determinants, not shared with most cells which type as Dw2 and Dw12, though differing by other stimulatory determinants. These studies emphasize the necessity of studying new antigenic clusters by both PLT and HTC methodologies as well as testing different ethnic groups.

Epitopes↗
PubMed1984

Influence of HLA-A, B, and DR matching on the outcome of kidney transplant survival in preimmunized patients.

The outcome of 893 prospectively typed (HLA-A, B, and DR) and matched cadaveric kidney transplants--all first grafts, with patients being transfused before transplantation--was studied using actuarial survival methods. The effect of HLA-A, B and DR matching was only found to be significantly beneficial to graft survival in the group of 289 presensitized recipients: 70% and 43% graft survival at two years in the case of best-matched (4-6 HLA-A, B, and DR) identities versus mismatched (0 and 1 HLA-A, B, and DR) identities, respectively (P = 0.05). Although a cumulative effect of matching for antigens belonging to the 3 HLA-A, B, and DR series was observed among the group of preimmunized recipients, a trend arose in favor of the prominent role of the HLA-B alleles. No significant difference related to HLA matching was observed in the group of nonsensitized recipients. These results confirm previous observations and support efforts to give priority for matched kidneys to preimmunized patients.

Actuarial Analysis↗
PubMed1983

A possible new HLA-DR allele.

In routine screening of anti-HLA DR reagents, serum 901 was obtained from a woman of negroid origin ten days after delivery of a second child. The spouse was also of black origin. This serum contained polyspecific HLA A and B antibodies. After platelet absorption it reacted with the B cells of 10 out of 119 European Caucasoid panel donors (8.4%) typed for DR1 to DRW10 and for MT1, MT2. Each of these ten donors had only one recognized DR antigen, the other was "blank." Serum 901 gave negative reactions with the homozygous typing cells (HTC) DW1 to DW8. In 18 normal informative Caucasoid families, serum 901 recognized one HLA haplotype in one (or both) parents and segregated with this haplotype in one or more than one child. In one family in which both parents reacted with serum 901, two children were homozygous for this marker and reacted as HTCs. One of these HTCs typed as DW9 and was found to be identical to a DW9.HTC (8W207).

Alleles↗