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Biomedical subjects

E Ohayon

Publications and source records attributed to E Ohayon.

At least 37 records · Page 2Linked to original sources
PubMed1992

[Study of CD45 isoforms on T CD8 lymphocytes, in the peripheral blood and the graft in patients after kidney transplantation].

We report characterization of CD45 isoforms expressed by CD8+ lymphocytes in peripheral blood and in the graft of 40 kidney transplanted patients who underwent kidney biopsy on the basis of clinical signs suggesting rejection. Standard histological examination of the biopsy fragments and three-color cytofluorimetric analysis of lymphocytes extracted from the same fragments by mechanical and enzymatic treatment were performed simultaneously and compared to the peripheral blood lymphocytes. In 14/40 biopsies where lymphocyte extraction succeeded, the predominant subset was CD8 (CD4/CD8 mean ratio was 0.53). Almost all CD8+ cells were activated: among these CD8+ cells, 55 percent were HLA-DR+, and 68 percent CD45RO+, i.e. of a memory cell type with cytotoxic activity. This situation resembles the in vitro observation made during mitogenic stimulation of lymphocytes by phytohemagglutinin, OKT3 or CML ("culture mixte lymphocytaire"). Beside their evident interest for the diagnosis, these data could be useful for our understanding of the physiopathology of the rejection crisis.

Biopsy, Needle↗
PubMed1992

[Optimization of renal transplantation].

In 1990, 1,949 renal transplantations were performed in France, with a graft survival rate of 89% at one year and 70% at five years. To improve on these results it would be necessary to pursue a dynamic policy in all fields of transplantation: in view of the ever growing number of patients on the transplantation list, more kidneys should be collected; hyperimmunized recipients should undergo reinforced exchanges to have compatible kidneys; immunosuppression must be optimized: just a using cyclosporin and monoclonal antibodies has resulted in a significant advance, so should the discovery of new drugs, such as FK 506, or of more specific monoclonal antibodies, be a source of progress; the complications of immunosuppression must be controlled: prevention protocols and antiviral treatments have considerably reduced the incidence of viral infections. The emergence of malignant tumours directly related to the degree of immunosuppression can be prevented by a rational use of immunosuppressants and by systematic detection. All these advances make it possible to extend the indications of renal transplantation to subjects at risk, notably patients more than 60 years old, and diabetic patients who can successfully benefit from a dual kidney-pancreas transplantation.

France↗
PubMed1992

Multifactorial analysis of the outcome of 6430 cadaver kidney grafts.

A total of 6430 cadaver kidney grafts performed within the network of France-Transplant between 1 January 1978 and 1 January 1989 were analyzed. Each case was examined comprehensively in regard to 12 variables. A multifactorial analysis (Cox regression) was used to determine the degree of association between each covariate and the outcome of the graft. The results were evaluated by calculating relative risks of graft failure for each variable. A total of seven covariates appeared to influence graft survival significantly: the period of transplantation (P = 10(-8)), retransplantations (P = 0.003), age and sex of the donor (P = 0.003 and 0.009 respectively), duration of pretransplant dialysis (P = 0.03), pretransplant sensitization to HLA antigens (P = 0.05), and matching for HLA-A, -B, and -DR loci (P = 0.03). This last parameter has previously been reported as influencing the outcome of the graft in seven out of eight international studies carried out using similar methodology.

Adolescent↗
PubMed1992

New polymorphic HLA-DR epitopes recognized by three monoclonal antibodies produced against DR103 transfected L cells.

Production of monoclonal antibodies directed against polymorphic epitopes of HLA class II molecules using whole human cells as immunogen has often proved ineffective, because most of the antibodies produced are directed against non-MHC human cell surface molecules. One approach to overcome this problem is the use of transfected mouse L cells expressing a single HLA class II allele as immunogen. By immunizing C3H mice with DR103-transfected L cells, we obtained 3 mAb, OHA TM901, OHA TM902, and OHA TM903, that recognize different polymorphic epitopes of the HLA-DR molecule. The molecular specificities of the 3 mAb were determined on a large panel of B-lymphoblastoid cell lines (B-LCL), peripheral blood cells and HLA class II transfectants from the XIth International Histocompatibility Workshop. Interestingly, the 3 polymorphic mAb detect new HLA-DR epitopes shared by several specificities: OHA TM901 reacts with DR1 (DR101, DR103), DR9 (DR901) and DR10 (DR1001) molecules; OHA TM902 recognizes the same molecules but also DR8 (DR801, 802, 803); OHA TM903 reacts with all DR types except DR3 (DR301, 302), DR7 (DR701, 702) and DR52. Surprisingly, OHA TM901 reacts with DR9 transfectants and B-LCL but not with DR9 peripheral blood lymphocytes. Biochemical analyses indicate that the 3 mAb immunoprecipitate HLA-DR products and react in western blots with DR alpha/beta-dimer but not with free alpha- or beta-chains. This study shows that transfected L cells are very useful tools for the production and the fine characterization of mAb recognizing polymorphic epitopes of HLA class II molecules.

