| 1. |
- Popat, S, et al.
(författare)
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Genome screening of coeliac disease
- 2002
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 39:5, s. 328-331
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Popat, S, et al.
(författare)
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Variation in the CTLA4/CD28 gene region confers an increased risk of coeliac disease
- 2002
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Ingår i: Annals of Human Genetics. - : Wiley. - 1469-1809 .- 0003-4800. ; 66:2, s. 125-137
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Tidskriftsartikel (refereegranskat)abstract
- Susceptibility to coeliae disease involves HLA and non-HLA-linked genes. The CTLA4/CD28 gene region encodes immune regulatory T-cell surface molecules and is a strong candidate as a susceptibility locus. We evaluated CTLA4/CD28 in coeliac disease by genetic linkage and association and combined Our findings with published studies through a meta-analysis. 116 multiplex families were genotyped across CTLA4/CD28 using eight markers. The contribution of CTLA4/CD28 to coeliac disease was assessed by non-parametric linkage and association analyses. Seven studies were identified that had evaluated the relationship between CTLA4/CD28 and coeliac disease and a pooled analysis of data undertaken. In our study there was evidence for a relationship between variation in the CTLA4/CD28 region and coeliae disease by linkage and association analyses. However. the findings did not attain formal statistical significance (p=0.004 and 0.039. respectively). Pooling findings with published results showed significant evidence for linkage (504 families) and association (910 families) : p values. 0.0001 and 0.0014 at D2S2214. respectively. and 0.0008 and 0.0006 at D2S116, respectively. These findings suggest that variation in the CD28/CTLA4 gene region is a determinant of coeliac disease susceptibility. Dissecting the sequence variation underlying this relationship will depend on further analyses utilising denser sets of markers.
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| 3. |
- Roth, Bodil, et al.
(författare)
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Biochemical and immuno-pathological aspects of tissue transglutaminase in coeliac disease
- 2003
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 36:4, s. 221-226
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Tidskriftsartikel (refereegranskat)abstract
- Tissue transglutaminase (tTg) has been identified as the major autoantigen in coeliac disease (CD). ELISA methods have been developed for measuring the autoantibody. There are divergent reports on the effects of calcium on the antibody binding to tTg. Furthermore, zinc is a potent inhibitor of tTg. To better understand the role of transglutaminase in CD, we have studied the stability of commercial tTG, the effect of CD serum on tTg-activity and the effects of calcium and zinc on the antibody binding. The inclusion of calcium during the coating of the ELISA plates significantly increases the binding of the antibody, while zinc at physiological concentrations inhibits the binding. Moreover, our results show that commercial guinea pig liver Tg treated with calcium contains at least four major antigenic molecules and is a labile enzyme, which is degraded rapidly by contaminating proteases. Human serum contains anti-proteases that protect the enzyme. Probably, the labile character of commercial tTG explains the divergent reports on the effects of calcium on antibody binding. Finally, antibodies in serum from a CD patient do not seem to inhibit tTg activity. Hypothetically, low, intestinal Zn2+ -levels facilitate Ca2+ -activation of tTg, which deamidates gliadin. A complex between tTg and modified gliadin forms the antigen and triggers the immune reaction leading to manifest CD. Hypozincaemia secondary to villous atrophy aggravates the induced disease.
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| 4. |
- Sjöberg, Klas, et al.
(författare)
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Factor XIII and tissue transglutaminase antibodies in coeliac and inflammatory bowel disease.
- 2002
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 35:5, s. 357-364
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Tidskriftsartikel (refereegranskat)abstract
- issue transglutaminase (tTg) has been identified as an autoantigen in coeliac disease (CD). There is a marked homology between different forms of transglutaminase, such as tTg and coagulation factor XIII. We compared titres of both IgA- and IgG-antibodies against these two antigens in 20 CD patients, 20 endomysial antibody (EMA)-negative controls and a group with inflammatory bowel disease (34 with Crohn's disease and 23 with ulcerative colitis). IgA-antibodies against tTg correlated with EMA titres and had high sensitivity and specificity in screening for CD. Only in two CD patients were high titres found of IgA-antibodies against factor XIII, non-reactive with tTg. Both lacked bleeding tendency. The presence of IgG-antibodies against tTg, in contrast, had low sensitivity and specificity in screening for CD and were frequently seen in inflammatory bowel disease. Similarly, factor XIII IgG-antibodies displayed a non-specific pattern with modestly elevated titres in patients with Crohn's disease and in both EMA-negative and positive patients. Despite a marked homology with tTg, the occurrence of high titre IgA-antibodies against factor XIII is infrequent in CD, but may--when present--be the result of epitope spreading. The presence of IgG-antibodies in CD and inflammatory bowel disease illustrates the complexity of autoantibody reactions in gastrointestinal disease.
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| 5. |
- Sjöberg, Klas, et al.
(författare)
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Screening för celiaki kan vara motiverad i högriskgrupper
- 2004
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Ingår i: Läkartidningen. - 0023-7205. ; 101:48, s. 6-3918
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Coeliac disease is widespread and occurs in 0.5-1 per cent of the population. Most sufferers show atypical symptoms and might well remain undiagnosed. Endomysial or human transglutaminase autoantibody levels of type IgA can be recommended as screening instruments combined with s-IgA for exclusion of such deficiency. In contrast, there is a high frequency of false-positive IgA gliadin antibody test results, especially where coeliac disease is common, as in chronic liver disease, diabetes, thyroid disease and conditions with chromosomal aberrations (Down syndrome and Turner syndrome). Despite this, gliadin antibodies of type IgA are still the best marker for coeliac disease in children under two years of age. While mass screening is not to be recommended, case finding is worthwhile in well defined risk groups, i.e. in cohorts with autoimmune disease or chromosomal aberrations or in relatives to anyone with coeliac disease. A positive biopsy is still the gold standard for diagnosis.
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| 6. |
- Sjöberg, Klas
(författare)
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Serologic Markers in Screening for Coeliac Disease, Clinical significance and immunogenetic basis
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The prevalence of coeliac disease (CD) was initially estimated to 1/1537. Based on serial analysis [GA and endomysial antibodies (EMA)], the prevalence was 6/1970 (0.30%). In autoimmune chronic hepatitis 5.4% and in IDDM 2.6% had CD, why regular screening for CD in these conditions seems motivated. The frequency of IgA-GA positivity was increased in alcoholic liver disease, PBC, primary sclerosing cholangitis, chronic hepatitis, and hepatitis C, as well as in IDDM, NIDDM, and in secondary diabetes to 11-24% compared with blood donors (5%). Consequently, investigation in GA-positive individuals with suspicion of CD should be completed with EMA/tTg. CD was correlated with HLA-DR3 and DQ2, whereas DQ1, DQ7, DR1, DR4 and DR5 were all inversely correlated. 79% of GA-positive but healthy individuals had DQ1, which would be expected to confer protection. The findings suggest GA-positivity to be independent of the HLA genotype in CD. From 848 IDDM patients 16 high titre GA patients were selected and compared with 37 matched low titre patients. Chronic thyroiditis, thyroid peroxidase and factor XIII IgA antibody positivity and HLA DRB1*13 were correlated with GA-positivity, while tissue transglutaminase IgG titres were inversely correlated. A tissue transglutaminase (tTg) ELISA method has been developed for CD-screening. The possibility to replace tTg by recombinant factor XIII was investigated. A patient with CD and antibodies against the active site of factor XIII is described. In sera from 20 patients with EMA and 20 controls no correlation between tTg and factor XIII was observed. Determination of antibody titres against factor XIII is not appropriate to use in screening for CD.
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| 7. |
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