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M Gueguen

Publications and source records attributed to M Gueguen.

At least 37 records · Page 2Linked to original sources
PubMed1989

A new antigen recognized by anti-liver-kidney-microsome antibody (LKMA).

Sera from 23 children with autoimmune chronic active hepatitis and positive for anti-liver-kidney-microsome antibody (LKMA), as defined by immunofluorescence, were analysed by Western blot (WB) and two-dimensional gel electrophoresis using rat liver microsomes as antigen, and by WB and dot-blot analysis with rat liver microsomal subfractions. Western blot analysis showed three patterns of reactivity: 13 sera recognized a 50 kD polypeptide, six sera a 66 kD polypeptide and four sera both of them. Two-dimensional gel electrophoresis, WB, and dot-blot analysis showed the 66 kD antigen to have a pI of 5.4 and to be located in the smooth domain of the endoplasmic reticulum. Western blot analysis using monospecific antisera against human IgG subclasses showed the LKMA directed against the 66 kD antigen to be mainly of the IgG1 subclass. These results indicate that LKMA associated with a subgroup of autoimmune hepatitis of children react with at least two different microsomal antigens in rat liver: (1) the 50 kD polypeptide, recently shown to be a cytochrome P-450 of the IID subfamily, and (2) a new antigen of 66 kD, the location of which suggests it may also be part of the mono-oxygenase complex.

Autoantibodies↗
PubMed1988

Anti-liver kidney microsome antibody recognizes a cytochrome P450 from the IID subfamily.

Children with autoimmune hepatitis have high serum titers of antibodies directed against a 50-kD protein of rat liver endoplasmic reticulum. Affinity-purified anti-50-kD antibodies were used to screen a rat liver cDNA library in lambda GT-11 expression vector. 12 immunopositive clones were obtained. Crossreactivities between fusion proteins of these clones and the 50-kD protein was demonstrated, and four clones were analyzed by restriction mapping, one of them by nucleotide sequencing. Complete identity was found between the restriction maps of two clones (LKMC1 and LKMC2) and that of the 5' end of the rat cytochrome P450 db2. Sequence of a 608-bp fragment of LKMC1 showed complete homology with the rat P450 db2 form. The restriction map of the other two clones (LKMC3 and LKMC4) was identical to that of rat P450 db1. These results suggest that the antigen recognized by LKMA is a P450 of the IID subfamily.

Animals↗
PubMed1987

Porphyria cutanea tarda and HLA-linked hemochromatosis. Evidence against a systematic association.

This study was designed to test the hypothesis that a hemochromatosis allele is implicated in the expression of porphyria cutanea tarda. HLA phenotypes were determined in 69 porphyria cutanea tarda patients, 42 of which had the sporadic type (normal erythrocyte uroporphyrinogen decarboxylase activity) and 27 unrelated patients who had the familial type (diminished erythrocyte uroporphyrinogen decarboxylase activity). The incidence of HLA antigen A3, a marker of the hemochromatosis allele, was identical in the sporadic patients (23.8%), in the familial patients (22.2%), and in the controls (24.5%). Furthermore, no clinical difference could be found between A3 and non-A3 patients. These results demonstrate no systematic association between hemochromatosis and porphyria cutanea tarda in the population studied. Another HLA-linked gene, however, could be implicated in the expression of the disease as HLA antigen DR7 presented an incidence statistically different (p less than 0.05) between sporadic (16.6%) and familial patients (43%).

Adult↗
PubMed1987

Immunological parameters in Graves' disease: are they useful for indication and monitoring of antithyroid drug treatment?

This paper reviews the available published data on studies of a correlation between the presence or intensity of measurable immunological abnormalities or markers in Graves' disease and the outcome after a course of antithyroid drug. The following parameters are discussed: circulating anti-thyroid-stimulating hormone receptor antibodies; antitubulin antibodies; human lymphocyte antigens, and repartition of T-lymphocyte subsets. At the present time no single parameter has any real practical value for individual patients either to indicate or monitor antithyroid drug therapy. The more useful information remains the anti-thyroid-stimulating hormone receptor level at the end of treatment which, if elevated, is predictive of relapse. Several areas of research, however, appear promising.

Antithyroid Agents↗
PubMed1987

[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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1985

Factor B (Bf) and glyoxalase genes in insulin-dependent diabetes mellitus.

