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Biomedical subjects

R Fauchet

Publications and source records attributed to R Fauchet.

At least 109 records · Page 6Linked to original sources

A common epitope between HLA-B27, -B13 and -B37 alloantigens defined by a monoclonal antibody.

An anti-HLA-B27 monoclonal antibody produced by the hybridoma technique is described. This BD.7 reagent is a cytotoxic IgM antibody. Its reactivity was studied by lymphocytotoxicity tests, indirect immunofluorescence tests and biochemical analysis against an extensive panel of peripheral blood mononuclear cells. All HLA-B27 positive samples, either from normal subjects or from patients with Ankylosing Spondylitis, were recognized by this reagent. Moreover, a cross-reaction was observed with HLA-B13 cells, and a new unexpected reaction with all HLA-B37 cell suspensions. The interest of such a reagent is discussed.

Antibodies, Monoclonal↗

[Immunologic characteristics of repeated spontaneous abortions].

In 28 couples with spontaneous abortions, data of immunological investigations revealed an elevated frequency of HLA DR compatibility and immunological characteristics defining distinct patterns of immune responsiveness. In the half of women with recurrent spontaneous abortion (RSA) we observed a failure to develop a recognition response to paternal inherited fetal antigens expressed by the lack of classical evidence of in vivo allo-immunization such as antipaternal antibodies, and the absence of the inhibitors of cell-mediated immunity found in maternal blood during pregnancy. In few cases, the paternal cells are inefficient to elicit in vitro maternal cell-mediated lympholysis. In most women with a normal pregnancy occurring after spontaneous abortions or prior to RSA, an immune recognition response was evidenced by the presence of antipaternal antibodies and/or blocking factor acting on in vitro cell-mediated lympholysis. These observations support the hypothesis that immunological process could be the cause of some fetal losses of unknown etiology, through a defective or unsuitable maternal immune response.

Abortion, Habitual↗

[Demonstration of new class I antigens in man].

The hypothesis of new class I antigens has been postulated in man, and several antigen systems have been proposed: HT (Gazit), TC (TCA, TCB) (Van Leeuwen). The present study describes a new class I antigenic marker system, expressed selectively on PHA-activated T lymphocytes and on lymphoblastoid B cell lines. These markers correlated at the cellular activation stage, have been called: human activation or HA markers. 7% of the sera from multiparous women present anti-HA antibodies. The definition of class I molecule (dimer 41K - 12K) has been established by a structural analysis of the molecule; the responsible gene, located on the 6th chromosome could be close to the HLA-A gene. The equivalence with the mouse Qa markers is postulated, but remains to be totally demonstrated.

B-Lymphocytes↗

[What has become of preliminary transfusion protocols in kidney transplantation?].

Many studies have demonstrated that pretransplant blood transfusions improved cadaver kidney graft outcome. The nature and the frequency of transfusions-induced lymphocytotoxic antibodies depends of sex, previous pregnancies and kidney grafts, and transfusional patterns. This provoked immunisation is not a hindrance to beneficial effects of transfusions. Numerous reports have investigated the responsible mechanism for this effect. Controversial data concern the optimum number of blood units. In a previous prospective study in patients who received anti-lymphocyte globulins as part of immunosuppressive therapy, we have shown that a multiple transfusions policy does not give better results than only one. Recently, the beneficial effect of transfusions has been questioned, either entirely, or for particular patients according to age, sex, immunosuppressive treatment including cyclosporin or not. This leaded us to reassess benefits of transfusions.

Blood Transfusion↗

HLA immunogenetic heterogeneity in black American patients with Graves' disease.

Seventy-three American black patients with Graves' disease were typed for HLA-A, HLA-B, and HLA-DR antigens. There was a slight increase in HLA-DRw6 antigen frequency compared with 238 normal American black controls, but this was not significant after correction for the number of antigens tested. A significant increase in HLA-DR4 and HLA-DRw6 frequency was found in a subgroup of patients with exophthalmos (22.9% and 29.2% compared with 7.6% and 10.1% of normal black controls). There was a significant increase in HLA-DRw6 in a subgroup of patients who were thyroid antibody-positive (26.0%). The increment in HLA-DRw6 was higher in 32 patients who had both exophthalmos and who were antibody positive (37.5%). A significant increase in HLA-DR5 was found in a subgroup of patients who did not have exophthalmos and who were antibody-negative (83.3%). Our findings support previous evidence for immunogenetic heterogeneity in patients with toxic Graves' disease. In American blacks HLA-DRw6 is in some way associated with the disease in contrast to the well-recognized HLA-DR3 association in whites.

Black or African American↗

A study of 609 HLA haplotypes marking for the hemochromatosis gene: (1) mapping of the gene near the HLA-A locus and characters required to define a heterozygous population and (2) hypothesis concerning the underlying cause of hemochromatosis-HLA association.

