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M Jeannet

Publications and source records attributed to M Jeannet.

At least 37 records · Page 2Linked to original sources
PubMed1996

Pretransplant cytotoxic donor T-cell activity specific to patient HLA class I antigens correlating with mortality after unrelated BMT.

Unrelated bone marrow transplantation (BMT) is associated with increased post-transplant complication rates, partly because more transplantation antigens are mismatched than in HLA-identical related BMT. We have shown previously that the cytotoxic T-lymphocyte precursor (CTLp) test performed before transplantation specifically detects HLA class I mismatches demonstrating its usefulness for the identification of new HLA class I alleles. In this study we analysed the clinical relevance of the CTLp test in 41 patients who underwent unrelated BMT between 1990 and 1994. All patient-donor pairs were HLA-A, -B, -DR compatible as defined by AB-serology and oligotyping for DR1-14. The host-reactive CTLp test was performed using previously frozen peripheral blood mononuclear cells (PBMC) as stimulators and PHA blasts as target cells. We found 10 CTLp-positive and 31 CTLp-negative patient-donor pairs. Between the two groups there were no significant differences for age, diagnosis, sex, preconditioning and GvHD prophylaxis. The clinical results for the CTLp positive and the CTLp negative transplants were: severe acute GvHD III-IV 67% and 26% (P = 0.0315), transplant-related mortality 60% and 26% (P = 0.0085), and patient survival at 3.5 years 10% and 54% (P = 0.0006). Seven patient-donor pairs were mismatched for HLA-DR and/or -DQ subtypes. Only one of these seven class II mismatched pairs had a positive CTLp test. In the remaining nine CTLp positive pairs the CTL reactivity was directed against HLA-A, -B or -C antigens, revealing a statistically significant (P < 0.005) correlation between the CTLp frequency and HLA class I matching. In conclusion, the CTLp test helped to select optimally matched bone marrow donors and was particularly useful in association with high resolution oligotyping for DR- and DQ-subtypes for precise matching of both classes of HLA antigens.

Adult↗
PubMed1995

Heterogeneity of HLA-B35. Oligotyping and direct sequencing for B35 subtypes reveals a high mismatching rate in B35 serologically compatible kidney and bone marrow donor/recipient pairs.

We used a simple HLA-B35 PCR/SSO-oligotyping procedure, combined with exon 3 direct sequencing for the analysis of B35 subtype frequencies in our population, and for the evaluation of the degree of B35-subtype compatibility in serologically matched unrelated bone marrow and kidney transplant pairs. B*3501 was the most frequent allele (0.6), followed by B*3503 (0.19), B*3502 (0.13), B*3508 (0.07), and B*3505 (< 0.01). HLA-B35-subtype matching of donors and recipients was strongly dependent on the stringency of ABDRB1 matching. Among 10 kidney donor/recipient pairs, only 30% were B35-subtype-matched. Due to the lack of ABDRB1 haplotype matching, this low degree of matching was not better than what would be expected on the basis of the subtype frequency distribution in the population. In contrast, HLA-B35 subtype compatibility was higher in unrelated bone marrow donor/recipient pairs that were serologically ABDR-matched: 30 of the 62 (48.4%) B35-positive combinations tested were B35-subtype-compatible. When all patient/donor plus donor/donor combinations (n = 160) were taken into account, 46% of the ABDR-matched pairs were B35-subtype-compatible. When only pairs that were DRB1/DRB3/DRB5-subtype-matched by oligotyping (n = 62) were considered, 71% were B35-subtype-compatible. The fact that a significant percent of patient/donor pairs matched by conventional HLA-typing are found incompatible, as shown here for B35, explains the difficulties in assessing the beneficial effect of HLA matching in transplantation.

Base Sequence↗
PubMed1995

[Immunological aspects of kidney transplantation in Switzerland 1981-1992. Swiss Transplant Work Group Kidney Transplantation].

Every year some 200-260 kidney transplants are performed in Switzerland, improving the quality of life of patients with end stage renal disease. The current organ shortage is delaying transplantation of the 400 patients on the waiting list, a situation which calls for optimal utilization of the available donor kidneys. It is well established that AB0-compatibility, negative cytotoxic crossmatch, and optimal immunosuppressive therapy including cyclosporin A are important for a favorable clinical outcome. To identify further factors influencing transplant outcome, we undertook a retrospective study of all 1656 transplants to which the above criteria applied. We defined transplants matched for at least 1A, 1B, and 1DR HLA antigen as the better matched, and the remainder as the less well matched grafts. In patients who were not or only weakly immunized to alloantigens, the 5-year graft survival probability was 0.78 versus 0.69 for the better versus the less well matched transplants (p < 0.005). The strongly immunized patients did not, however, show a significant association between the degree of HLA matching and graft survival, presumably because there were more immunized patients in the HLA matched group. As expected, the patients previously immunized to alloantigens showed significantly reduced graft survival early after transplantation. Positive CMV serology, sex mismatch, and cold ischemia time did not correlate with graft survival. Compared to results obtained in the USA or Germany, the survival time of donor kidneys transplanted in Switzerland was significantly increased. Factors contributing to the good results in Switzerland are discussed. Future goals are reduction of alloimmunization and optimized HLA compatibility.