The frequency distribution of alleles controlled by the factor B (Bf) and glyoxalase genes that are found close to the HLA system on chromosome 6 was studied in 170 insulin-dependent diabetic patients. The data were compared with those for HLA-A, -B and -DR antigens and were related to age of onset of diabetes. All the diabetics were ketosis prone and on permanent insulin therapy. A significant excess of BfF1 was seen in the diabetic patients (p less than 10(-4]. Glyoxalase frequency distribution showed no significant deviation from controls, whereas HLA-DR3 (p less than 10(-4] HLA-DR4 (p less than 10(-4] were increased. Breakdown of data by age of diagnosis of disease showed no increase in the frequency of BfF1 and GLO1-2 but an increase of HLA DR3 and DR4 in patients with early onset diabetes. The findings of the study are consistent with data reported by others investigators and support the notion that one or more genes mapping close to the HLA A. B and DR and to the Bf loci confer susceptibility to insulin dependent diabetes.

Alleles↗
PubMed1983

[Relapse in Basedow's disease after treatment with synthetic antithyroid drugs. Prognostic value of analysis of the HLA system].

One hundred and eleven unselected patients with hyperthyroidism due to Graves' disease received decreasing doses of carbimazole for 18 months. Clinical examination and hormonal assays (serum T3, T4, free T4 index) were done at 4, 9 and 18 months of treatment. Patients were typed for 35 HLA antigens and were followed up for 2 years after withdrawal of treatment; 39 patients were excluded for various reasons and 72 were retained for study. Of the 72 patients, 37 relapsed and 35 remained in remission: 40 patients were DR3+ (20 relapsed) and 32 were DR3- (17 relapsed). HLA frequency was not significantly different in patients who relapsed and in those who remained in remission. Thus, under the conditions of this study, HLA frequency could not be used to predict relapse of hyperthyroidism due to Graves' disease. This study brings out an other interesting point: relapse frequency of about 50% focuses our attention on the limits of medical treatment.

Carbimazole↗
PubMed1983

A prospective study of the relationship between relapse of hyperthyroid Graves' disease after antithyroid drugs and HLA haplotype.

One hundred and eleven unselected patients with hyperthyroidism due to Graves' disease received decreasing doses of carbimazole for 18 months. Clinical examination and hormonal assays (serum T3, T4, free T4 index) were done at 4, 9, and 18 months of treatment. Patients were typed for 35 HLA antigens and were followed for 2 yr after withdrawal of treatment; 39 patients were excluded for various reasons and 72 were retained for study. Of the 72 patients, 37 relapsed and 35 remained in remission; 40 patients were DR3+ (20 relapsed) and 32 were DR3- (17 relapsed). HLA frequency was not significantly different in patients who relapsed and those who remained in remission. Thus, under the conditions of this study, HLA frequency could not be used to predict relapse of hyperthyroidism due to Graves' disease.

Carbimazole↗
PubMed1983

Properdin factor B (Bf) and glyoxalase in Graves' disease.

Patients with Graves' disease were phenotyped for properdin factor B (Bf) and glyoxalase, which are coded for by genes mapping close to the HLA region on the sixth chromosome. Frequency data were analysed in relation to HLA-A, -B and -DR typing data. Diagnosis of Graves' disease was based on the usual criteria including elevated T3 and T4 levels and free T4 index and a homogeneous thyroid scan. Ninety-four patients with Graves' disease were phenotyped for properdin factor B (Bf) and 37 for red cells glyoxalase (GLO). HLA-A, -B and -DR antigens were typed in 94 patients using a lymphocyte microcytotoxicity assay. The frequency distribution of Bf and GLO alleles showed no significant differences from control subjects. This finding contrasts with the reports of an increased frequency of BfF1 in insulin-dependent diabetes mellitus. The difference in the two diseases which are both associated with an increased frequency of the antigen combination D8-DR3, is accounted for by linkage disequilibrium between B18 and BfF1.

Chromosome Mapping↗
PubMed1983

[The HLA-DR determinants in chronic inflammatory rheumatism].

The authors present a study of the incidence of HLA-DR antigens in 113 controls and in a Breton population suffering from chronic inflammatory rheumatism. They found 80 cases of rheumatoid arthritis and found a significant increase incidence of the DR4 antigen in rheumatoid arthritis (54% compared with 19.5%; pc less than 10(-4); RR = 4.8) and a decreased incidence of the DR2 antigen (12.5% compared with 35%; pc less than 10(-2); RR = 0.27). The increased incidence of DR4 does not seem to be related to the presence of rheumatoid factor. Out of the 95 cases of chronic inflammatory rheumatism treated, 33 cases of drug intolerance (cutaneous and/or renal to gold salts or D-penicillamine) were reported. The authors found a decreased incidence of the DR2 antigen in the patients who presented a drug intolerance, which was partially significant in the group of patients with rheumatoid arthritis (p less than 0.04; pc less than 0.3). This is an important argument in favour of the supposed protective role of this antigen.

Adult↗