We compared 609 haplotypes carrying the idiopathic hemochromatosis allele with 475 control haplotypes. Four haplotypes were more frequent in hemochromatosis: A3, B7 (actually A3, CW., B7, Bfs, DR2); A3, B14 (actually A3, CW., B14, BfF, DRW6); A11, B35; and A11, B5. The linkage disequilibrium for A3, B7 and A3, B14 (and probably also for A11, B5) was undeniably stronger in hemochromatosis than in controls. Two haplotypes--A3, B12 and A3, B15--were more frequent in hemochromatosis, without linkage disequilibrium. Four haplotypes in linkage disequilibrium in hemochromatosis--i.e., A2, B12; A1, B8; A9, B7; and A29, B12--were also found to have the same frequency and strength of linkage in controls. The dual observation (1) that haplotypes carrying A3 without either B7 or B14 were highly significantly more frequent in hemochromatosis than in controls and (2) that haplotypes carrying B7 or B14 but not A3 had the same frequency in hemochromatosis and controls led to the formal conclusion that only A3 is an independent marker for the hemochromatosis allele, B7 and B14 being involved only owing to the haplotypic mode of marking; the hemochromatosis allele can thus be mapped closer to locus A than to locus B. Our findings fit well with the hypothesis that the hemochromatosis mutation was a rare if not unique event that produced an ancestral HLA marking that was subsequently modified by recombinations and geographical scattering due to migrations.

Alleles↗

[B27-negative spondylarthritis. Results of 3 familial surveys, with monozygotic twins in one].

With the typing of the major histocompatibility complex (HLA, A, C, B, Bf, C4, DR, GLO), the authors study three (3) family investigations of patients suffering from primary ankylosing spondylarthritis, B27 negative, including one concerning a discordant pair of monozygotic female twins. The possible links between the patient's haplotypes and the phenotypic expression of their ankylosing spondylarthritis, B27 negative, is discussed: a complotype (C4 A4 B2) and 2 antigens (B18 and Bw62) from the group B35 CREG over-represented in ankylosing spondylarthritis (Family n degree 1): presence of antigen B40 of B7 CREG in the patient of Family n degree 2, contrasting with the presence of antigen B27 in 2 first-degree parents, apparently healthy; presence of antigen B7 from the B7 CREG and the possible role of an environmental factor in the discordant monozygotic female twins (Family n degree 3). The results are compared to the studies of families with ankylosing spondylarthritis, B27 negative, of monozygotic twins and discordant ankylosing spondylarthritis-antigen B27 reported in the literature. Pathogenetic implications are discussed (linked gene hypothesis, direct role and/or heterogeneity of B27).

Adult↗

Multiple myeloma in two brothers. An immunochemical and immunogenetic familial study.

When multiple myeloma was diagnosed within 6 months in two brothers a family study was carried out in 34 relatives to assess the genetic factors involved. The monoclonal immunoglobulin isotype identified was identical for the two brothers (IgG kappa) as well as their genotype (a = A2B12BfSDR4 GIo2/d:A9B27BfSDR2GIol). Blood protein electrophoresis and the major histocompatibility complex markers (HLA A, B, DR, Bf, glyoxalase phenotypes) were also determined in the other family members. The immunochemical study revealed no other case of monoclonal gammapathy, but 12 cases of low gamma-globulin and three cases of polyclonal hypergammapathy were found. The immunogenetic study showed that no other family member had the a/d genotype of the two brothers, whereas nine family members were semi-identical for haplotype a and five for haplotype d. It is unlikely that a double immunochemical and immunogenetic identity in two siblings with multiple myeloma would be due only to random encounter, rather this finding suggests that, besides environmental factors, genetic factors may be involved in the pathogenesis. Systematic immunochemical and immunogenetic studies in familial multiple myeloma are proposed as a method to further elucidate an eventual genetic background in multiple myeloma.

Agammaglobulinemia↗

Transmissibility of human immunodeficiency virus in haemophilic and non-haemophilic children living in a private school in France.

In a study of the transmissibility of human immunodeficiency virus (HIV) in haemophilic and non-haemophilic children living together in a boarding school in France, half of the haemophilic children had seroconverted by the end of a 3-year study period. By contrast none of the non-haemophilic children seroconverted. All children had had close casual contact, some of them for several years. Hepatitis B virus (HBV) markers detected in all polytransfused haemophiliacs were found in 4 of 20 control children in the school, whereas all healthy youngsters living with their families were HBV negative. This study adds support to the theory that transmissibility of HIV among casual contacts is low and that there is no reason to exclude HIV-antibody carriers from communities.

Acquired Immunodeficiency Syndrome↗

An influenza A virus-specific and HLA-DRw8-restricted T cell clone cross-reacting with a transcomplementation product of the HLA-DR2 and DR4 haplotypes.

