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Biomedical subjects

I Deschamps

Publications and source records attributed to I Deschamps.

At least 73 records · Page 4Linked to original sources
PubMed1985

A systematic study of HLA class II-beta DNA restriction fragments in insulin-dependent diabetes mellitus.

DNA restriction fragments of the genes encoding HLA class II-beta antigens were compared in 34 patients with insulin-dependent diabetes mellitus and 34 HLA-DR-matched healthy individuals. Ninety-three fragments, determined by six restriction enzymes (EcoRI, EcoRV, HindIII, BamHI, Pvu II, and Taq I), were analyzed: (i) A DR Taq I 12.7-kilobase-pair fragment might be a marker for the extended haplotype HLA-B8, DR3. (ii) In controls, DR4 haplotypes are associated with two distinct clusters of DQ restriction fragments (DQR4 and DQR5). Almost all (94%) DR4 patients belong to the DQR4 and not to the DQR5 cluster. This suggests that, among HLA-DR4 haplotypes, only DQR4 haplotypes are involved in susceptibility to insulin-dependent diabetes mellitus. (iii) A DR Taq I 14.5-kilobase-pair fragment was found to be strongly associated with DQR4, mainly in DR3/DR4 heterozygous patients (P = 5 X 10(-4). However, these results must be interpreted with caution, taking into account the high number of statistical tests performed.

DNA Restriction Enzymes↗
PubMed1985

[Interaction between HLA and Gm for susceptibility to insulin-dependent diabetes].

It is now well established that HLA system is involved in the susceptibility to Type 1 diabetes mellitus. In this study we look for a possible effect of the Gm system. A first study (cases-controls) suggests that among individuals who had HLA-DR3 but not HLA-DR4 or HLA-DR4 without HLA-DR3, there is a possible effect of the phenotype Gm3,23,5 or Gm3,-5 in the susceptibility to IDDM. Moreover, we have tested by the sibpair method whether HLA and Gm are transmitted independently from IDDM: an unaffected sib, sharing the same HLA haplotypes than an affected individual, seems to be more often phenotypically different at the Gm loci.

Diabetes Mellitus, Type 1↗
PubMed1984

Detection of islet cell antibodies by a microcytotoxicity method.

A microcytotoxicity test for antibodies against islet cells (ICA) is described. Sera from patients with insulin-dependent diabetes, their healthy first degree relatives, and normal controls, genotyped for HLA-A, -B and -DR, were tested by 4 different methods. Cytoplasmic ICA and complement fixing ICA were detected by indirect immunofluorescence with human pancreas sections, and cytotoxic complement dependent ICA and surface ICA were tested against murine beta cell suspensions. Strong correlation was found between cytotoxic and surface antibodies (P less than 10(-7). The technique described is appropriate for use in the screening of large numbers of sera.

Animals↗
PubMed1984

Segregation of HLA-DR2 among affected and non-affected offspring of 66 families with type 1 (insulin-dependent) diabetes.

Segregation of HLA-DR2 among affected and unaffected offspring was studied in 66 HLA-genotypes families with Type 1 diabetes in whom at least one parent carried DR2. The frequency of DR2-positive parents (21%) was not different from that of control families (29%). Among the diabetic probands, the gene frequency of DR2 was significantly decreased compared with control subjects (0.05 versus 0.17, p less than 0.001) as were DR5 (0.07 versus 0.17, p less than 0.01) and DR7 (0.06 versus 0.13, p less than 0.003). Twenty probands carried DR2, in 11 or whom (55%) it was found in combination with either DR3 or DR4. The nine cases who carried another DR allele included one who was DR2 homozygous. Transmission of DR2 was reduced in affected offspring, and random in unaffected siblings, compared with the expected ratio. However, when the DR2 transmission was analysed separately for parents bearing DR2 with DR3, DR4 or another DR allele, it appeared that DR2 transmission to affected offspring was random when the parents carried neither DR3 or DR4, the transmission deficit being due to over-transmission of DR3 and DR4. The haplotype analysis showed that the haplotype A3, Cw7, B7, GfS, DR2, found in 19% of "non-diabetic" DR2 haplotypes was practically absent among "diabetic" DR2-haplotypes (4%). In conclusion, population and segregation analysis could not demonstrate a specific protective effect of DR2.

Diabetes Mellitus, Type 1↗
PubMed1984

Genetic polymorphism of the fourth component of complement and type 1 (insulin-dependent) diabetes.

