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Query: UMLS:C0007570 (celiac disease)
 13,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some decades ago, animal experiments have shown that inbred mice with completely identical genetic characteristics accept transplants between each other without any problem while transplants between individuals of genetically different strains are being rejected after a few days. It was also proven later that with men, genetical factors are responsible for acceptance or rejection of homologous transplants. These genetic factors, although they are called the HLA system, are located on the sixth chromosome. Methods were developed to determine the inherited HLA antigens with the help of antibodies present in the blood serum of pregnant women. The determination is of great importance in preparing transplants organ, especially of kidneys, because chances of successful transplantation are the greater, the better the correspondence of HLA antigens between donor and recipient. Furthermore, there exists growing indication that HLA antigens are coupled or even partly identical with the immune response gene products. These determine whether an individual is more or less suited to develop an immunity against bacterial or viral infections. Finally, there subsist associations of certain HLA antigens and diseases such as gluten enteropathy, myasthenia gravis, multiple sclerosis, diabetes mellitus and many others.
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PMID:[Immunologic HLA-typing. A tool for selection of recipients in transplantation and for detection of disposition to certain diseases (author's transl)]. 33 72

Two new TCRV beta coding region polymorphisms were identified: V beta 6.9a/b and V beta 21.4a/b. In both cases, a single nucleotide difference gives rise to an amino acid exchange. Genomic typing by the PCR/sequence-specific oligonucleotide probing technique was performed to study a possible contribution of these two new polymorphisms in susceptibility to autoimmune diseases. However, there was no association with insulin-dependent diabetes mellitus, rheumatoid arthritis, juvenile rheumatoid arthritis, multiple sclerosis, myasthenia gravis or coeliac disease. On the other hand, significant differences were found between Caucasoid and Oriental populations in frequencies of the V beta 6.9 and V beta 21.4 alleles.
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PMID:Coding region polymorphisms of human T-cell receptor V beta 6.9 and V beta 21.4. 138 40

The associations or linkages between the polymorphisms of the Gm and Km immunoglobulin allotypes and the susceptibility to autoimmune diseases, including diseases with immuno-pathological pathogenesis are reported in this review. These diseases include multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, insulin-dependent diabetes mellitus, Crohn's disease, coeliac disease, Graves' disease, atrophic thyroiditis, Hashimoto's thyroiditis, myasthenia gravis, chronic active hepatitis, alopecia areata, uveitis, vitiligo, Turner's syndrome, glomerular nephritis, Berger's disease and idiopathic dilated cardiomyopathy. Immunoglobulin allotypes are described as well as the statistical methods used to analyse the data.
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PMID:Gm and Km allotypes in autoimmune diseases. 162 73

The finding that diseases such as type I diabetes, coeliac disease and multiple sclerosis are HLA-DQ associated is not easily explained by a simple hypothesis of DQ-restricted, autoreactive T cells, considering the generally marginal role of DQ in restricting responses. Consequently, there have been various attempts to find a differential role for DQ, from presentation of special antigens to preferential stimulation of suppressor cells. Here, Daniel Altmann and colleagues critically assess these proposals and put forward the alternative hypothesis that the effect of DQ on disease susceptibility may result from a special role in shaping the T-cell receptor repertoire.
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PMID:What is the basis for HLA-DQ associations with autoimmune disease? 191 Apr 48

The relationship between increased risk in relatives over population prevalence (lambda R = KR/K) and probability of sharing zero marker alleles identical by descent (ibd) at a linked locus (such as HLA) by an affected relative pair is examined. For a model assuming a single disease-susceptibility locus or group of loci tightly linked to a marker locus, the relationship is remarkably simple and general. Namely, if phi R is the prior probability for the relative pair to share zero marker alleles identical by descent, then P (sharing 0 markers/both relatives are affected) is just phi R/lambda R. Alternatively, lambda AR, the increased risk over population prevalence to a relative R due to a disease locus tightly linked to marker locus A, equals the prior probability that the relative pair share zero A alleles ibd divided by the posterior probability that they share zero alleles ibd, given that they are both affected. For example, for affected sib pairs, P (sharing 0 markers/both sibs are affected) = .25/lambda S. This formula holds true for any number of alleles at the disease locus and for their frequencies, penetrances, and population prevalence. Similar formulas are derived for sharing one and two markers. Application of these formulas to several well-studied HLA-associated diseases yields the following results: For multiple sclerosis, insulin-dependent diabetes mellitus, and coeliac disease, a single-locus model of disease susceptibility is rejected, implying the existence of additional unlinked familial determinants. For all three diseases, the effect of the HLA-linked locus on familiality is minor: for multiple sclerosis, it accounts for only a 2.5-fold increased risk to sibs over the population prevalence, compared to an observed value of 20; for coeliac disease, it accounts for approximately a 5.25-fold increased risk to sibs, while the observed value is on the order of 60; for insulin-dependent diabetes mellitus, it accounts for a 3.42-fold increased risk in sibs, while the observed value is 15. In all cases, the secondary determinants must be outside the HLA region. For tuberculoid leprosy, an unlinked familial determinant is also implicated (increased risk to sibs due to HLA = 1.49; observed value = 2.38). For hemochromatosis and Hodgkin's disease, there is little evidence for HLA-unlinked familial determinants. With this formula, it is also possible to examine the hypothesis of pleiotropy versus linkage dis-equilibrium by comparing lambda AS with the increased risk to sibs due to the associated allele(s).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Assessing the role of HLA-linked and unlinked determinants of disease. 346 4

