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J Bertrams

Publications and source records attributed to J Bertrams.

At least 37 records · Page 2Linked to original sources
PubMed1990

Antibodies to proinsulin and insulin as predictive markers of type 1 diabetes.

The aim of the present study was to test whether proinsulin autoantibodies (IgG-PAA), insulin autoantibodies (IgG-IAA), and islet cell antibodies (ICA) may be used to identify subjects at risk for Type 1 diabetes. Pre-diabetic sera from 18 individuals who later developed diabetes were tested. Results were compared with 18 age-, sex-, and HLA-DR-matched non-diabetic control subjects from families with Type 1 diabetes. At a mean of 2.4 yr before the onset of diabetes, ICA were found in 13 patients (vs 0 control subjects, p less than 0.001), ELISA-determined IgG-IAA in 8 patients (vs 1 control subject, p less than 0.05) and ELISA-determined IgG-PAA in 4 patients (vs 2 control subjects, NS). ELISA-determined IgG-PAA do not appear to be useful predictors of the future development of Type 1 diabetes.

Adult↗
PubMed1990

Gene and haplotype frequencies of HLA antigens in 269 patients with Crohn's disease.

Evidence of strong genetic markers in Crohn's disease (CD) is still absent. Many investigations have focused on HLA antigens, with conflicting results. To obtain more detailed information on the relation of HLA to the disease, we used the HLA data from 269 CD patients to compute the maximum-likelihood estimates of HLA gene and haplotype frequencies. These results provide further evidence that HLA B44 and Cw5 do indeed play a role in the development of CD. Furthermore, it is conceivable from our results that HLA Cw7 may protect against being affected with this disease.

Chi-Square Distribution↗
PubMed1990

Crohn's disease in four members of a family, two of whom are dizygotic twins.

Familial occurrence of Crohn's disease (CD) is well known, but the disease is rarely reported to occur in dizygotic twins. We present an additional case of dizygotic twins, both of whom developed CD, from a family in which two other members are affected. The 16-year-old son contracted the disease 2 years before his 50-year-old father, and 13 years before his twin sister. Another sister was affected 6 years after the onset of the disease in the propositus. HLA haplotyping of the three children matched the Mendelian ratio. The multiple occurrence of CD in blood relatives, especially in siblings, emphasizes the importance of genetic factors in the development of this disease. This family history, however, could point to psychic influences promoting the occurrence of CD on the basis of a polygenic disease susceptibility.

Adolescent↗
PubMed1989

Prevalence of cytoplasmatic islet cell antibodies and insulin autoantibodies is increased in subjects with genetically defined high risk for insulin-dependent diabetes mellitus.

The presence of cytoplasmatic islet cell antibodies (ICA) and IgG insulin autoantibodies (IgG-IAA) has been observed in the prediabetic state of type 1 (insulin-dependent) diabetes (IDDM). We therefore analyzed the prevalence of these markers in sera from 1117 healthy HLA-typed first-degree relatives (1 degree Rel) of IDDM patients. ICA was determined by indirect immunofluorescence on cryostat sections of human pancreas. For IgG-IAA measurement a competitive solid-phase ELISA was used. ICA were present in 3.5% of 1 degree Rel vs 0.4% of controls (P less than 0.025). The highest frequencies of ICA were found in individuals of IDDM multiplex families (7.7%) and HLA-DR1,3 (5.4%), -DR1,4 (5.8%), and -DR3,4 (6.7%) positive subjects. We therefore conclude that the prevalence of ICA is increased in 1 degree Rel with high genetic risk for diabetes. IgG-IAA occurred in 9.9% of 1 degree Rel vs 1.4% of controls (P less than 0.01). Like ICA, IgG-IAA were significantly increased in a group of subjects being positive for either HLA-DR1,3 -DR1,4, or -DR3,4 (16.5%, P less than 0.01). In multiplex families, however, prevalence of IgG-IAA was not increased. In contrast to ICA there was an additional influence of age and sex: IgG-IAA were found more often in siblings (mean age, 16.6 years; prevalence, 15.0%) than in parents (mean age, 44.1 years; prevalence, 8.3%) of IDDM patients (P less than 0.01). In brothers the prevalence of IgG-IAA is higher than in other 1 degree Rel. Only a weak association between ICA and IgG-IAA was observed in subjects (n = 810) tested for both antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Genetic analysis of IDDM: the GAW5 multiplex family dataset.

