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The HLA-DMA gene, along with the HLA-DMB gene, encodes the not classical class II molecule. This molecule catalyzes the class-II-associated invariant-chain peptide (CLIP)-antigen peptide exchange in classical class II molecule peptide-binding groove. As such, the DM heterodimer is an antigen presentation regulator and may be linked to immune system deficiencies such as those observed in autoimmune diseases. The study of DMA gene polymorphism seems be a reasonable approach to provide an answer to this question. Thanks to PCR-derived methods, the relationship between DMA gene polymorphism and rheumatoid arthritis (RA) was demonstrated in the present study. The DMA*0101 allele was observed to confer a significant predisposition to RA while the DMA*0102 allele significantly protected from this disease. Polymorphism experiments with the HLA-DRB1 gene revealed that this relationship between DMA polymorphism and RA is not a consequence of a linkage disequilibrium with the HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore prove to be very useful in the early diagnosis of RA., (Copyright 1999 S. Karger AG, Basel)

The HLA-DM molecule catalyses the CLIP/antigen peptide exchange in the classical class II peptide-binding groove. As such, DM is an antigen presentation regulator and may be linked to autoimmune diseases. Using PCR derived methods, a relationship was revealed between DM gene polymorphism and IDDM, in a Corsican population. The DMA*0101 allele was observed to confer a significant predisposition to this autoimmune disease while the DMA*0102 allele protected significantly. Experiments examining polymorphism of the HLA-DRB1 gene established that these relationships are not a consequence of linkage disequilibrium with HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore be an additional tool for early IDDM diagnosis in the Corsican population.

Unrelated donor searches for 100 Caucasian patients were referred to France Greffe de Moëlle Registry (FGM) from September 1987 (24,600 donors) to December 1993 (71,500 donors, 61% DR typed). After DR typing of HLA-A,B matched donors, unsuccessful searches were extended to other European Registries for 36 patients. Twenty two patients had a donor (FGM: 19, other Registries: 3) selected on: (1) HLA-A,B and DRB,DQB1 split identity; and (2) unidirectional relative response < 5% in MLR performed twice. Estimated probability of finding a compatible donor at 9 months in FGM was 12% (s.e. +/- 4%) and 25% at 2 years (s.e. +/- 6%). This probability was stringently dependent on a phenoidentity to one very common HLA-A,B,DR or B,DR haplotype (25% at 9 months when present, representing 19 of 19 patients with a compatible donor). Without this phenoidentity, the probability was zero per cent (P = 0.0001) in FGM searches and < 4% (n = 1) in extended searches. The MLR test was shown to be insensitive for screening for DPB1 mismatches. Clinical status influenced the probability of finding a compatible donor at one year ranging from 9% +/- 9% for ALL to 23% +/- 8% for CML (NS). Disregarding DPB1 mismatches is the most efficient way of increasing search efficiency.

The study of the genic and antigenic frequencies of the ABO and Rhesus systems amidst a population of 16559 subjects, reveals are very good correlation as regards the various autors. Considering the HLA typing of 481 subjects, one will point out the lowering of the HLA2 antigen.

An investigation of Cad phenotypes in the French population had been carried out in 1973, in four Blood Transfusion Centers (Mulhouse, Nancy, Paris, Versailles), B and O red cells were tested with the Dolichos Biflorus lectin. Out of 78.528 donors, 56 were found to have the Cad antigen on their red cells. The mean frequency was 0,07%. Nevertheless, this frequency varied among the four above mentioned Blood Transfusion Centers: the observed differences were probably due to the preparation procedure of the Dolichos biflorus extract. The family investigation permitted the analysis of four families with at least three Cad individuals. The independence of the Cad system and of Auberger, Gc, Hp, C'3, PGM, Pac and ADA was demonstrated. A quantitative agglutination study on these Cad samples using the Dolichos biflorus lectin,and a selected AB serum showed a high variability of the erythrocyte Cad Strength, even within one family. Most Cad samples were found polyagglutinable when a sensitive technique and selected AB sera were used. All adult sera contained an anti-Cad1 antibody, except Cad1 individuals. Although strong Sda reactivity was always found in Cad red cells, the anti-Cad and anti Sda specificities were not identical: this was demonstrated by the absorption and inhibition tests of anti-Cad and anti-Sda reagents absorption and inhibition tests of anti-Cad and anti-Sda reagents with Sda material. From thf Cad red cells, there was no evidence of the existence of separable anti-A1 and anti-Cad agglutinins in the Dolichos biflorus lectin.

Idiopathic hemochromatosis is an hereditary iron overload. The study of HLA types demonstrated clearly the linkage with HLA system. The preferential correlation established with A3 (72%) but other alleles were linked: B7, B14. HLA alleles were only the markers of hemochromatosis allele (H) and were not implicated in other iron overload. Family studied, defined two linked haplotypes: A3, Cw7, B7, Bw6, BfS, DR2, GLO1 et A3, Cw8, B14, Cw6, BfF, DRw6, GLO2. Demonstration of the recessive mode of inheritance was established by family studies. The affected siblings had the same HLA haplotype that the proband and homozygous or heterozygous expressed state was assessed in siblings. The HLA family types allowed to detect in 147 families 88 potential diseased patients among of them 73% had early blood-drawing.