Celiac disease: caught between a rock and a hard place.
ABSTRACT Celiac disease (CD) is an intestinal disorder caused by an intolerance to gluten, proteins in wheat. CD is an HLA-associated disease: virtually all patients express HLA-DQ2 or HLA-DQ8. Recent work has shown that these disease-predisposing HLA-DQ molecules bind enzymatically modified gluten peptides and these HLA-DQ peptide complexes trigger inflammatory T-cell responses in the small intestine that lead to disease. In addition, gluten induces innate immune responses that contribute to the tissue damage that is characteristic for CD. Thus, CD patients are caught between a rock and a hard place: the disease is caused by a combination of adaptive and innate immune responses that both are triggered by gluten. These findings explain the disease-inducing properties of gluten and provide valuable clues for the development of alternative treatment modalities for patients. They also may be of relevance for our understanding of other multifactorial disorders including IBD and HLA-associated autoimmune diseases.
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ABSTRACT: Stable isotope analysis in the reconstruction of human palaeodiets can yield clues to early human subsistence strategies, origins and history of farming and pastoralist societies, and intra- and intergroup social differentiation. In the last 10 years, the method has been extended to the pathological investigation. Stable isotope analysis to better understand a diet-related disease: celiac disease in ancient human bones was carried out. To do this, we analyzed the nitrogen and carbon isotopic composition of human (n = 37) and faunal (n = 8) bone remains from the archaeological site of Cosa at Ansedonia, on the Tyrrhenian coast near Orbetello (Tuscany), including the skeletal remains of a young woman (late 1st century–early 2nd century Common Era [CE]) with morphological and genetic features suggestive of celiac disease. We compared the young woman's isotopic data with those of other individuals recovered at the same site but from two later time periods (6th century CE; 11–12th century CE) and with literature data from other Italian archaeological sites dating to the same period. Her collagen δ13C and δ15N values differed from those of the samples at the same site, and from most but not all of the contemporary sites. Although the woman's diet appears distinct, chronic malnutrition resulting from severe malabsorption of essential nutrients due to celiac disease may have affected the isotopic composition of her bone collagen. Am J Phys Anthropol, 2014. © 2014 Wiley Periodicals, Inc.American Journal of Physical Anthropology 04/2014; · 2.48 Impact Factor
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ABSTRACT: Rheumatoid arthritis (RA) is a destructive autoimmune disease that mainly affects synovial joints. RA patients can be subdivided in two distinct disease subsets based on the presence of anti-citrullinated protein antibodies (ACPA). These two disease phenotypes are associated with different environmental and genetic risk factors and clinical parameters. The HLA class II locus is the most important risk factor for ACPA-positive RA (ACPA+ RA). ACPA can be found up to 10 years before diagnosis and can be used as a predictive biomarker. During progression from breaking tolerance to a citrullinated protein to ACPA+ RA, the ACPA response matures. Recent work implicates the HLA class II locus as a risk factor in the progression from ACPA positivity to ACPA+ RA. We now propose that this locus directly influences the maturation of the ACPA response, most likely via antigen-specific T-cells providing help to ACPA-producing B-cells allowing for maturation of the citrullinated protein-specific autoantibody response. We present and discuss several models and underlying data, including antibody cross-reactivity, molecular mimicry, and neo-antigen formation, that could explain the HLA-RA connection.Annals of medicine 05/2014; · 3.52 Impact Factor