In a collaborative effort by 12 centers from Europe and North America, data were assembled from 94 multiplex families with insulin-dependent diabetes mellitus (IDDM) for analysis of genetic and other factors of possible etiological importance. The dataset contains information on the following genetic markers: HLA-DR beta and -DQ beta restriction fragment length polymorphisms (RFLPs), three RFLPs detected with two probes that map 5' to the insulin gene, the serologically defined HLA loci, and the immunoglobulin allotypes. Data also were included for auto-antibodies to insulin and pancreatic islet cells as possible indicators of pathogenesis and for antibodies to certain viruses that have been implicated as "triggering" agents in IDDM. Medical history of family members was obtained by means of a uniform questionnaire. Identical copies of the dataset were distributed to anyone wishing to participate in the analysis for the IDDM component of GAW5. The multiplex IDDM family dataset is now available on request for further analysis.

Adolescent↗
PubMed1989

Restriction fragment polymorphisms of the HLA-DR, HLA-DQ, and insulin gene regions in IDDM: the GAW5 data.

The primary aim of the insulin-dependent diabetes mellitus (IDDM) component of Genetic Analysis Workshop 5 (GAW5) was to collect and analyze new data on DNA polymorphisms closely linked to the HLA-D region and the insulin gene. The probes and restriction enzymes described here were used by all ten participating labs, and the data from Southern blotting were interpreted and reported according to conventions developed for the Workshop. These DNA data on members of 94 families with two or more IDDM sibs constitute the largest such sample available. The data were used in most of the analyses presented at the Workshop meeting, and are available on request.

Chromosome Mapping↗
PubMed1989

Investigation of genetic markers in patients with Crohn's disease and ulcerative colitis.

Inflammatory bowel diseases (IBD) as Crohn's disease (CD) and ulcerative colitis (UC) are believed to have a genetic basis. Additional factors are supposed to promote the development of IBD. However, apart from a few reports of HLA associations which await confirmation by other groups strong associations to (a) particular genetic marker(s) are still lacking. We here report on previously unobserved associations of CD to MNSS and UC to the immunoglobulin heavy chain allotype Gm 1,-2,10. We suggest that these factors play a role in a wider spectrum of genetic markers for the development of IBD.

Acid Phosphatase↗
PubMed1988

Prospective analysis of islet cell antibodies in children with type 1 (insulin-dependent) diabetes.

The prevalence of islet cell antibodies in children with Type 1 (insulin-dependent) diabetes was determined in a cohort of 678 children. The natural course of islet cell antibodies was followed in 375 children at 1 year, 252 and 135 children after 2 and 3 years respectively. Islet cell antibodies were determined by indirect immunofluorescence on cryostat sections of human pancreas. At diagnosis of diabetes 85% of the children had detectable islet cell antibodies (mean titre 10.4). After 3 years 62% of the children were still islet cell antibody positive (mean titre 2.9) indicating a greater persistence of islet cell antibodies than described in earlier studies. In this large cohort a significant correlation between islet cell antibody prevalence or persistence and sex, age or HLA-DR type was not observed except for a faster loss of islet cell antibodies in very young boys and in patients lacking HLA-DR types 3 and 4. Complement fixing islet cell antibodies correlated with high titre islet cell antibodies. Greater persistence of islet cell antibodies was seen for cases with high antibody titre and in children with diagnosis of diabetes during the first half of the year.

