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Biomedical subjects

M Busson

Publications and source records attributed to M Busson.

At least 109 records · Page 6Linked to original sources
PubMed1984

Distribution of HLA-A,B alleles in 13 panels of blood donors in France.

In this study, we analysed 13 samples of the French population--4147 non-related individuals living in Bordeaux, Brest, Caen, Dijon, Limoges, Lyon, Marseille, Nancy, Paris, Poitiers, Rennes, Strasbourg and Toulouse--all of whom were typed for 10 alleles of the HLA-A locus and 16 alleles of the HLA-B locus. The results showed a strong heterogeneity (chi 2 = 675.13 for 324 df, p less than 10(5)). A diagram has been drawn up, showing the matrix of genetic distances obtained thanks to the B2 of Balkrishnan & Sanghvi (1968). This diagram enables us to envisage the hypothesis of 6 homogeneous clusters. A partition of chi 2 was used to test this 6 luster hypothesis: Paris and Caen (p = 0.98); Nancy, Strasbourg (p less than 5%); Rennes, Brest (p less than 1%); Dijon, Lyon, Marseille (p = 0.89); Limoges, Poitiers (p = 0.18); Toulouse, Bordeaux (p less than 10(-5)). The heterogeneity within these clusters represents only 1/43 of the total heterogeneity.

Alleles↗
PubMed1984

Evaluation of recurrence risk in siblings of diabetic children: importance of age and birth order in relation to HLA genotypes.

In order to identify factors other than the HLA-linked susceptibility involved in the risk to the siblings of diabetic children, we compared the age at onset, birth order and HLA genotypes in 23 IDD multiplex (Mx) families and 140 simplex (Sx) families. The results showed a relationship between age and recurrence risk in sibs. Probands (= 1st affected sibs) of Mx families were significantly younger at onset (5.8 +/- 0.8 yr) than probands of Sx families (9.0 +/- 0.4 yr, p less than 0.01). The 2nd affected sibs of Mx families, although affected at an older age (12.4 +/- 1.6 yr), had been significantly younger at the time of the proband's onset, than the siblings who have remained unaffected (6.2 +/- 1.2 vs 11.5 +/- 0.5 yr, p less than 0.01). Probands of Mx families were more often the first born and probands of Sx families, more often came later in the birth order (p less than 0.02). Prevalence of IDD was higher among siblings born after than among those born before the proband (12% vs 4%, p less than 0.002). The HLA haplotype distribution in unaffected siblings deviated from the random assortment in relation to birth order, showing an excess of HLA-identical sibs born before the proband and, inversely, an excess of non-identical sibs born after the proband. The results suggest that age-dependent factors are likely to increase the penetrance of HLA-linked IDD susceptibility. These factors could be related to the environmental insult. However, a genetically determined form of type I diabetes characterized by higher familial penetrance and earlier onset cannot be ruled out.

Age Factors↗
PubMed1983

[Role of transfusions and significance of HLA-A, B and DR compatibility in renal transplants].

The results study of renal allograft performed in the France-Transplant network, shows the beneficial effect of blood transfusions on graft survival; their immuno-suppressive effect allowed the tolerance of the transplant, despite of the presence, at times, of incompatibilities HLA. In this work, we have studied the effect of HLA-A, B, DR incompatibilities in 803 unrelated recipients according to their preimmunized status. In the 303 presensitized patients (by transfusion or transplantation) we show clearly the strong effect of the HLA compatibility and the additive effect of the three loci A, B, DR (94% of graft survival at two years for the best matched v.s. 36% for the worst). In the 500 non responder patients, there is no effect of the compatibility A, B, DR (69% for the best matched v.s. 71% for the worst). Presensitized patients reach currently 50% of the waiting list of dialysed. Cooperative efforts should avoid heavily mismatched transplants in case of preimmunization.

Actuarial Analysis↗
PubMed1983

Analysis of HLA class I genes with restriction endonuclease fragments: implications for polymorphism of the human major histocompatibility complex.