Animals↗
PubMed1992

A likelihood approach to HLA serology.

A likelihood approach to HLA serology has been developed in which the aim is not to define a recognition set for a serum but to describe the serum's ability to react with each and every antigen in the test cells, this ability being quantified in terms of the probability of a positive reaction. For a given set of probabilities, one for each antigen, it is possible to derive the probability of the observed set of reactions (the likelihood of the set of probabilities). The maximum possible value of the likelihood for any possible combination of the probability set can then be sought, but this requires a maximization of likelihood with respect to 60-100 independent parameters. Theoretical considerations of the shape of the likelihood surface prove that, in this particular case, this is a feasible proposition. This approach allows the recognition of three groups of antigens: those for which there is considerable evidence of a specificity, those for which there is either no specificity or a very weak specificity, and those for which there is insufficient evidence on which to base a conclusion. The existence of a specificity can be tested using a log likelihood ratio as a statistic, but the usual assumption of a chi 2 distribution of this statistic cannot automatically be made in this situation. Therefore, the distribution is estimated by simulation. A serologist using this approach would receive considerably more information as to the serum's reaction patterns and valid statistics for the existence, or not, of a specificity.

HLA Antigens↗
PubMed1991

Computer-assisted kinetic assay for quantification of total complement activity.

Using apparatus available in any laboratory we developed a semiautomated kinetic technique for complement activity assay. Hemolysis of sensitized red blood cells is performed in the thermostated microflow cell of a spectrophotometer connected to a computer. The computer controls, displays on the screen, and analyzes all the different phases of the assay. After definition of optimal operating conditions, we compared the results obtained by this technique and by Kabat and Mayer's. On 221 patients' sera the regression coefficient was 0.94. The values for samples deficient in one fraction or after in vitro activation were very similar. The coefficient of variation was close to 1% for within series studies and better than 3% between series. This technique is very easy to perform even in a routine nonspecialized laboratory and up to 30-40 sample/h can be tested.

Antibodies↗
PubMed1991

[HLA-B and psoriatic rheumatism. Study of 193 cases].

Study of the HLA-B grouping of 193 patients with psoriatic arthropathy (PA), compared with that of a control series consisting of 2,706 healthy subjects representative of the French population, revealed a statistically significant link between PA and antigens B27, B17 and B16. In contrast to reported findings of earlier studies, the authors found no link between an HLA-B antigen and any particular topographical or anatomical form of PA. Antigen B27 was not statistically significantly linked with axial forms of PA nor did it protect against peripheral forms. There were neither more cases of peripheral involvement nor less of axial involvement among non-B27 PA patients. The only statistically significant link which could be shown was that between antigen B27 and sacroiliac involvement in recent PA, present for less than 10 years. The authors conclude that in 60 per cent of cases, PA is associated with a particular antigen: B16, B17 or B27. Involvement of the sacroiliac joints is more common in cases of B27 PA and above all occurs earlier than in others. Regardless of its HLA group, PA as it progresses shows an increasingly clear mixture of spinal, peripheral and sacroiliac lesions, which forms the basis of the originality of this condition.

Adolescent↗
PubMed1990

Analysis of HLA-DP in HLA-DR/GLO recombinant families and in the population of south-western France.

