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J Hors

Publications and source records attributed to J Hors.

At least 91 records · Page 5Linked to original sources
PubMed1988

A new method to test genetic models in HLA associated diseases: the MASC method.

We propose a new method to analyse data on HLA associated diseases. The method uses the simultaneous information on the marker associations and segregation with the disease. It may also take into account the differential risk of being affected for specific relatives of a patient as well as the differential HLA haplotype sharing according to the marker genotype of the patient. It is based on the principle of minimization of a sum of independent chi-squares. It allows us to test the goodness-of-fit of various models in an easy and economical way. The method is applied to a sample of 269 French IDDM patients and their relatives leading to the rejection of models with one locus closely linked to HLA with two and three alleles.

Alleles↗
PubMed1988

Inhibition of insulin release in vitro mediated by mononuclear cells from diabetic patients treated with cyclosporin A or placebo.

Anti-beta-cell-specific cell-mediated immunity was studied over a 12-mo period in 65 recently diagnosed diabetic patients randomly receiving either cyclosporin or placebo. Anti-beta-cell cellular immunity was assessed by an in vitro test based on the inhibition of insulin release from cultured rat islet cells by patients' mononuclear cells. This beta-cell-suppressive effect disappeared in cyclosporin A-treated patients within 1 mo and did not reappear during 12 mo of follow-up. Conversely, the suppressive effect persisted unchanged in placebo-treated patients during 12 mo of follow-up. These changes were predictive neither of cyclosporin A-induced remission nor of relapses. Results of the insulin-release inhibition test were not correlated to islet cell autoantibodies or HLA phenotype.

Adolescent↗
PubMed1988

[Endocrine polyadenomatosis of 2a type (MEN 2a). Clinical and genetic study of a family].

In a large kindred with multiple endocrine neoplasia type 2a (MEN 2a) (137 members, 5 generations), bilateral thyroid medullary carcinoma was found in all affected members. Pheochromocytoma was present in 59% of the cases, and was responsible at least for 4 out the 5 deaths related to MEN 2a. Hyperparathyroidism was less frequent (41%). Family screening leads to a reduction in age for diagnosis and to an improvement in the prevalence of complete healing after surgery. Linkage between HLA loci and a dominant gene for MEN 2a was investigated in this kindred. Lod scores for recombination fraction were all negative (-0.47 for a recombination fraction of 0.05). These results comfort the lack of linkage between MEN 2a and the HLA complex.

Adolescent↗
PubMed1987

A Gm haplotype study in relation with HLA-DR in 155 insulin-dependent diabetic patients and their affected and non affected siblings.

In order to assess interaction between HLA and Gm for susceptibility to IDDM, the families of 155 IDDM probands were typed for HLA class I, II, III antigens and 16 Gm allotypes (including G2m23). Haplotypes were obtained for both systems. Individuals bearing the equivocal haplotype Gm (formula; see text) were excluded. The frequencies of the 6 Gm haplotypes detected were comparable in IDDM patients, sibling controls and unrelated controls. The number of Gm haplotypes was compatible with random segregation whether or not the HLA genotype was taken into account. However, analysis of the HLA-DR allelic combinations showed an increase of the uncommon haplotype Gm (formula; see text) in IDDM patients bearing DR3 in the absence of DR4 (Gm (formula; see text) phenotype frequency 43% vs 24% in other allelic combinations, p less than 0.04). When 21 diabetic and 154 non diabetic siblings of the probands were compared, the combined presence of DR3/ non 4 and Gm (formula; see text) was observed in 7 (33%) affected and 11 (7%) unaffected siblings (p less than 0.001), conferring a relative risk of 6.4 to siblings who bear both markers. All DR3/non 4 positive affected siblings (7/7) also carried Gm (formula; see text) compared with 27% (11/41) of unaffected siblings (p less than 0.001). This result suggests, that in spite of the absence of segregation distortion, interaction between Gm and HLA gene products may play a role in the familial penetrance of IDDM.

Adolescent↗
PubMed1987

Susceptibility to human cutaneous leishmaniasis and HLA, Gm, Km markers.

