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Biomedical subjects

H Betuel

Publications and source records attributed to H Betuel.

At least 19 recordsLinked to original sources
PubMed1992

[Lymphoproliferative syndromes associated with Epstein-Barr virus in transplantation].

We report 23 cases of lymphoproliferative diseases which occurred among 2,100 patients with kidney or combined kidney+pancreas transplant. Eleven patients developed a severe diffuse disease within the first 3 months post-transplantation; immunoblastic B cells of recipient origin infiltrated the bone-marrow, transplanted organs, liver, spleen, lymph nodes, lungs, and brain; immunoglobulin abnormalities with fever, leuko-thrombocytopenia and liver dysfunction constituted the symptoms; all patients received anti-lymphocyte globulins; 9 patients were also treated with cyclosporin. Three out of 6 tumors analysed were monoclonal. Epstein-Barr virus was present in 3 lesions analysed. Treatment consisted of cessation of immunosuppressive therapy. Nine patients died with lactic acidosis. Five patients had a less severe form. Seven patients had solid tumors involving the tonsils, lungs (2), lymph nodes (2), and bladder, 8 months after transplantation. All patients received cyclosporin; 4 also received anti-lymphocyte globulins and 3 OKT3. Tumor cells were immunoblasts expressing B cells markers at a late stage of B cell differentiation; 4 tumors were monoclonal. C myc was negative. Treatment consisted of cessation of immunosuppressive therapy, antiviral agents, and monoclonal antibodies (mAb): anti-CD21 and anti-CD24 mAb therapy was followed by cure of the lymphoma in 1 patient, by transient remission in a second one and by failure in the third patient. Two patients had a recurrence of the lymphoma and received chemotherapy; 2 patients died of the lymphoma, 1 died of unrelated cause; 4 are alive, 3 of them having a good graft function.

Antigens, CD↗
PubMed1992

HLA-A29.2 subtype associated with birdshot retinochoroidopathy.

Birdshot retinochoroidopathy is strongly associated with HLA-A29. This antigen can be divided into two subtypes, A29.1 and A29.2, using an immunoprecipitation method succeeded by one-dimensional electrofocusing gel electrophoresis. We reviewed the HLA typings of 58 white French patients who had birdshot retinochoroidopathy. Of these 58 subjects, 54 (93.1%) had HLA-A29 with a relative risk of 157.30. We further analyzed the HLA-A29 subtypings of 33 patients with birdshot retinochoroidopathy. Evaluation of the results showed that HLA-A29.2 subtype was present in all patients (100%). We concluded that the absence of HLA-A29.1 subtype is statistically significant (P less than .01) in this study of HLA-A29 subtyping.

Adolescent↗
PubMed1992

Apparent HLA DR triplet due to the coexpression of a DRB5-encoded molecule on a DR1 haplotype.

HLA DR1 molecules are coded by a single polymorphic DRB1 gene. We have observed rare DR1 cells in one Caucasoid family and three unrelated individuals that also reacted with some anti-DR2 sera. Since the second DR antigen was normally expressed, these cells appeared as triplets. Contrary to serology, the cells were not typed by HTCs defining Dw2, Dw12, and Dw21. Further investigations on these unusual DR1+2* haplotypes were conducted by DNA oligotyping and by sequencing of the DRB first-domain exon. The results showed that these DR1 haplotypes, besides their DRB1*0101 allele, carried also a DRB5*0101 allele.

Adult↗
PubMed1992

Alloantisera can detect some of the variants of HLA DRw13 identified by oligotyping.

Oligotyping has revealed a considerable polymorphism of HLA DRw13; so far, 5 alleles coded by DRB1 have been identified. An even greater number of haplotypes are apparent when considering the association of DRw13 with alleles coded by DRB3 and DQB1. Serology can now define some of these variants which had formerly escaped detection. We have tested by serology and by oligoprobes 66 genotyped Caucasoid cells comprising the known DR and DQ alleles. Among the 28 DRw6 cells, 10 different haplotype patterns were selected, of which 8 concern DRw13 and 2 DRw14. Four variants of DRw13 were represented: DRB1 *1301, *1302, *1303 and *1305 associated with usual and with uncommon alleles belonging to DRB3 and to DQB1. We have centered our analysis on 19 sera of the XIth Workshop defining DRw6. Two sera (639, 826) were noteworthy since they reacted with certain subtypes of DRw13 and with DRB1 *1102, *1103 only, the other DR specificities remaining negative.

