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Biomedical subjects

J Dausset

Publications and source records attributed to J Dausset.

At least 127 records · Page 7Linked to original sources

[Alpha genes of the T cell receptor: a possible implication in genetic susceptibility to multiple sclerosis].

Multiple sclerosis (MS) is a neurological disease in which 60% of patients are DR2 (versus 20% in controls). Restriction fragment length polymorphism (RFLP) associated with T cell receptor alpha-chain and beta-chain genes have been analysed in a sample of 46 MS patients and compared with those of 142 controls. The alpha-chain gene polymorphism is localized to the V-J region and consists of 3 Bgl II alleles (alpha a = 3.2 kb; alpha b = 2.9 kb; alpha c = 2.8 kb). A significant difference was found in the distribution of these three alleles since 97% of DR2 patients versus 60% in DR2 non-MS individuals were found to be homozygotes alpha a/alpha a. These results suggest the influence of T cell antigen receptor germ line repertoire on the etiopathology of this disease.

Alleles↗

[HLA A-B and DR in dilated myocardiopathies].

HLA A, B typing was performed in 90 patients (90 men, 10 women), and HLA DR typing in 49 patients with dilated cardiomyopathy in order to test the hypothesis that a particular genetic background may influence the immune response in that disease. No significant difference in phenotype frequency of the HLA A and B antigens was observed between patients and control population. In contrast, the HLA DR4 antigen was significantly more frequent among patients (40.8% vs 23.8%, p corrected less than 0.001). The results suggest that genetic factors play a role in the pathogenesis of dilated cardiomyopathy, and that since DR4 is frequently associated with auto-immune manifestations, a modified immune response is possible in dilated cardiomyopathy.

Adolescent↗

[Setting-up a national file of bone marrow volunteer donors].

The lack of HLA matched sibling donors has become a problem. Recent improvements suggest the feasibility of marrow transplantation from unrelated donors. A program to obtain volunteer bone marrow donors has been developed. A total of 3,853 HLA A B typings were performed. A search for 83 patients was initiated; 51 of them had one or more HLA A and B (61%), 8 HLA A, B and DR antigen identical donors, 2 did not react in mixed lymphocyte culture. This experience confirms the necessity of increasing the donor file but the size remains to be established.

Bone Marrow Transplantation↗

First trimester prenatal diagnosis of 21-hydroxylase deficiency by linkage analysis to HLA-DNA probes and by 17-hydroxyprogesterone determination.

The close genetic linkage between the gene for congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency and HLA genes allowed us to use the polymorphism of this system as a marker of the disease. HLA genotyping can be performed by using restriction enzyme fragments hybridized with specific probes instead of serologic methods. In seven pregnancies at risk for 21-OH deficiency, a first trimester prenatal diagnosis has been performed by determining the fetal genotype by linkage analysis of DNA from chorionic villi using HLA class I and class II probes. In four of these pregnancies, determination of 17-OH progesterone in first trimester amniotic fluid afforded a complementary approach to the diagnosis.

17-alpha-Hydroxyprogesterone↗

Associations between restriction fragment length polymorphisms detected with a probe for human 21-hydroxylase (21-OH) and two clinical forms of 21-OH deficiency.

DNAs from unrelated healthy individuals and unrelated individuals affected with 21-hydroxylase deficiency (congenital and late-onset adrenal hyperplasia) were digested with seven restriction enzymes and hybridized with a cDNA probe specific for human 21-hydroxylase genes. Associations were found between restriction fragments and the two forms of the disease: The late onset form is associated with a double dose of a 14 kb fragment generated by EcoRI and with a triple dose of a 3.2 kb fragment generated by Taq I in patients with HLA B14 haplotypes; The classical congenital form is negatively associated with the 14 kb fragment and with a 3.7 kb fragment generated by Taq I in patients with HLA Bw47 haplotypes. A 3.2 kb Taq I fragment is negatively associated with the HLA B8 haplotypes. The other five enzymes tested give no polymorphisms or polymorphisms without correlation with the two forms of the disease.

Adrenal Hyperplasia, Congenital↗

A study of the HLA-D region in patients with classic Kaposi's sarcoma.

The HLA-D region in nine Sardinian patients with classic Kaposi's sarcoma was studied with two restriction enzymes, Eco RI and Eco RV, and two cDNA probes, DR beta and DQ beta. A total of 41 polymorphic restriction fragments were identified. One, an 11.5 kb Eco RV DQ beta fragment, was present in three of the patients but in none of the controls; a second, an 8.0 kb Eco RV DR beta fragment, was present in six patients and all the controls. No single fragment was identified which was significantly over or under-represented in either group.

Alleles↗

HLA-DR2-associated Dw subtypes correlate with RFLP clusters: most DR2 IDDM patients belong to one of these clusters.