A relationship between markers related to the immune response (HLA system, Gm and Km immunoglobulin allotypes) and susceptibility to cutaneous leishmaniasis was investigated in a population of Hmong refugees who had recently settled in French Guiana. Two approaches were used: 1) case/control comparisons of the marker phenotype distribution to detect possible associations; 2) multiple-case family studies to search for marker-linked genes. When the distribution of HLA-A, B, C, antigens and Gm, Km allotypes was compared between patients and controls, only a significant decrease of HLA-Cw7 antigen among leishmaniasis patients was detected (p = 0.01). No interaction between any two of these markers and the disease was found. On the other hand, neither an HLA, Gm or Km susceptibility gene could be demonstrated in the informative sets of affected siblings. These results are discussed with respect to those reported in other infectious diseases.

Disease Susceptibility↗
PubMed1987

Effect of cyclosporin A treatment on the production of antibody in insulin-dependent (type I) diabetic patients.

Anti-islet cell and anti-insulin antibody production was studies over a 12-mo period in 82 recently diagnosed diabetics randomly receiving either cyclosporin or placebo. Cyclosporin had only minimal effects on the production of anti-islet cell antibodies whether directed to islet cytoplasmic (immunofluorescence) or membrane (cytotoxicity assay) antigens even in patients undergoing remission. These data suggest that these antibodies do not play a major role in the pathogenesis of the disease particularly since their (irregular) presence is not predictive of the clinical response to cyclosporin. Conversely, cyclosporin completely suppressed the synthesis of antibodies elicited by exogenous insulin irrespective of the insulin doses received, and decreased the autoantibody production against thyroid antigens, indicating that cyclosporin has variable effects on antibody production against various antigens.

Antibody Formation↗
PubMed1987

[Influence of the anti-HLA immunization profile before grafting on the outcome of renal transplant].

A retrospective study of HLA immunization profile before a first graft of unrelated kidney in 212 immunized recipients (with an initial peak greater than or equal to 25%) shows that one can define at least 3 groups of responder with a different graft outcome. Recipients with either weak or strong variance of HLA antibody (VP) before graft (group I: VP less than 230 and group III: VP greater than 830) have a significantly lower graft survival: 54% (p = 0.006) and 45% (p = 0.002) respectively at 4 years, than recipients of group II (230 less than VP less than 830) for whom the prognosis is of 77% after the same time period. If similar results are observed on independent series, VP would be of a great interest for the definition of a new classification of responders, and on a practical level for the choice of renal transplant.

Antibodies↗
PubMed1987

Particular interest of HLA typing for genetic counselling in families with congenital adrenal hyperplasia (21-OH deficiency).

The close genetic linkage between 21 hydroxylase deficiency and HLA loci considerably enlarges the possibilities of genetic counselling. Two 21-OH deficient complex families are reported, illustrating several aspects of this genetic counselling: detection of carriers, determination of the actual risk to related couples, suspicion of 21-OH deficiency by an HLA specificity association, and prenatal diagnosis.

Adrenal Hyperplasia, Congenital↗
PubMed1987

[HLA and molar pregnancies (triploidies, hydatidiform moles and choriocarcinoma). Etiological and epidemiological study].

Etiological and epidemiological studies of triploid and hydatidiform molar conceptuses were done using HLA polymorphism. The segregation of HLA markers allowed to know the etiology of 25 triploidies and 19 hydatidiform moles. Five other moles and a post molar choriocarcinoma were also studied by molecular hybridization. This confirms that triploidies in about 3/4 of the cases involved two sets of paternal chromosomes mainly by di-sperm. Hydatidiform moles from Algeria, France and Senegal were all of androgenic origin excepted for one case. DNA analysis of the choriocarcinoma demonstrated the presence of a paternal marker suggesting for this case a direct cellular lineage from the mole. Positive associations with HLA A 28 and B 7 were found which could be related to gametogenesis-fecundation dysfunction. A slight excess of antigens shared by parents of triploidies was shown. This was not observed for parents of hydatidiform moles but when they shared HLA antigens a preferential inheritance in the mole of the shared specificities was observed. This relative compatibility of the molar conceptus with the mother may be an element of the process that prevent its early rejection.

