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V Lepage

Publications and source records attributed to V Lepage.

16 recordsLinked to original sources
PubMed1992

Dose effect of cis- and trans-encoded HLA-DQ alpha beta heterodimers in IDDM susceptibility.

Insulin-dependent diabetes mellitus (IDDM) in whites is strongly associated with particular HLA-DQ alpha beta heterodimers composed of a DQ alpha chain with an arginine at residue 52 (Arg52+) combined to a DQ beta chain lacking an aspartic acid at residue 57 (Asp57-). With the aim of confirming this association, clarifying which heterodimers account for the highest risk of IDDM and explaining the excess risk of DR3-DQw2/DR4-DQw8, 115 unrelated white IDDM patients and 108 unrelated healthy nondiabetic control subjects were studied. With polymerase chain reaction and sequence-specific oligonucleotide probes, both patients and control subjects were typed for their HLA-DQA1 and DQB1 alleles and their DQA1-DQB1 haplotype and genotype frequencies were compared. Four major findings emerged from our analysis. 1) Arg52+ DQ alpha/Asp57- DQ beta heterodimers, formed in cis and/or in trans, are strongly associated with susceptibility to IDDM; 97% of patients and 46% of control subjects had at least one such susceptibility heterodimer (relative risk [RR] 32, confidence interval [Cl] 14.25-71.86, P less than 10(-7). 2) The degree of disease susceptibility depends on the number of such DQ heterodimers that a subject can express according to his or her DQA1-DQB1 genotype. The highest RR was observed in patients with four susceptibility DQ heterodimers (RR 41, Cl 17.05-95.9). 3) Only part of the susceptibility DQ heterodimers were significantly increased in patients, conferring IDDM susceptibility of different strength. The strongest association was with the DQA1*0501-DQB1*0302 combination formed in trans position (RR 35.2, CI 12.88-96.78, P less than 10(-7).(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1978

Some chronic lymphocytic leukemia cells bearing surface immunoglobulins share determinants with T cells.

One set of antigens is common to some chronic lymphocytic leukemia (CLL) cells bearing surface immunoglobulins (Ig) and normal T cells. Proliferating cells from thirty-eight patients were studied with four antisera recognizing normal human T but not B cells. These antisera were raised in rabbits against (a) Sezary cells, (b) blood lymphocytes from a patient with sex-linked agammaglobulinemia, (c) T lymphoblasts and (d) thymus cells. In four CLL cases, the cells expressed the receptor for sheep erythrocytes and lacked surface Ig. Cells from thirty-four CLL cases bore monoclonal surface Ig and did not bind sheep erythrocytes. Twelve out of these thirty-four cases of CLL had cells which were lysed by one or, more frequently, by the four anti-human T cell xenoantisera. By absorption experiments, one set of at least three antigens common to the cells of some of these CLL and T cells was defined. Depending on the patient, the cells can either carry one, some or all of the antigens of this set. However, it was also demonstrated by absorption that these cells lacked antigens particular to the T cell lineage, while the cells from T CLL cases carried both sets of antigens.

Animals↗
PubMed1978

Anti-B cell lymphocytotoxic antibodies in kidney transplant recipients.

Serial serum samples from 47 renal allotransplant recipients were screened for antiperipheral blood lymphocyte, anti-B cell, and anti-Daudi cell line antibodies. Various associations of these antibodies were observed in 28 patients. Anti-Daudi did not correlate with graft survival, whereas anti-B, although they were often associated with anti-peripheral blood lymphocyte antibodies, showed the strongest correlation with chronic rejection (P = 0.00002). However anti-B cytotoxicity preceded or was concurrent with the onset of chronic rejection in only 53% of the cases. Antibodies were absent in six of nine patients with irreversible acute rejection, but they usually appeared after transplant nephrectomy. These findings suggest that anti-B cell antibodies may play a role in the rejection process. In 15 of 17 recipients (88%), anti-B cell antibodies occurred during the first trimester after transplantation. These patients showed 20% 1-year graft survival compared with 68% in those without antibodies at that time (P less than 0.005).

Antibodies↗
PubMed1978

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.

Epitopes↗
PubMed1977

[The Ly-Li system, a new locus of the HLA complex].

Antibodies raised through immunization of volunteers not differing for serologically defined HLA-A, B and C antigens enabled us to define since 1975 a new antigenic system controlled by the HLA complex. These new allo-antigens, designated Ly-Li, are expressed on B lymphocytes but are absent from T lymphocytes, platelets, erythrocytes and fibroblasts. Multiple alleles belong to the Ly-Li differentiation antigen system. The gene frequencies of three alleles thus far detected are 0.1558 for Li2; 0.1867 for Li3 and 0.122 for Li4. Like in the serologically defined HLA antigen systems, "inclusions" were observed also in Ly-Li system, suggesting the existence of private and public specificities. Among 48 families, 23 were informative in showing that the Ly-Li locus segregated with the HLA complex. Data on three families with recombinant haplotypes between HLA-B and D, and between Bf and HLA-D, indicated that the Ly-Li locus was near HLA-D (possibly identical with HLA-D). Anti-Ly-Li antibodies inhibited cellular proliferation in mixed leucocyte culture (MLC) primarily when directed against the antigens of stimulator cells. There was a good correlation between Ly-Li and HLA-D alleles, particularly between Li2 and DW5 (r = 0.70). Usually, HLA-D specificities were "included" in the related Ly-Li specificities, but not vice-versa. In contrast, there was a higher correlation between Ly-Li specificities and those detected by the PLT (primed lymphocyte test). The Ly-Li system seems to be of great importance for the functional characterization of lymphocyte subpopulations, for the selection of the best donor in organ transplantation, and for the investigation of susceptibility genes in diseases associated with HLA-D.

Alleles↗
PubMed1976

A "natural" anti-HLA-A2 antibody reacting with homozygous cells.

In the serum of a young normal male, never transfused, a cold cytotoxic IgM antibody was found reacting exclusively with A2 homozygous cells on a French panel, as shown by population and family studies. This antibody needs about two to five times more lymphocytes or platelets to be absorbed than an immune anti-A2 of the same titre. The antigen recognized by this antibody seems to be covered by the same molecule as HLA-A2, according to redistribution experiments.

Adult↗