Biomedical subjects
Publications and source records attributed to J Hors.
A detailed gene marker study was performed on a partial 6p trisomic child resulting from a balanced maternal translocation t (2;6) (p 2505; p2105). HLA typing and mixed lymphocyte reaction showed that the breakpoint on chromosome 6 was located within the HLA gene cluster, allowing an accurate location of the D determinants. Localization of the P blood group locus within the region 6 p 2105 to 6 p ter was excluded.
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.
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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.
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HLA-A and HLA-B markers have been determined in fibroblasts grown from tissues of triploid conceptuses and have been tested in the parents. Informative data on the origin of triploidy were obtained in eight cases: diandry I or dispermy in 4 cases, diandry II or dispermy in 2, digyny I or II in 2. This confirms that triploidy involved more frequently two sets of paternal chromosomes.
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A total of 126 normal, unrelated individuals from northern central and southern Vietnam have been typed for 32 alleles of the A and B loci, including B HS. The gene, haplotype frequencies and delta values obtained are compared with those of four other Mongoloid populations. The gene frequencies were similar to those found in a Chinese (Cantonese) population.
Forty-eight unrelated patients with idiopathic hemochromatosis were found to have a significantly higher frequency of three HLA antigens (A3, B7 and B14) than 591 healthy controls. A significant association between HLA haplotypes and disease segregations was demonstrated in 14 family studies. A recessive inheritance of a strongly A3-linked disease gene responsible for abnormal iron stores in the heterozygote state is postulated. The lod score value (4.415 for theta = 0.025) is compatible with this hypothesis. However, the excess of HLA-identical pairs of affected sibs does not exclude the possibility of a pseudo-recessiveness due to two codominant genes both HLA-linked. For the first time, a means of screening for high risk subjects is available and therefore offers the possibility of a preventive approach.
In 94 children suffering from cystic fibrosis, no abnormal frequencies of HLA markers of the A and B locus were observed in comparison with the distribution of these antigens in control series. Furthermore, the HLA genotypes of seven pairs of diseased sibs are incompatible with the hypothesis of a closed linkage between CF--an autosomal recessive transmitted disease--and HLA.
Fourteen selected families containing two or more subjects suffering from idiopathic hemochromatosis and 34 unrelated cases have been studied for their HLA markers. A 3 was present in 75% of the unrelated cases vs 26% in the normal population (p less than 10(-8)). The frequencies of B 7 (38% vs 19%) and B 14 (23% vs 9%) were also increased (p lessthan 0,05). Inevitably, in most cases both antigens in the B locus were associated with A 3. Seven of nine affected sib pairs shared both HLA haplotypes, while two shared only one. Significant association between HLA haplotypes and diseases segregation has been demonstrated in family studies. These facts are consistent with the recessive inheritance of a strongly A 3 linked "disease" gene responsible for abnormal iron stores in the heterozygote state. This hypothesis would account for 64% of our present cases. Most of discordances (26%) were females who are physiologically protected, or children under 17 who might later develop the disease. The remaining 10% of disordant cases could be explained by crossing-over between "disease" gene and HLA loci or by an heterogeneity of the disease. This provides a method for screening for high risk subjects and perhaps an opportunity for anticipatory prevention.
The study deals with a family of 22 members spreading over four generations; 14 members suffer from hereditary angio-neurotic edema; all of them have been typed for 30 antigens of the A and B loci in the HLA System and for ABO and Rhesus erythrocyte markers. There is no connection between the disease and any of the markers considered. As for the HLA system, there should be at least 7 chromosomic recombinants to account for the relationship with one of the haplotypes involved.
HLA phenotypes of 13 patients surviving in lasting first remission over 6 years after BCG immunotherapy for acute childhood lymphoblastic leukaemia (ALL) were compared to phenotypes of normal subjects and of surviving ALL patients treated exclusively with chemotherapy. Among the BCG-treated patients, the frequency of the antigen HLA-BW 17 was 46.1% vs 7.3% in healthy controls (p less than 0.001) and the frequency of the antigen HLA-AW 33 was 30.8% vs 1.2% (p less than 0.001). 9 patients possessed at least one of these two antigens (69.2% vs 8% in controls p less than 0.001). Phenotypes of the chemotherapy-treated patients did not differ significantly from controls. These results suggest the existence in humans of HLA-linked genes which are involved in the response to BCG immunotherapy in ALL.
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Thirty-one unrelated patients, 15-52 years old, were typed by microlymphocytotoxicity for 27 alleles of the HLA system. In addition, 12 families including 1 or more patient were also analysed. This criteria for diagnosis were those of Sohar et all. (Am. Intern. Med., 1967, 43, 227-253). All patients were of Israelite-Sephardin origin except two (Armenian and French); they were from North-Africa (Tunisia, Morocco and Algeria) and Israël. The results were compared to the antigen frequencies of 3 reference normal populations. The frequencies of the studied alleles do not differ from those of controls, except for HL-A28 and B14 slightly increased when compared to the normal frequencies. The study of 7 families with at least two sibs suffering from FMF shows a random distribution of the genotypes : 2 HLA identical, 6 different and 10 haploidentical diseased sibs. This distribution differs significantly (p less than 0.01) from that expected in the case of a recessive inheritance. These data do not support the hypothesis of a linkage between genes controlling FMF and HLA genes.
The HLA typing (loci A and B) of a series of fifteen psychotic children has shown an increase of the frequency of both HLA-A9 and B5 antigens. These preliminary data and previous biochemical findings in psychotic patients lead the authors to postulate the hypothesis of a qualitative or quantitative anomaly of the superoxide dismutase (SOD-2), the gene of which is situated on the same chromosome (sixth) as the HLA complex.