Cyclosporine↗
PubMed1995

Renal transplantation to sensitized patients: decreased graft survival probability associated with a positive historical crossmatch.

Sensitized patients may reject renal transplants at a tempo or with a force dictated by their previous exposure to alloantigen. The patient's pretransplant alloimmunization status is usually assessed by the measurement of panel reactive antibodies (PRAs) and by the crossmatch. The test results using current patient's sera are of considerable predictive value. In contrast, the relevance of historical sera is much debated. To further investigate the correlation of PRA and crossmatch with clinical outcome, 852 cadaveric kidney transplants were evaluated. As expected, graft survival was significantly longer (p = 0.01;logrank test) in nonimmunized patients (n = 516) compared to immunized patients with more than 10% PRA (n = 297). Patients with persistently positive PRAs (n = 171) were then compared to patients with positive historical but negative current PRAs (n = 126). Interestingly, their graft survival was practically identical. Finally, transplants across a positive historical T cell crossmatch (n = 39) had a significantly reduced graft survival (p = 0.015) compared to transplants in immunized patients (n = 297, all T cell crossmatch negative). Thus, this study confirms the increased risk in sensitized patients and shows that the antigen specific immunological memory is of clinical relevance even if donor specific antibodies are not detectable in current sera.

Adult↗
PubMed1995

Application of a polymorphic Y microsatellite to the detection of post bone marrow transplantation chimaerism.

A highly sensitive Y-microsatellite amplification system was developed for the detection of post bone marrow transplantation (BMT) chimaerism. The system is able to detect the DNA equivalent of a single male cell in a background of 10(5) female cells. For clinical applications it has the distinct advantage that the polymorphic nature of the PCR product allows the checking of the genuineness of a positive PCR signal by reference to its allelic type. This extra degree of precision enhances the accuracy of Y-PCR for clinical diagnosis.

Alleles↗
PubMed1994

Oligotyping of HLA-A2, -A3, and -B44 subtypes. Detection of subtype incompatibilities between patients and their serologically matched unrelated bone marrow donors.

We have set up a simple PCR-SSO oligotyping procedure that is able to discriminate ten HLA-A2 (2 PCR/11 probes), two HLA-A3 (1 PCR/1 probe), and two HLA-B44 subtypes (1 PCR/2 probes). The frequency of these subtypes has been determined in a large panel of local blood donors and leukemic patients in combination with their unrelated potential donors. A*0201 and A*0301 were the predominant subtypes (> 95%) for A2 and A3, respectively. B*4402 occurred twice as frequently as B*4403. A2 and B44 subtype mismatches were analyzed in a group of 30 patients and their 116 unrelated potential donors who were matched serologically (low-stringency matching: AB without splits, DR1-10). For seven patients (23%) at least one A2- or B44-subtype-mismatched donor was found. For two of these patients (7%), the subtype-mismatched donor would have been considered as compatible on the basis of high stringency matching (AB splits, DRB1 subtypes, DRB3/B5). For one patient of Mediterranean origin, all five donors recruited from a north European registry (matched with high stringency) appeared to be subtype incompatible (A*0201/A*0205). The rather low percentage of A2- and B4-subtype mismatches in DRB1/B3/B5 matched combinations confirms the significance of linkage disequilibria of HLA antigens. Because unrelated donor selection is done through international registries, however, class I subtyping might be necessary when individuals originate from different geographic areas.

Base Sequence↗
PubMed1994

HLA-DRB1 matched kidneys are preferentially HLA-A and -B compatible and survive longer.

HLA-DR matching was analysed in 111 cadaveric donors and 156 patients who underwent kidney transplantation. We compared the results of conventional DR serology with sequence specific oligonucleotide typing performed on PCR-amplified DRB1 exon 2 DNA. We found discrepancies between serology and DNA typing in 10.1% when the broad antigen specificities DR1-10 were considered. The graft survival probability at 2.5 years between HLA-DR matched versus mismatched transplants was not different (0.87 vs 0.83) when matching was based on serology. However, a significant graft survival difference (0.95 vs 0.82) was found when matching was based on oligotyping for DRB1 (including all subtypes). Furthermore, a better matching for HLA-A and -B was found in the DRB1 matched group. Therefore, precise matching at one particular locus (as shown here for the DRB1 locus) significantly increases the chance to be matched at further MHC loci. The further development of high-resolution typing techniques for most or all HLA-A, -B, -C, -DR, -DQ, -DP antigens may in the future allow more precise definitions of clinically important mismatches helping to develop rational matching strategies.