Two variants of the serologically defined HLA-DR2 specificity have been reported: DR2 long and DR2 short. Distinct HLA-DR2-associated Dw subtypes have been described at the cellular level. In the Israeli population, DR2 individuals may be grouped into three clusters: DR2/Dw2, DR2/Dw12, and DR2/Dw"AZH". A new approach for the study of the polymorphism of HLA class II genes is to investigate restriction endonuclease fragments obtained from genomic DNA with specific class II cDNA probes. Previous analysis of DQ beta restriction endonuclease fragments subdivided the DR2 haplotypes into two subsets: a DQR1-positive subset and a DQR2.6-positive subset. These two subsets behave in the population as alleles that split HLA DQw1. In the present study, we have analyzed class II DQ alpha, DQ beta, and DR beta restriction fragment length polymorphism (RFLP) in HLA-DR2/Dw-typed healthy, unrelated Israeli individuals, as well as in 11 French HLA-DR2 insulin-dependent diabetes mellitus (IDDM) patients and 11 French DR-matched controls. Three DQ beta allelic clusters (DQR2.6, DQR1, and DQR12) were observed among the DR2 haplotypes and clearly correlated with Dw2, Dw"AZH", and Dw12, respectively. The vast majority of the DR2 IDDM patients (9 out of 11) fit into the DQR1 cluster which correlates with Dw"AZH", while only two patients (2 out of 11) belong to the DQR2.6 cluster (Dw2-like). In contrast, among 11 DR-matched healthy controls, 9 belonged to the DQR2.6 cluster and only 2 belonged to the DQR1 cluster. These studies establish the correlation between the DR2-associated Dw subtypes with specific RFLPs, and indicate that the frequency of the DQR1 subset which correlates with Dw"AZH" is increased in DR2 IDDM patients.

DNA Restriction Enzymes↗

Correlation between an HLA-DQ alpha length polymorphism of messenger RNA and serologically defined specificities (DQw1, DRw53, DR3+5).

mRNAs for the two chains of the HLA-DQ molecule were analyzed, in particular the DQ alpha mRNA whose polymorphism had previously been suggested (Schenning et al. 1984). Northern blot transfers of the mRNA of 12 LCLs and of B lymphocytes from a healthy donor were carried out. We report that a length polymorphism of DQ alpha mRNA exists, and we show that it can be correlated with serologically defined specificities (DQw1, DRw53, DR3+5). This correlation could be explained by a linkage disequilibrium, as these specificities are considered to be different from those carried by the DQ molecule (except for the DQw1 specificity).

DNA Restriction Enzymes↗

Human autologous rosette-forming cells. V. Study of MHC control in erythrocyte-lymphocyte interaction.

The role of the major histocompatibility complex (MHC) in human autorosette formation was studied. On a large series of healthy subjects who were typed for HLA antigens, we tested in blind rosette formation with 90 autologous and 295 allogeneic red blood cells (RBC). We found that the mean levels of auto- and allorosettes were similar, being significantly higher in females than in males. However, we failed to find any role for blood group antigens and any involvement of HLA antigens in the interactions between lymphocytes and RBC in rosette formation. Moreover, high or low autorosette levels were not associated with a particular HLA allele. The comparison of individual percentages of auto- and allorosettes indicated that 51% of the subjects displayed identical levels of auto- and allorosettes whereas 29% formed preferentially rosettes with auto- rather than allo-RBC and 20% exhibited lower autorosette than allorosette levels. Among the group of subjects who were better responders for autorosettes than allorosettes, we found an increased frequency of the haplotype A29, B44. Taken together these findings suggest that in contrast to the murine situation, the autorosetting phenomenon in humans is not HLA restricted.

Erythrocytes↗

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↗

Recombinant interferon alpha can induce rearrangement of T-cell antigen receptor alpha-chain genes and maturation to cytotoxicity in T-lymphocyte clones in vitro.

T-cell receptor genes are found in the germ-line configuration as well as in rearranged forms, as detected in T lymphocytes by different patterns in Southern blot analysis. We have recently shown that cytotoxic T-lymphocyte (CTL) "precursor" clones, in which rearrangements are not detected in the gene encoding the T-cell receptor alpha-chain (TCRA), acquire specific lytic function induced by treatment with recombinant interferon alpha or gamma. We now report that, coincident with the acquisition of cytotoxic function by the precursor CTL clone; recombinant interferon alpha appears to induce a rearrangement of TCRA. In addition, in a mature CTL clone (i.e., one already showing lytic function) in which one TCRA allele is rearranged, treatment with recombinant interferon alpha appears to induce a new rearrangement of a TCRA gene.

Cell Differentiation↗

Two DR beta allelic series defined by exon II-specific synthetic oligonucleotide genomic hybridization: a method of HLA typing?

Comparisons of exon II HLA-DR beta sequences have shown that nucleotide variations are principally clustered within the following three regions: V1 (amino acid 8-15), V2 (25-32), and V3 (70-77). V1, V2, and V3-derived 24-mers have been synthesized, the DR beta sequences coming from DR1, DR3, Drw6, DR4, DR5, and DRw53 haplotypes. Each oligonucleotide was hybridized to Pvu II-digested DNA samples from 13 HLA genotyped families; therefore, 52 haplotypes have been investigated. Six polymorphic Pvu II fragments were detected, constituting two allelic series probably corresponding to the beta 1 and beta 2 locus of the DR region. The first series (beta 1) comprises a minimum of nine alleles while the second series (beta 2), which is less polymorphic, comprises at least four alleles. Certain patterns correlate perfectly with certain DR specificities, whereas other patterns define new subdivisions as in DR3 and DRw6 haplotypes. Although it appears that some mismatches do not always prevent hybridization in the conditions used in this work, this method will provide in many instances a convenient tool for HLA-DR typing.

Alleles↗

[Organ transplantation in France in 1984 (activity report of France-Transplant)].

Nine hundred and seventy four renal transplantations were performed in 1984, thus attaining a total 7927 grafts made in France at the end of 1984. The numbers of heart transplantations (77), to which 100 prospects in 1985 can be added, as well as liver grafts (13) plus 50 prospects in 1985, are showing a spectacular increase. Although the considerable improvement of heart graft and liver graft results can be attributed, essentially to the use of Cyclosporine, this trend can be dependent in the case of kidney transplantations also on transfusions before and on a better HLA-B DR compatibility which can in optimal situations represent a respective gain of 10% and 15% of graft survival.

Adult↗