The complement proteins, Bf, C2, C4A and C4B, are closely linked to HLA. In 74 propositi and their families, and 97 controls genotyped for HLA-A, -B, -C, DR, -Bf, a high incidence of the C4BQ0 variant was detected in the patient group (33% versus 12%, p less than 0.00001); C4BQ0 was more frequent in propositi than in non-affected siblings (40 out of 74 versus 36 out of 92, p less than 0.05). When comparing the distribution of the phenotype C4BQ0 in Type 1 diabetic patients and normal control subjects, the difference was significant in patients bearing DR3 or DR4 (56% and 25%, respectively, p less than 0.003). The main linkage disequilibria were observed among the 74 propositi: B18, BfF1, C4, A3, BQ0, DR3; B12, BfS, C4, A3, BQ0, DR4. The existence of a silent allele at the C4 B locus is known to be associated with a defective immune response.

Complement C4↗
PubMed1984

Islet-cell antibodies (ICA-CFICA) and HLA genotypes in 107 IDD patients and their first-degree relatives.

The prevalence of ICA and CFICA in relation to HLA-DR genotypes was analyzed in 107 insulin-dependent diabetic (IDD) patients with a duration of IDD ranging from onset to 30 years, and 247 nondiabetic first-degree relatives. In 46 patients tested at onset of IDD, the prevalence of ICA and of CFICA was 61 and 50%, respectively; with the longer duration of IDD, the prevalence of CFICA decreased more rapidly than that of ICA. No significant association was observed between ICA and any HLA allele in patients tested from onset till 2 years after onset. However, a higher prevalence of ICA was found in DR3 positive patients with a duration of IDD of more than 2 years (p less than 0.02). Among the healthy relatives, the prevalence of ICA was 7% in parents and 13% in siblings; one out of 101 siblings had CFICA. No association was found between ICA and any HLA marker. The presence of ICA in sibs was independent of the number of haplotypes they shared with the IDD proband: among the 13 ICA-positive healthy sibs, one shared 2 haplotypes, nine shared 1 haplotype and three shared no haplotype with the proband, which is not different from the random distribution.

Adolescent↗
PubMed1984

Class II HLA-DC beta-chain DNA restriction fragments differentiate among HLA-DR2 individuals in insulin-dependent diabetes and multiple sclerosis.

HLA-DR2 allele is negatively associated with insulin-dependent diabetes and positively associated with multiple sclerosis (MS). A 2.2-kilobase-pair EcoRI DNA restriction fragment detected with a beta-chain HLA-DC cDNA probe was found to be strongly correlated with HLA-DR2 in the normal population, but was absent in HLA-DR2 insulin-dependent diabetic patients. This fragment was found in HLA-DR2 multiple sclerosis patients with the same frequency as in controls. A beta-chain HLA-DC 12-kilobase-pair BamHI fragment might differentiate multiple sclerosis patients from healthy individuals.

DNA Restriction Enzymes↗
PubMed1984

Evaluation of recurrence risk in siblings of diabetic children: importance of age and birth order in relation to HLA genotypes.

In order to identify factors other than the HLA-linked susceptibility involved in the risk to the siblings of diabetic children, we compared the age at onset, birth order and HLA genotypes in 23 IDD multiplex (Mx) families and 140 simplex (Sx) families. The results showed a relationship between age and recurrence risk in sibs. Probands (= 1st affected sibs) of Mx families were significantly younger at onset (5.8 +/- 0.8 yr) than probands of Sx families (9.0 +/- 0.4 yr, p less than 0.01). The 2nd affected sibs of Mx families, although affected at an older age (12.4 +/- 1.6 yr), had been significantly younger at the time of the proband's onset, than the siblings who have remained unaffected (6.2 +/- 1.2 vs 11.5 +/- 0.5 yr, p less than 0.01). Probands of Mx families were more often the first born and probands of Sx families, more often came later in the birth order (p less than 0.02). Prevalence of IDD was higher among siblings born after than among those born before the proband (12% vs 4%, p less than 0.002). The HLA haplotype distribution in unaffected siblings deviated from the random assortment in relation to birth order, showing an excess of HLA-identical sibs born before the proband and, inversely, an excess of non-identical sibs born after the proband. The results suggest that age-dependent factors are likely to increase the penetrance of HLA-linked IDD susceptibility. These factors could be related to the environmental insult. However, a genetically determined form of type I diabetes characterized by higher familial penetrance and earlier onset cannot be ruled out.