Graft Survival↗
PubMed1994

HLA-DPB1 DNA polymorphism in the Swiss population: linkage disequilibrium with other HLA loci and population genetic affinities.

Allelic diversity at the HLA-DPB1 locus was determined by PCR-oligotyping in a sample of 125 healthy Swiss individuals. A total of 17 alleles were detected among which four main alleles (DPB1*0401, *0201, *0301, *0402) reached a cumulative frequency of 74.8%. HLA-A and -B (by serology) and HLA-DRB1 (by oligotyping) allelic polymorphisms were analysed also. HLA-B and HLA-DRB1 loci were highly polymorphic with 25 and 28 alleles respectively and similar heterozygosity levels of 0.93 and 0.92. These two loci were found to be more polymorphic than expected under neutrality, while lower heterozygosity levels were found for HLA-A (0.87) and DPB1 (0.81) loci. This paper presents also a global comparison of DPB1 allelic frequencies among 15 populations from four continents. As opposed to the DRB1 locus, overall DPB1 is shown to have a lower level of polymorphism and may be considered as neutral in all tested populations. DPB1 genetic diversity is correlated significantly with geography also, as found previously for DRB1. Two- and four-locus haplotype frequencies were determined and the significance of their linkage disequilibrium tested by an original non-parametric method. A significant positive linkage disequilibrium was found for 11 A-B, 16 B-DRB1, 7 DRB1-DPB1 and 3 A-B-DRB1-DPB1 haplotypes. The overall linkage disequilibrium between DRB1 and DPB1 was much lower than expected from the physical distance and lower than for A-B and B-DRB1 pairs. The implications of these results for bone marrow transplantation and for the evolution of HLA loci are discussed.

Alleles↗
PubMed1994

Relation between the resolution of HLA-typing and the chance of finding an unrelated bone marrow donor.

The chance of finding an unrelated bone marrow donor depends on the size of the donor registry, the frequency of the patient's HLA phenotype and the degree of histoincompatibility considered acceptable. We have studied 60 unrelated bone marrow donor searches and the probability of finding a donor when increasing HLA-compatibility requirements were applied. For 21 (35%) of the patients no donor could be identified who was (serologically) matched for all six ABDR antigens. For the remaining 39 (65%), a median of two (range 1-20) blood samples from serologically-matched potential donors was obtained for further analysis. Eighteen (30%) patients appeared to be mismatched with all the pre-selected donors because of DR (sub-)type mismatches detected by oligotyping. A further 7 (12%) patients did not have an MLC and/or cytotoxic T lymphocyte precursor (CTLp) negative donor. Thus, a 'perfectly matched' donor was found for 11 (18%) patients. To find a suitable donor for more patients we propose that many or all the potential donors identified in the various registries for a particular patient are simultaneously evaluated as many of the serologically ABDR-matched donors will appear to be incompatible after high resolution HLA-typing. This strategy will not only allow selection of the best matched donor more rapidly but the consequent use of high resolution typing might also lead to the definition of a certain number of acceptable mismatches.

Bone Marrow Transplantation↗
PubMed1993

Characterization of mixed chimerism in patients with chronic myeloid leukemia transplanted with T-cell-depleted bone marrow: involvement of different hematologic lineages before and after relapse.

We have characterized mixed chimerism (MC) in five patients with chronic myeloid leukemia (CML) who received transplants with T-cell-depleted bone marrow (BM) and who relapsed within 4 years after transplantation. To study the possible relation of MC with relapse, we purified different populations of leukocytes and analyzed their donor/recipient origin by a method based on polymerase chain reaction amplification of minisatellite DNA regions. Our results show that before relapse, all hematopoietic recipient cells are T cells, whereas monocytes, B, and natural killer (NK) cells are of donor origin. This observation does not appear to be specific for CML as similar results were found in two control patients with acute myeloid leukemia (AML). At the time of (CML) relapse, recipient granulocytes, monocytes, and erythrocytes appeared and progressively replaced the respective lineages of donor origin. No other lineages seemed to be involved as B cells and NK cells remained of donor origin and no significant changes in the number of recipient T cells were detected. In this respect relapse of CML after BM transplantation (BMT) seems not to be very different from the primary disease in chronic phase before transplantation. Furthermore, we conclude that after BMT, an association between mixed chimerism before relapse and the (CML) relapse does exist because both phenomena are consequences of T-cell depletion of the BM graft. However, this correlation might well be indirect as the MC caused by the recipient T cells appears to be independent of the one caused by the recurrent disease.

Adult↗