Amino Acid Sequence↗
PubMed1992

In utero transplantation of stem cells in humans: immunological aspects and clinical follow-up of patients.

Four human fetuses were treated by transplantation of human fetal liver stem cells. Two of them had severe immunodeficiency disease and the two other ones had thalassemia major. Three of these in utero transplants were followed by engraftment. The three patients are now born: the first one is now very healthy thanks to the reconstitution of cell-mediated immunity associated with this transplant, and he lives normally at home; the two other ones, who have been more recently treated, have a significant improvement of their condition and they also live normally at home. This procedure, for the first time used in humans, has therefore demonstrated its feasibility and its efficacy: during early fetal development, foreign cells engraft readily and may result in cure or significant correction of a large variety of inherited diseases.

Blood Transfusion, Intrauterine↗
PubMed1992

The bare lymphocyte syndrome.

The bare lymphocyte syndrome is a combined immunodeficiency resulting from the lack of expression of either class I or class II HLA antigens at the cell surface. The main clinical manifestations are infections of the respiratory or the digestive tract. The immunodeficiency involves the absence of antibody formation and the absence of cell-mediated response, to specific antigen, contrasting with virtually normal transplant immunity to allogeneic determinants. The responsible gene(s) is not born by chromosome 6. The best treatment appears, at the present time, to be in utero stem cell transplantation into the sick fetus, and it may, in the future, be gene therapy.

Child, Preschool↗
PubMed1991

HLA-DRw11, DQw7 has four cellular subtypes revealed by homozygous typing cells and undetected by restriction fragment length polymorphism.

HLA-DRw11 is in strong linkage disequilibrium with DQw7. We have investigated the heterogeneity of DRw11, DQw7 by cellular typing and by HLA cDNA probes. The results obtained by local and other homozygous typing cells in four informative Caucasoid families and 20 genotyped individuals demonstrate the existence of at least four different cellular subtypes. The frequency of DRw11, DQw7 is 25.7% with the following distribution of subtypes: Dw5 (17.3%), JAC (4.2%), JVM (2.8%), TIS (0.7%), and blank (0.7%). JVM (10W 9039) has been previously described; TIS (10W 9042) and JAC are postulated new specificities from our laboratory. None of these subtypes typed for DRw11, DQw1 cells. The cellular heterogeneity contrasts with the absence of polymorphism observed by serology and by restriction fragment length polymorphism after hybridization with DRB, DQA, and DQB probes. Variation in amino acids of the DRB1 chain has been reported for at least three variants: Dw5, JVM, and TIS (more recently).

Amino Acid Sequence↗
PubMed1991

Diversity among DRw13 DQw7 haplotypes as revealed by serology Dw typing and restriction fragment length polymorphism.

HLA-DRw13 is in linkage disequilibrium with DQw6; an unusual association, DRw13 DQw7, is found in 2% of our Caucasoid population. Investigation of genotyped individuals and of families by two allosera and by Dw typing revealed two subtypes: one recognized by homozygous typing cell HAG and by two allosera, the other subtype remained unreactive with both reagents. Analysis of DNA fragments with DNA probes indicated that the HAG-negative subset had DNA fragments in common with DRw6 while the HAG-positive subset shared DNA fragments with DR5. However, all DRw13 DQw7 cells are Dw24 as seen by hybridization with DRB probe.

Genetic Variation↗
PubMed1991

Additional complexity within the HLA-D region: sequence analysis of two new DRw13-DQw7 haplotypes.

HLA-DRB1 is by far the most polymorphic locus within the HLA-D region with now well over 40 alleles. Nearly one fourth of these alleles are subtypes of DRw6, and these are in most cases undetectable by routine typing procedures. In this paper we present the molecular characterization of two new Caucasian DRw13-DQw7 haplotypes by DNA sequencing of the polymorphic first domain exons of DRB1 and DRB3 loci. The first haplotype, DRB1*1301-DRB3*0101-DQB1*0301, has arisen by a recombination between locus DRB1 from a DRw13-DQw6 haplotype and DQA1 from a DR4-DQw7 haplotype, as determined by DNA sequencing, DQ oligotyping, and restriction fragment length polymorphism typing. The second haplotype, DRB1*1305-DQB1*0301, is characterized by the novel DRB1*1305 allele differing from DRB1*1301 by three amino acids. It probably arose by a gene conversion event between a DRw13-DQw6 allele and DRB1*1101. This allele represents a DRw11/DRw13 hybrid DR molecule with a DRw13 serological epitope in the second hypervariable region and a Dw5 cellular epitope in the third hypervariable region. As determined by sequencing of locus DRB3, this allele is associated with DRw52b. Our molecular analysis of the complex HLA-DRw13 group now allows unambiguous DNA typing of all five DRw13 alleles with seven oligonucleotides, a significant improvement in the context of organ transplantation.