The clone TA10 is a T3+ T4+ T8- proliferative and cytolytic human T cell clone. This clone has been shown to be specific for the hemagglutinin of influenza A Texas virus and restricted by an HLA class II molecule associated with the DRw8-Dw8.1 phenotype. Here we show that TA10 and all of its subclones can also react with eight HLA-DRw8 negative, Epstein-Barr virus (EBV)-transformed cell lines or phytohemagglutinin blasts in the absence of influenza antigens. All of these cell lines are HLA-DR2/DR4 with a classic DR2 long haplotype. The only nonreactive HLA-DR2/DR4 cell line observed bears a DR2 short haplotype. Only heterozygous HLA-DR2/DR4 but not parental DR2 or DR4 EBV-transformed cell lines can be recognized by TA10, indicating that the cross-reacting determinant is a transcomplementation product between HLA-DR2 and HLA-DR4 haplotypes. DR-specific, but not DQ- or DP-specific monoclonal antibodies, inhibit in the proliferation assay and in the chromium release test both the DRw8-Dw8.1-restricted and the anti-DR2/DR4 reactions. These results show that HLA-DR-restricted, anti-viral human T cell clone can evidence cross-reactivity for allospecific class II molecules of the major histocompatibility complex, and human CTL can recognize transcomplementation products of class II HLA genes. In addition, the results suggest that a beta-chain coded for by an HLA-DR gene and associated with an alpha-chain coded for by a still unidentified but possibly HLA-DQ gene constitute this functional transcomplementation product.

Antibodies, Monoclonal↗

DNA polymorphism related to the idiopathic hemochromatosis gene: evidence in a recombinant family.

The metabolic error involved in idiopathic hemochromatosis, as well as the underlying genetic defect remain unknown. It has, however, been recently shown that this genetic lesion occurs at a locus linked to the major histocompatibility complex, probably close to the HLA-A locus, and that the disease is recessively transmitted. Therefore, in a family where one subject has idiopathic hemochromatosis his HLA-identical siblings should also be affected. We present here the restriction polymorphism with two MHC class I probes and one DR beta probe in an exceptional family with three HLA-identical siblings: one (the proband) has a major form of idiopathic hemochromatosis, while the other two are free of any clinical or biochemical signs of the disease. The restriction patterns observed after DNA digestion by enzymes EcoRI, EcoRV, BglII, BamHI, PvuII, TaqI, HincII, and HindIII led to the conclusion that one of the proband's chromosome 6 had undergone two alterations: one, a deletion in the DR region, was revealed by missing fragments all correlated with DR5; the other was an unbalanced cross-over or a genetic conversion in the MHC class I region. This latter alteration was revealed by modifications in the patterns of high molecular weight HindIII bands which hybridize with probe pHLA2 and also by the absence of a HindIII fragment of 7.4 kb hybridized by another class I probe. This latter alteration most likely involved the hemochromatosis gene and could be the first step toward a molecular approach to this gene.

Adult↗

New class I in man: serological and molecular characterization.

New class I antigens in linkage disequilibrium with HLA-A antigen are demonstrated in PHA T and EBV preferential target cells using human alloantisera. These new antigens are defined as class I antigens by immunoprecipitation of a 41-12 k dimer. The molecule is shown to be distinct from the HLA-A, -B, -C molecule and in particular from the A3 molecule as in sequential immunoprecipitations, the depletion of the HLA-A, -B, -C molecule or A3 molecule (44-12 k) has no effect on the new molecule (41-12 k). Being present on the PHA T cells and lymphoblast lines, these antigens are considered as new epitopes involved in the the cell activation process.

B-Lymphocytes↗

T lymphocyte subsets at various stages of hyperthyroid Graves' disease: effect of carbimazole treatment and relationship with thyroid-stimulating antibody levels or HLA status.

Markers of autoimmunity in hyperthyroid Graves' disease were studied at various stages of the disease in connection with HLA status. The 148 patients studied were included in a long term prospective evaluation of antithyroid drug treatment. The proportions of total T lymphocytes and OKT4 and OKT8 positive cells in peripheral blood and circulating thyroid-stimulating antibodies were determined before treatment (M0; 46 patients), after 6 (M6; 50 patients), and 18 months (M18; 22 patients) of carbimazole treatment, at relapse (15 patients) and after 2 yr of euthyroidism after drug withdrawal (remission; 23 patients). Twenty-seven patients were sequentially studied between M0 and M6, and M6 and M18. As compared to matched normal subjects, the mean proportion of OKT8 positive cells was significantly decreased in every group of patients, even in those in remission, and the mean OKT4/OKT8 cell ratios were increased in all groups except the patients in remission. However, OKT4/OKT8 cell ratios in individual M0 patients were widely distributed, being normal in 50%. No correlation was found between the proportions of T cell subsets and thyroid-stimulating antibody values, and the two measures varied independently in patients studied sequentially. OKT8 lymphocyte subset was dependent on HLA status. In DR3-positive patients, the mean OKT4/OKT8 cell ratio was high at all stages of the study; in DR3-negative patients it decreased significantly at M18 and was normal in those patients who had a remission. However, in the DR3-positive and -negative groups of patients, the mean OKT4/OKT8 ratios at M0 and at relapse were similar. In conclusion, the proportions of circulating OKT8 positive lymphocytes reflect only poorly the activity of the immune abnormalities in Graves' disease, but do correlate with HLA-DR3 status.

Adolescent↗

[Idiopathic hemochromatosis. Immunogenetics and diagnosis. Prevention by HLA genotypes].

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.

Alleles↗