Choriocarcinoma↗
PubMed1986

[4 varieties of islet cell antibodies in 74 insulin-dependent diabetics and their families as a function of the HLA genotype].

The sera of 74 diabetic patients and of their first degree relatives were studied for 4 different types of islet cell antibodies (ICA, CFICA, ICSA, ICACT) and the results were compared according to the HLA genotype. Seventy two percent of the patients' sera were positive for at least one type of auto-antibody. Two types of auto-antibodies were observed: anticytoplasmic antibodies (ICA and CFICA), and surface antibodies (ICSA and ICACT). The different types of antibodies were not associated with any HLA-DR. These antibodies were also present in 15% of the healthy relatives. The fact that they were detected in the sera of siblings sharing no haplotype with the proband, some of them bearing neither DR3 nor DR4 antigens, suggests that non HLA linked genes and/or environmental factors partly control their secretion.

Autoantibodies↗
PubMed1986

HLA antigens in acute measles encephalitis.

The frequency of HLA-A, B, DR antigens was studied in 24 patients with acute measles encephalomyelitis compared to 1926 control subjects. The results demonstrated no association between the susceptibility to the disease and HLA markers. However, DR4 was observed in 6 patients out of 10 who developed intrathecal secretion of specific antimeasles immunoglobulins, while absent in 4 patients, who did not (p less than 0.04). Further studies on a larger series are needed.

Child↗
PubMed1986

Interactive effect of HLA and Gm tested in a study of 135 juvenile insulin-dependent diabetic families.

Interaction between HLA and Gm for susceptibility to insulin-dependent diabetes (IDD) has been studied in 135 IDD families comparing HLA and Gm phenotype distributions in patients and sibling controls. The association analysis comparing the 135 index cases to 124 sibling controls did not show any significant interaction, but only a tendency for Gm 4,5 phenotypes to be more frequent in IDD patients, particularly in those who carried DR3/X. The sib pair analysis of 16 pairs of affected sibs did not show any distortion of segregation of Gm. On the other hand, among 98 sib pairs of one affected and one nonaffected sib, there was a significant distortion in favour of sib pairs with non-identical Gm phenotypes. However, no interaction between HLA and Gm was found. These results provide suggestive evidence that Gm or a locus very close to Gm could be involved in susceptibility to IDD.

Adolescent↗
PubMed1986

HL-A and disease.

Of more than 500 diseases or syndromes studied for HL-A markers, more than 40 are known to be associated with an allele of class I, II, or III. Seven are linked to the HL-A region: six are recessive (idiopathic hemochromatosis, C2, C4A, and C4B deficiencies, congenital and late-onset deficiencies) and one is dominant (spinocerebellar ataxia). In addition, insulin-dependent diabetes mellitus is also linked to HL-A with more than one single locus. HL-A typing is of practical interest for diagnosis of ankylosing spondylitis by B27 antigen determination and for prevention of idiopathic hemochromatosis by genotyping of siblings of the index case. Prenatal diagnosis of 21-OH deficiency by genotyping fetal cells permits genetic counseling. Indeed, the discovery of the relationship between HL-A and disease can be considered a new approach to medical genetics. Extensive use of HL-A technology will probably allow better prediction of risk and may elucidate the mechanisms of certain diseases. For the first time the study of one single immunogenetic system may have a significant effect on public health through the possibility of wide-scale prevention.

Alleles↗
PubMed1986

[Distortion of the maternal segregation of the silent alleles of complement factor 4 in normal and diabetic families].

54 normal Caucasian families and 169 families in whom at least one child had type I diabetes (IDDM) were genotyped for HLA-A, B, C, DR and for the complement factors Bf and C4. The paternal and maternal transmission of the different alleles and of haplotypes and complotypes in linkage desequilibrium have been analysed. No distortion of the paternal transmission has been observed in the offspring of the two series of families. On the contrary, a distortion of the maternal segregation of the silent alleles at the complement factor C4A and B locus was found: mothers transmitted C4AQ0 more often than expected to their male offspring (p less than 0.04 in normal families, p less than 0.001 in IDDM families) while they transmitted C4BQ0 in excess to their female offspring (p less than 0.01 and p less than 0.03 in normal and IDDM families, respectively).

Alleles↗