Cellular DNA from HLA-typed individuals was digested with the restriction endonucleases HindIII, EcoRV, and EcoRI. The separated restriction endonuclease fragments were hybridized with a HLA class I cDNA probe by using the Southern transfer technique. Digestion of cellular DNA with HindIII generated 22 restriction endonuclease fragments, 11 of which showed polymorphism for presence or absence in a population sample. With EcoRV, 13 fragments were identified; 6 showed polymorphism. EcoRI generated 11 fragments, of which 1 was polymorphic. Of these 18 polymorphic fragments generated by the three restriction endonucleases, each of 5 was found to be positively associated with one allele of the HLA-A or -B allelic series (HLA-Aw24, -B8, -B15, -Bw35, and -B40). One fragment was positively associated with two HLA-A series alleles (HLA-A1 and -A11). Another fragment was positively associated with five HLA-B series alleles (HLA-B5, -B7, -B14, -Bw16, and -Bw35) and one fragment was positively associated with alleles at two loci (HLA-B14 and -Cw5). The serologically defined allele HLA-Aw24 was associated with two polymorphic fragments, one association showing a positive correlation and the other a negative correlation. Each informative family studied thus far has shown segregation of the restriction fragment with the associated serologically defined allele. The fragments associated with serologically defined alleles occurred in the population sample studied at low or moderate frequencies. The remaining polymorphic fragments occur at high frequency, suggesting that class I genes not serologically detected show less polymorphism than serologically defined class I genes.

Alleles↗
PubMed1983

[Computer analysis of anti-HLA sera: ANASER. Its application in kidney transplantation].

ANASER is a system of 3 computer programs for the analysis of sera from multi-transfused patients, multiparous women and dialysed patients awaiting kidney transplantation, which react against one or more HLA antigens. This system permits: 1) the recognition of one or more HLA specificities in each serum using iterative analyses. 2) The calculations of correlation coefficients among several sera. 3) The drawing of positive serological reactions according to either a given sera or to a given antigen. It can be used for two main purposes: 1) to permit selection of the best sera for HLA typing (positive correlations). 2) To study the preimmunization of dialysed patients awaiting kidney graft. Owing to sequential comparison of the consecutive bleedings from the same individual, they allow the definition of a pattern of anti-HLA immunisation, and in the case of large spectrum antibodies, the specification of antigens not concerned by the antibodies produced (negative correlations). ANASER may help in the choice of the best compatible transplant for hyperimmunized patients, who need a precisely matched organ.

Antibodies↗
PubMed1982

HLA haplotype study of 53 juvenile insulin-dependent diabetic (I.D.D.) families.

R4 heterozygotes was observed. By contrast, the observed frequency of patients homozygous for DR3 or DR4 was not increased, but even slightly decreased. The data support a model of inheritance comprising at least two closely linked specifically "diabetic" loci (most of the time marked by B18, BfF1, DR3 and B15, BfS, DR4) and a non-specifically "diabetic" haplotype favouring auto-immunisation (most of the time marked by B8, BfS, DR3). This model is discussed in the light of the presented data and of those of the literature.

Adolescent↗
PubMed1982

HLA and longevity.

One hundred fifty-five healthy nonagenarians, 45 men and 100 women, all French Caucasians, were phenotyped for alleles of the A, B, C, DR loci of the HLA complex. The observed HLA antigen frequencies were compared to those of a control series of 133 males and 179 females whose ages ranged from 10 to 50 years. When comparing the total young and elderly series, no significant differences were observed with respect to HLA antigen distribution or heterozygosity at any of the loci. When taking sex difference into account, however, an excess of the Cw1 antigen was found in the group of elderly females (p less than 0.001) and an excess of the Cw7 antigen in the group of elderly males (p less than 0.001). Of particular significance was the fact that Cw7 belonged in this instance to a phenotypic combination (and most probably to the corresponding haplotype) A1/Cw7/B8/DR3 which was found significantly increased in male nonagenarians (p less than 0.001). These results support the hypothesis that certain HLA haplotypes are associated with survival advantage.

Adolescent↗
PubMed1981

HLA markers in patients suffering from aplastic anaemia.