Statistical features of the method of antigen genotype frequencies among the diseased, for single and multiple disease associations at a locus, will be presented. A methodology to determine when a true intermediate mode of inheritance can be distinguished from strict recessive or additive inheritance will be developed. The effect of sporadics and ascertainment bias on the observed antigen genotype frequencies will be investigated. Data on ankylosing spondylitis, multiple sclerosis and dermatitis herpetiformis are very close to expectations for an additive (or dominant) mode of inheritance for the HLA-linked disease-predisposing gene, and data on hemochromatosis, insulin dependent diabetes mellitus and celiac disease are close to recessive expectations. If an intermediate model does apply in any of these cases, it must be an intermediate model that is fairly close to a strict recessive or dominant model; as appropriate. DR data for insulin dependent diabetes mellitus (IDDM) strongly indicate that there are two separate "disease" alleles, which exhibit negative complementation, predisposing individuals to IDDM, where the mode of inheritance of the "disease" alleles considered separately is close to recessive. In general, this method cannot rule out the existence of sporadics or a second disease-predisposing gene, when the penetrance values over the two disease-predisposing genes are strictly additive, for diseases showing agreement with additive (or dominant) modes of inheritance.
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PMID:Investigation of the mode of inheritance of the HLA associated diseases by the method of antigen genotype frequencies among diseased individuals. 640 4

An iteration procedure is outlined which uses HLA haplotype sharing data from sib pairs in which both sibs have the disease of interest. The procedure allows estimation of the degree of dominance of the HLA linked 'disease' allele, and its frequency in the population, for intermediate models where it is assumed that individuals who do not have at least one copy of the 'disease' allele do not contract the disease. Parameter estimates from sib-pair data on multiple sclerosis, insulin dependent diabetes mellitus, haemochromatosis, coeliac disease juvenile rheumatoid arthritis, and Graves' and Hashimoto's diseases are given.
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PMID:The affected sib method. II. The intermediate model. 668 9

A test of linkage that is exact even in small samples is developed for multiple case families, together with large-sample theory for estimation and supplementary tests. Hemochromatosis, insulin-dependent diabetes, and celiac disease are compatible with an intermediate model biased toward recessivity on the penetrance scale, whereas multiple sclerosis favors dominance and unlinked modifiers. Alternatives to the model are complex, and comparison of affected sib pairs with larger sets of relatives provides no critical evidence of epistasis. Problems of sampling and inference are discussed.
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PMID:An exact linkage test for multiple case families. 688 87

The genes of the human leukocyte antigen (HLA) region, the major histocompatibility complex (MHC) of humans, control a variety of functions involved in immune response and influence susceptibility to over 40 diseases. Theoretical studies in the development of models to determine the modes of inheritance of the HLA-associated diseases have led to a better understanding of the inheritance patterns in insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, hemochromatosis, celiac disease, and others. It is now clear that many of the HLA-associated diseases involve heterogeneity in their HLA components, as well as non-HLA genetic factors. This review is presented using HLA-associated diseases, and in particular IDDM, as the example of interest, but the observations and techniques presented have direct relevance to the study of all human diseases with a complex genetic component. Three methods for localizing disease-predisposing genes are presented: (1) association studies, including population, family, and relative predispositional effects, (2) affected sib pair and other affected-relative methods, and (3) lod score analysis. A variety of complementary methods for studying the mode(s) of inheritance of the alleles at the disease-predisposing locus and for identifying the alleles and amino acids directly involved in the disease process also are presented.
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PMID:HLA disease associations: models for the study of complex human genetic disorders. 759 90

GM and KM immunoglobulin (Ig) allotypes and their interactions with HLA antigens have been analyzed in various autoimmune diseases: multiple sclerosis, rheumatoid arthritis, insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus, coeliac disease, Crohn's disease, Graves' disease, atrophic thyroiditis, Hashimoto's thyroiditis, myasthenia gravis, chronic active hepatitis, alopecia areata, uveitis, vitiligo, Turner's syndrome, glomerular nephritis, Berger's disease and idiopathic dilated cardiomyopathy. This review reports published results about associations or linkages, as well as the origins of the populations, the numbers of patients and controls tested. The possible role of Ig polymorphisms in the physiopathology of autoimmune diseases is discussed. Ig allotypes and statistical methods used to analyse the HLA and Ig data are also described.
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PMID:Immunoglobulin allotypes (GM and KM) and their interactions with HLA antigens in autoimmune diseases: a review. 878 16


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