The existing estimates of the recombination fraction between DR and DP are quite variable and often based on anecdotal observations. We have estimated the DR/DP crossover frequency on the basis of families typed for HLA markers and GLO. The frequency of DR/GLO crossing over was 8.7% (23/264 informative meioses), maternal recombinations being about twice as frequent as paternal ones. Of 17 DR/GLO recombinant families typed for DPw1-6, DP was informative in 11 (13 recombinations) but only one of these gave rise to a DR/DP crossover. According to these data the DR/DP recombination fraction is below 1%, in contrast to some earlier published materials. HLA-DR/DP haplotypic associations on 127 informative Caucasoid haplotypes have been evaluated. In agreement with previous studies, DR3 was positively associated with DPw1 and, in addition, DR7 was found to be positively associated with DP-blank (not DPw1-6). The rare DPw6 allele is possibly associated with the DR4, Dw14 allele. The DR-DP haplotype profiles suggest other associations which might become significant if larger materials are tested. The frequency of DP alleles in a random material (N = 201) was found to be in accordance with most of the previously published frequences on European Caucasoids with DPw4 as the predominating frequency (gene frequency 40%) and a blank frequency of 27%.

Alleles↗
PubMed1988

The susceptibility to insulin-dependent diabetes mellitus is associated with C4 allotypes independently of the association with HLA-DQ alleles in HLA-DR3,4 heterozygotes.

In the genetically homogeneous Danish population, 27 HLA-DR3,4 heterozygous patients with insulin-dependent diabetes mellitus (IDDM) and 19 DR3,4 heterozygous controls without family history of IDDM were investigated for HLA-region markers and Gm and Km immunoglobulin allotypes. The aim was to define susceptibility factors for IDDM development other than HLA-DR using a number of techniques: lymphocytotoxicity (HLA-DR and DQ antigens), cellular methods (Dw and DP typing), restriction fragment length polymorphism (DQ alleles), electrophoresis and immunofixation (BF and C4 allotypes), and passive hemagglutination inhibition (Gm and Km immunoglobulin allotypes). The complement allotype C4A3 and the HLA-DQw8 (DQw3.2) antigen were found in all of the patients, whereas this was the case for only 8 of the 19 controls (P = 6 x 10(-6)): five lacked C4A3, five others lacked DQw8, and one of the controls lacked both of these factors. Fourteen of the patients had the complement allotype C4B3 versus three of the controls (P = 0.01). Previously reported family studies suggest that these alleles are part of the following haplotype: B15, BFS, C4A3, C4B3, DR4, Dw4, DQw8, and these factors were found together in ten of the patients versus one of the controls (P = 0.01). The markers usually associated with DR3 did not show significant differences between IDDM patients and controls, and the non-HLA markers studied showed no significant deviation from what was expected. In addition to the susceptibility factor DQw8, the study suggests the existence of susceptibility genes for IDDM near the complement C4 genes on DR4-carrying haplotypes.(ABSTRACT TRUNCATED AT 250 WORDS)

Complement C4↗
PubMed1988

No evidence for sex ratio distortion in relation with feto-maternal HLA-DR compatibility.

Two separate studies have shown a distortion in the sex ratio of first born children from HLA-DR compatible parents (Ober et al. 1985, Radvany et al. 1987). Kilpatrick (1987) was unable to confirm this distortion on an independent family data set. The question of the HLA-DR related sex ratio distortion still remained open. In the data set, "Provinces Françaises" families from 15 French provinces and Quebec were tested for a number of genetic markers including HLA-DR. In 1304 of these families, the HLA-DR results and family structure information were sufficient to allow the testing of this hypothesis. There were 2265 male and 2156 female children (overall sex ratio: 1.05); 1307 males and 1237 females were HLA-DR typed. In this group, the sex ratios are little different from those in the overall set, except for the firstborns which exhibit an apparent increase in the sex ratio. When dividing the sample between children fully HLA-DR compatible with their mother and those incompatible (i.e. having one antigen not present in the mother), the sex ratios in the two groups are little different whatever the birth order. This analysis has failed to observe any significant distortion in the sex ratio related to fetomaternal compatibility in agreement with the study of Kilpatrick. We conclude that, if such a distortion exists, it must be small.

Female↗
PubMed1988

[Correlation between the IgG oligoclonal pattern and the benign nature of monoclonal abnormalities in the aged subject].

The presence of an IgG oligoclonal pattern was investigated by isoelectric focusing and immuno detection in 151 individuals over 60 years of age. One hundred are individuals with no detectable monoclonal anomaly and among them, 22 exhibit an oligoclonal pattern. The others are 27 patients with a benign and 24 with a malign monoclonal dysglobulinemia, including respectively 9 and 2 oligoclonal patterns. In all groups the oligoclonal pattern is always found among the oldest individuals. The small association found between this special distribution of the IgG and the benign monoclonal dysglobulinemia seems to be most probably in favour of aging. The IgG oligoclonal distribution associated to a monoclonal component would not be a discriminating argument for malignant or benign monoclonal proliferation diagnosis.