135 patients, suffering from aplastic anaemia (AA) and their families were genotyped for HLA. The antigen and haplotype frequencies were compared to an HLA genotyped control panel composed of 209 normal couples and their healthy offsprings, and to another series of 2286 normal individuals. An excess of HLA-A2 was observed in the patients: 61% versus 42% (pc less than 0.001) (relative risk: 2) and versus 48.5% (p less than 0.01) in two control series, respectively. When considering the HLA-A, B antigens shared in common by the parents of the AA patients, an excess of HLA-A2 was observed: 32% as compared to 17% shared by normal couples (p less than 0.001). An excess of homozygous HLA-A2 was noted in the AA patients (14%) in comparison to the normal controls (4%) (p less than 0.001). The mechanism of this association is discussed as well as the hypothesis of a gene involved in haematopoiesis which might interact within the HLA-A region.

Anemia, Aplastic↗
PubMed1980

HLA genotype studies in juvenile insulin-dependent diabetes.

HLA genotypes were ascertained in 53 French Caucasian families, comprising 68 juvenile onset insulin-dependent diabetic siblings. Among the 49 alleles detected at different loci in the HLA complex (A, C, B, Bf, DR) 4 appeared to occur at a significantly higher frequency among the 53 index cases than in a control series of 116 healthy individuals: HLA-B18 (p < 10(-3)), DRw3, DRw4 and BfF1 (p < 10(-6)). The excess of HLA identical affected siblings confirms genotype disequilibrium and supports the hypothesis of an HLA-linked gene(s) conferring susceptibility. There was no increase of homozygosity for HLA DRw3 and DRw4 whereas there was a marked excess heterozygosity for HLA DRw3/DRw4 in diabetic patients (32% versus 0% in the control series, p < 0.001). These data provide evidence for the existence of two cooperating genes, linked to each of the HLA DR alleles.

Alleles↗
PubMed1979

Is the strength of single HLA antigen mismatch variable in kidney transplant survival?

The survival rate among 458 cadaver kidney grafts with "full-house" four HLA-A,B antigens detected in the donor, three being identical to those of the recipient and only one mismatched, was studied specifically in relation to antigen incompatibility. At the A locus, the A3 incompatibility was associated with a lower transplant survival (44% at 2 years) than all of the others, and particularly more than the A11 (80% at 2 years) (P less than 0.003 but without significance after correction multiplying by the number of tested alleles). At the B locus, there was no significant difference in survival rate among the alleles. These results are only preliminary and need confirmation based on longer series permitting possible cross-reactions which exit between donor and recipient antigens to be taken into consideration.

Alleles↗
PubMed1979

A simulation of HLA-DR matching in kidney transplantation.

A simulation of the matching for HLA-DR, B, A loci was achieved by taking into account the practical situation of kidney transplants for 89 donors and 322 potential recipients. A complete HLA-DR identical graft was theoretically possible in 52% of the cases. Conversely, if the identity for B or particularly the identities for both B and A were sought, the necessary pool of recipients would have to be much larger, requiring intense international cooperation.

ABO Blood-Group System↗
PubMed1979

Insulin-dependent diabetes and HLA.

The study of a hundred and fifteen unrelated insulin-dependent diabetes and eight families with at least two insulin-dependent diabetes members made it possible to confirm the higher frequency of HLA-B8 and B18 (p less than 0.001) among patients, producing a RR of 2.24 and 2.47 respectively. The increased B15 frequency did not achieve statistical significance. B18 whose gametic association (delta = 0.0438) was significant only in diabetic patients was often related to Aw19-2 (Aw30 + Aw31). The B8/B18 genotype gave a relative risk (RR = 4.98) which was significantly higher than that of B8, B18 and B15 heterozygotes (1.50, 1.24 and 1.39 respectively). Pairs of diabetic siblings were more frequently HLA identical than would be expected by chance, and distribution of the pairs of affected sibs into the three categories, identical, semi-identical and different, was closer to the recessive model than to the dominant one. The fact that the B8/B18 individuals had a RR slightly higher than the B8 and B18 homozygotes and distinctly higher than the heterozygotes for only one of these genes, favours the hypothesis of two dominant genes, giving the appearance of recessivity. The gene associated with B18 in Southern Europe seems to play the same part as that of the gene associated with B15 in Northern Europe.

Adolescent↗