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

Fifty-three families with at least one IDD patient were genotyped for 5 markers of the HLA complex including Bf and DR. In 8 families one of the parents was also affected and in 12 families more than two children were diseased. In total, 76 patients were genotyped. Their haplotypes were compared with those of 106 unrelated controls (the parents of 53 genotyped families).

• 1) 

  Three haplotypes or segments of them (A2, Cw3, B15, BfS, DR4; Aw30, Cw5, B18, BfF I, DR3; and Al, Cw7, B8, BfS, DR3) were found more frequently in IDD patients.
• 2) 

  Measured by the 6 formula, the association of the postulated IDD susceptibility gene was very strong with the D-end of two of these haplotypes: BfF1, DR3 and BfS, DR4. However, the association was weak with the DR3 of the haplotype Al, Cw7, B8, BfS, DR3.
• 3) 

  An excess of HLA-identical affected siblings was found.
• 4) 

  An excess of DR3/DR4 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, BfFl, 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.     

Image analysis application at immuno-hematology (author's transl)]

Image analysis is an original method for the determination of blood groups and tissue types and for the serology of syphilis. Major advantages are the rapid and specific discrimination of biological particles present in agglutinated or free form, either fluorescent or stained. The reading of the tests is instantaneous and quantitative. The results are expressed immediately and stored with the use of computers. We have studied three micromethods, two for red blood cell grouping and irregular antibodies screening and one for the serology of syphilis, each one being adapted for an automatic system.     

Seventh allele of the HLA-C series (Cve).

Serum VE reacting with 29.8% of French individuals seemed to define the seventh allele of the HLA-C series as shown by serologic and genetic investigations. The gene frequency of Cve is 0.163.     

Qualitative and Quantitative Study of the Antigens and Antibodies of the HL-A System — Automatic Fluorochrome Method

Abstract. It was possible to obtain a successful evaluation of the quantity of HL-A antigens on lymphocytes using a fluorochromatic test with double marking by fluorescine diacetate and ethidium bromide. It was also possible to detect anti-HL-A antibodies, to study their cross-reactions and to perform tissue typing using this automatic, sensitive and repeatable method.     

HLA-A,B,C, Bf and glyoxalase I polymorphisms in a sample of the kabyle population (Algeria)

HLA (A,B and C) gene and haplotype frequencies were determined in 44 Berber families from the Kabyle tribe. The Bf and Olo polymorphisms were also defined and the haplotypes were deduced from these family data. The main association (A1, B8, BfS; A29, B12, GIo²; Aw33, B14, BfS, GIo¹; Cw5, B18, BfF1; A1, Bw17) showed the relationship between the populations from the southwest of Europe, and this population. Another association, A11 and Bw21, was found also in Twareg, which are probably of the same origin.     

A Haplotype Study of HLA Complex with Special Reference to the HLA-DR Series and to Bf. C2 and Glyoxalase I Polymorphisms

Fifty-three French families were typed for alleles at seven loci of the HLA complex (HLA-A, -B, -C, -DR, -Bf, -C2 and -GLO) and 212 haplotypes were demonstrated. Eleven recombinations were observed (two A/B, two A/C, two B/Bf, one Bf/D and four D/GLO). The linkage disequilibrium was calculated not only between two alleles (delta) but between three, four...seven alleles (D). In order to compare the intensity of D values in the various haplotypes, the influence of the differences in gene frequencies was eliminated by the introduction of the standardized Ds (Ds = D/D max). The number of haplotypes in disequilibrium is relatively limited since most of the significant Ds involved about 17 haplotypes. For some haplotypes, the disequilibrium covered the whole distance from A to GLO but the stronger disequilibrium concerns the C to Bf or C to DR segment. Three hypotheses (isolation, admixture of population and selection) concerning the formation and maintenance of the disequilibria are discussed.     

HLA Genotype studies in juvenile insulin-dependent diabetes

Summary 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.     

A Lymphocyte Immunogenetic System, Atri, Associated with the ABO Blood Group and the ABH Secretor System

The antigen Atri can be detected on the lymphocytes of 5.19% of A, ABH secretor individuals. The Atri substance is present in the plasma of the same individuals and can be fixed on group O erythrocytes. It is also found in the saliva of 30 out of 32 A non-secretor individuals. Its existence in the saliva of A secretor individuals, however, cannot be proved due to the presence of both the A and Atri antigens. The A AND Atri antigens have been shown to be distinct on lymphocytes by capping and by blocking of the A sites. The fact that in several families the Atri antigen is not expressed by the parents shows that its expression on lymphocytes requires the intervention of at least one gene in addition to ABO and Se.