Age Factors↗
PubMed1986

A new HLA-D specificity associated with DR blank: D-BON.

Since 1980, a DR blank specificity undefined by serology but known to segregate in families linked to DQw1 has been recognized. We describe a Caucasoid family, BON... where 4 among 8 children are homozygous for such a specificity; their cells can be used as homozygous typing cells and the specificity defined is provisionally called D-BON. There is no known consanguinity in this family. The homozygous D-BON cells carry DR molecules as shown by their reactivity with monomorphic anti-DR monoclonal antibodies. In a random family material consisting of 210 haplotypes, the gene frequency of D-BON is between 1 and 2%, which corresponds to about 40% of the DR blank frequency. The D-BON specificity seems associated with DQw1 and also with B35 and C4B2.

Adult↗
PubMed1986

[HLA and Bf in idiopathic nephrotic syndrome in children: differences between corticosensitive and corticoresistant forms].

An association between HLA-DR7 and the steroid sensitive idiopathic nephrotic syndrome in the children has already been reported. Immunogenetic data in the less frequent steroid resistant form of this disease have never been published. In this study, we analyse HLA-A, B and DR typing in 99 cases of nephrotic children divided in 72 with the steroid sensitive (SS) form and 27 with the steroid resistant (SR) syndrome, in comparison with those of 207 healthy controls; Bf allotypes were determined in 53 of the patients. The results show the increased frequency of DR7 in the SS syndrome (75% vs 30%, RR = 6.9, pc less than 10(-6), while the SR one is more associated to DR3 (52% vs 27%, RR = 3, p less than 0.004). In the SS patients, atopy is associated to DR7 (p less than 0.001), which is not the case in the SR group. Furthermore, a high relative risk is associated to the phenotype DR3/DR7 (30% vs 4%; RR = 9.3; pc less than 0.0004), for the SR disease; besides, this phenotype is associated to an early onset of the disease and to lesions of focal sclerosis. Thus a heterozygous effect in the SR form of idiopathic nephrotic syndrome of children has been demonstrated; the steroid sensitive and the steroid resistant forms of the disease seem to have different immunogenetic components.

Adrenal Cortex Hormones↗
PubMed1985

Recombination between HLA-A and C and between HLA-B and complement locus C4 in the same individual.

In a French family with 2 parents and 5 children a crossing over was found in the HLA region on both of the parental haplotypes of one of the children. The following markers were studied: HLA-A, B, C,DR, DQ(MB), DP(SB), complement allotypes C4 and Bf and glyoxalase I polymorphism. In the third child, the paternal haplotype had a recombination between HLA-A and HLA-C and the maternal haplotype a recombination between HLA-B and complement locus C4. Mixed lymphocyte cultures confirmed the serological findings and non-HLA markers (blood groups and immunoglobulin allotypes) showed no evidence of extrapaternity. The family also demonstrates a probable duplication of the C4B1 gene in one of the paternal haplotypes.

Complement C4↗
PubMed1985

Platelet absorption on the test tray (PATT): a rapid method for the screening of HLA class II antibodies using the two-colour fluorescence method.

Several strategies have been proposed for the screening of alloantisera towards HLA class II antigens. Most often the absorption of the sera with platelets is required in order to remove their anti-HLA-A, B, C activity. We have developed a simple micromethod for platelet absorption of sera: platelet absorption on the test tray (PATT); 0.5 microliter of platelet suspension is incubated with 0.5 microliter of the serum to be absorbed in the same tray which is subsequently used for the microlymphocytotoxicity by the two-colour fluorescence method. This technique is proved to be almost as efficient as classical absorption procedures: out of 44 anti-HLA-A, B sera the T-cell activity is completely removed in 43 by a classical procedure as compared to 41 by PATT; only 8% discrepancies were found among 394 reactions. PATT was then used for anti-B lymphocyte screening in 419 anti-HLA-A, B sera; 4% of the sera remained cytotoxic towards T and B lymphocytes while 35% reacted only with B cells, several of them being DR specific. PATT can also be useful for T/B lymphocyte differential cross-matches before kidney transplantation. The method is now routinely used in our laboratory for anti-HLA class II antibody screening.

Absorption↗