Age Factors↗
PubMed1983

[Genetic and environmental factors in insulin-dependent diabetes].

Insulin-dependent diabetes results from the interaction of genetic, immunological and environmental factors. In view of the association between insulin-dependent diabetes and HLA system, it has been postulated that the diabetogenic gene(s) is (or are) located in the region of the DR locus in that system. The hypothesis of viral factors is supported by epidemiological arguments and experimental models but has only been exceptionally confirmed in man. The fact that anti-islet antibodies are frequently detected at the onset of insulin-dependent diabetes or even before the first symptoms develop suggests that an auto-immune mechanism might be involved in the destruction of beta-cells. Although the mode of inheritance of genes supposed to predispose to insulin-dependent diabetes as well as the mechanisms behind the pancreatic lesion are still poorly understood, determining "markers" of the disease should eventually make it possible to detect subjects at risk of diabetes and to prevent its development.

Antibody Formation↗
PubMed1983

HLA-DR2 in two sibships with insulin-dependent diabetes mellitus.

We report two families selected from 124 genotyped Caucasian insulin-dependent diabetes mellitus (IDDM) families because of unusual features. In both families, all offspring are affected and four out of six bear the allele HLA-DR2 which is an uncommon phenotype among diabetic patients. Onset before the age of 1 year in all the patients of one family, association with optic atrophy in the other, and the existence of pairs of affected sibs of different HLA types in both, are infrequent findings and support the evidence of heterogeneity in IDDM.

Age Factors↗
PubMed1983

Age--related heterogeneity of insulin-dependent diabetes mellitus.

One hundred and thirty-three insulin-dependent diabetic (IDD) patients were genotyped for HLA-A, B, C, DR and 123 of them for Bf. The study shows a relationship between these genes and the age of onset of diabetes and emphasizes the possible heterogeneity of the disease. When patients under the age of 0 years at the onset of the disease were compared with those aged 11 to 29 years, a significant excess of HLA-B18 (41% versus 15%, p less than 0.001) and BfF1 (40% versus 21%, P less than 0.05) was observed. The haplotype B18, BfF1 was also more frequent in the first group of patients (haplotype frequency 18% versus 6%, p less than 0.02). The frequency of the whole haplotype Cw5, B18, BfF1, DR3 and of its segment BfF1, DR3, and the strength of the gametic associations between these alleles were much higher in IDD patients than in non-diabetic controls, irrespective of the age of onset of their diabetes. The association between early age of onset of IDD and the B18, BfF1 haplotype independently of DR3 (no association between age and DR3) suggests that a factor influencing the onset of the disease in young children could be under the control of (1) gene (s) in linkage disequilibrium with B18 and/or BfF1.

Adolescent↗
PubMed1982

HLA haplotype study of 53 juvenile insulin-dependent diabetic (I.D.D.) families.

R4 heterozygotes was observed. By contrast, the observed frequency of patients homozygous for DR3 or DR4 was not increased, but even slightly decreased. The data support a model of inheritance comprising at least two closely linked specifically "diabetic" loci (most of the time marked by B18, BfF1, DR3 and B15, BfS, DR4) and a non-specifically "diabetic" haplotype favouring auto-immunisation (most of the time marked by B8, BfS, DR3). This model is discussed in the light of the presented data and of those of the literature.

Adolescent↗
PubMed1982

Circadian metabolic rhythms in obese children.

Obese children display constant hyperinsulinism and, frequently, hyperphagia. In animals, lesions of the hypothalamic system affect simultaneously the circadian rhythm of insulin secretion and of food intake. In this study, circadian metabolic rhythm was examined in obese and non-obese children, by two different protocols. (1) Oral glucose tolerance tests (OGTT) were carried out at 9 a.m. and 3 p.m. on 2 consecutive days. (2) Circadian variations of plasma glucose and insulin were determined. After OGTT, in the control children there was a significant drop in the insulin/glucose ratio in the afternoon, whereas in the obese group this ratio remained high, with no significant change during the day. Differences were also observed in free fatty acid, growth hormone, and cortisol responses. The control children showed a circadian rhythm for blood glucose levels which was not present in obesity. These preliminary data suggest impairment of metabolic rhythms in obese children; they should stimulate further studies on the hypothalamic system in obesity.

Adolescent↗