Adolescent↗
PubMed1988

Genetic heterogeneity, modes of inheritance, and risk estimates for a joint study of Caucasians with insulin-dependent diabetes mellitus.

From 11 studies, a total of 1,792 Caucasian probands with insulin-dependent diabetes mellitus (IDDM) are analyzed. Antigen genotype frequencies in patients, transmission from affected parents to affected children, and the relative frequencies of HLA-DR3 and -DR4 homozygous patients all indicate that DR3 predisposes in a "recessive"-like and DR4 in a "dominant"-like or "intermediate" fashion, after allowing for the DR3/DR4 synergistic effect. Removal of DR3 and DR4 reveals an overall protective effect of DR2, predisposing effects of DR1 and DRw8, and a slight protective effect of DR5 and a predisposing effect of DRw6. Analysis of affected-parent-to-affected-child data indicates that a subset of DR2 may predispose. The non-DR3, non-DR4 antigens are not independently associated with DR3 and DR4; the largest effect is a deficiency of DR2, followed by excesses of DR1, DRw8, and DRw6, in DR4 individuals, as compared with DR3 individuals. HLA-B locus distributions on patient haplotypes indicate that only subsets of both DR3 and DR4 are predisposing. The presence or absence of Asp at position 57 of the DQ beta gene, recently implicated in IDDM predisposition, is not by itself sufficient to explain the inheritance of IDDM. At a minimum, the distinguishing features of the DR3-associated and DR4-associated predisposition remain to be identified at the molecular level. Risk estimates for sibs of probands are calculated based on an overall sibling risk of 6%; estimates for those sharing two, one, or zero haplotypes are 12.9%, 4.5%, and 1.8%, respectively. Risk estimates subdivided by the DR type of the proband are also calculated, the highest being 19.2% for sibs sharing two haplotypes with a DR3/DR4 proband.

Adolescent↗
PubMed1988

Association of Crohn's disease with HLA phenotype B44, Cw5.

Genetic influence on the development of Crohn's disease (CD) is commonly accepted. However, proof of definite genetic markers is still pending. Most investigations have focused on HLA antigens, and associations with HLA B12 and HLA A2 have been reported, but the design of these retrospective studies is open to criticism. We have undertaken a consecutive study of 96 patients with CD under well-defined conditions in order to test the hypothesis that CD is associated with particular HLA antigens. Our results identify a significant association of CD with the phenotype HLA B44,Cw5. But since a major proportion of the CD patients do not bear this phenotype, other predisposing genetic factors, which have not yet been defined, may exist in addition to environmental factors.

Adolescent↗
PubMed1988

HLA antigens in ankylosing spondylitis associated with Crohn's disease. Increased frequency of the HLA phenotype B27,B44.

In a consecutive case study 231 patients with Crohn's disease were investigated for ankylosing spondylitis (AS) and HLA-A, B, C, DR antigen association. Eighteen patients (7.8%) had definite AS according to the New York criteria; 13 (72%) were HLA-B27 positive. The phenotype B27,B44 was seen in 8 patients (44%) compared to only 3 (1%) of 300 controls (p less than 10(-7), and 1 (0.5%) of 213 patients with Crohn's disease without AS (p less than 10(-7). We conclude that patients with the phenotype B27,B44 are highly at risk (relative risk = 68.8) for the common manifestation of Crohn's disease and AS.

Adult↗
PubMed1986

HLA-DR effects in a large German IDDM dataset.

DR4 and DR3 are in strongest linkage disequilibrium with IDDM susceptibility genes, and DR1 demonstrates a lesser degree of positive disequilibrium. DR3/DR4 heterozygotes have the highest risk. The DR1 increase occurs almost exclusively in DR4/DR1 heterozygotes, suggesting that DR1 may be in disequilibrium with the same susceptibility gene as DR3. Homozygotes for DR4 and especially DR3 have a higher risk than heterozygotes of either with DRX. GLO-2 is increased in diabetic haplotypes carrying DR4, DR3 or DR1.

Alleles↗