Amino Acid Sequence↗
PubMed1991

The value of platelet transfusions as preparation for kidney transplantation.

The role of platelet transfusion as a preparative method for kidney transplantation is still a matter of debate. Two groups of 28 male patients transplanted between 1983 and 1988, paired for age, date of transplant, absence of anti-HLA antibody and immunosuppressive therapy have been compared. Group I was given 5 purified platelet transfusions at 1-week intervals before transplantation. Each transfusion contained 7.6 x 10(6) platelets contaminated by less than 1 leukocyte in 10(5) platelets. Group II received from 3 to 5 whole blood transfusions. In all cases it was a first transplant from cadaveric donors and previously untransfused patients before entering the protocol. No patient in group I developed cytotoxic antibodies. Acute tubular necrosis occurred with the same incidence in group I and in group II but was more severe and longer in group I, requiring hemodialysis in 62.5% and only 22% in group II. ATN was significantly associated with graft loss in group I (P less than 0.05). The total number of rejections and the number of patients undergoing rejection were not significantly different in both groups. However, the intensity of rejection was significantly higher in group I with 41% (21/51) of severe or irreversible rejections versus 9/46 (19.5%) in group II (P less than 0.05). The first rejection occurred significantly earlier in group I than in group II since 75% of the first rejection episodes occurred in the first 10 days versus 38% in group II (P less than 0.02) with a mean delay of 12.8 +/- 3.2 and 19.10 +/- 3.3 days, respectively. Although platelet transfusions are devoid of leukocytes the incidence of CMV infection was not significantly different in both groups: 57% in group I and 68% in group II. Purified platelet transfusions did not induce humoral immunization but lack of sensitization does not imply indefinite graft prolongation. Because platelets do not carry class II antigens, purified platelets transfusions represent a useful model to analyze the role of class I antigens alone in the induction of unresponsiveness in organ transplantation.

Adult↗
PubMed1991

[HLA-A29 sub-types and "Birdshot" choroido-retinopathy susceptibility: a possible "resistance motif" in the HLA-A29.1 molecule].

The Birdshot choroidoretinopathy (BSCR) is an ocular disease strongly associated with HLA-A29. The HLA-A29 specificity can be split using immunoelectrofocusing in two subtypes A29.1 and A29.2. BSCR susceptibility is exclusively linked to the HLA-A29.2 molecule. The sequence of HLA-A29.2 was established (EMBL X60108 and found to be identical between patients and healthy individuals. A single difference was found (H----D) 102) in the extra cellular domains between HLA-A29.2 and HLA-A29.1. The HLA-A29 sub-types shares the consensus HLA class I sequence (D102). The mutation exhibited by HLA-A29.1 (H102) is unique to that molecule. The ancestral type is thus HLA-A29.2 that confers the susceptibility to BSCR whereas HLA-A29.1 has arisen from a more recent mutation conferring resistance to BSCR. Another single amino-acid difference between HLA-A29.1 and HLA-A29.2 was found in the intracytoplasmic part of the molecule, HLA-A29.2 exhibiting the HLA-A consensus sequence whereas A29.1 shares with AW33.1 the mutation S----F321. In addition, the A29 specificity was assigned to L and Q amino-acids at position 62-63, which can interact with peptides into the binding groove. No specific T or B epitope of susceptibility could be considered involving the region of the mutation discriminating HLA-A29.2 from HLA-A29.1. The HLA-A29.1 mutation is unable to interact with the T cell receptor and did not seem to induce significant structural changes in the peptide-binding groove. Conversely, its position suggests that the A29.1 mutation might interfere with the binding of an accessory molecule, the CD8 molecule being the most likely candidate for that role.

Amino Acid Sequence↗