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Differential expression of predisposing HLA-DQ2.5 alleles in DR5/DR7 celiac disease patients affects the pathological immune response to gluten
- Source :
- Scientific reports (Nature Publishing Group) 10 (2020). doi:10.1038/s41598-020-73907-2, info:cnr-pdr/source/autori:Pisapia L.; Picascia S.; Farina F.; Barba P.; Gianfrani C.; Del Pozzo G./titolo:Differential expression of predisposing HLA-DQ2.5 alleles in DR5%2FDR7 celiac disease patients affects the pathological immune response to gluten/doi:10.1038%2Fs41598-020-73907-2/rivista:Scientific reports (Nature Publishing Group)/anno:2020/pagina_da:/pagina_a:/intervallo_pagine:/volume:10, Scientific Reports, Scientific Reports, Vol 10, Iss 1, Pp 1-8 (2020)
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group, London , Regno Unito, 2020.
-
Abstract
- The DR5-DQ7/DR7-DQ2 genotype is very frequent among patients affected by celiac disease (CD), in Europe. This genotype, associated to high risk of CD, carries the HLA-DQA1*05 and HLA-DQB1*02 predisposing alleles, in trans configuration. The alleles encode the DQ2.5 heterodimer responsible of gluten peptide presentation on the surface of antigen-presenting cells (APCs), and consequent pathogenic CD4+ T cell activation. We demonstrated that DR5/DR7 APCs induce an anti-gluten CD4+ T cell response, of comparable intensity to that observed with APCs carrying DR1/DR3 genotype, which risk alleles are in cis configuration. In addition, we showed that DR5/DR7 APCs from celiac patients stimulated an effector CD4+ T cell response higher with respect to that induced by DR5/DR7 APCs from healthy subjects. To explain these findings, we assessed the DQ2.5 RNA and protein quantity. We showed that the expression of DQA1*05 and DQB1*02 risk alleles is much higher than the expression of non-CD-associated alleles, in agreement with the previous results obtained with DR1/DR3 genotype. The differential expression of transcripts influences the quantity of DQα1*05 and DQβ1*02 chains and, as consequence, the cell surface density of DQ2.5 heterodimers. Moreover, both RNA and proteins, are more abundant in APCs from celiac patients than controls. Finally, to unravel the mechanism regulating the expression of predisposing DQA1*05 and DQB1*02 alleles, we quantified the new synthetized RNA and found that the differential expression is explained by their transcription rate. Our results confirmed that the strength of antigen-specific CD4+ T cell response is mainly determined by the amount of gluten in the diet and provided a new possible approach for a personalized diagnosis and for risk stratification.
- Subjects :
- CD4-Positive T-Lymphocytes
0301 basic medicine
Glutens
T cell
Immunology
Cell
lcsh:Medicine
Antigen-Presenting Cells
Gene Expression
autoimmunità
Biology
Article
03 medical and health sciences
0302 clinical medicine
Immune system
HLA-DQ Antigens
Genotype
Gene expression
Genetics
medicine
Humans
Genetic Predisposition to Disease
Allele
lcsh:Science
Receptor
Alleles
B-Lymphocytes
Multidisciplinary
celiachia
lcsh:R
HLA-DQ2
nutritional and metabolic diseases
HLA-DR Antigens
HLA
Celiac Disease
Receptors, TNF-Related Apoptosis-Inducing Ligand
030104 developmental biology
medicine.anatomical_structure
lcsh:Q
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Scientific reports (Nature Publishing Group) 10 (2020). doi:10.1038/s41598-020-73907-2, info:cnr-pdr/source/autori:Pisapia L.; Picascia S.; Farina F.; Barba P.; Gianfrani C.; Del Pozzo G./titolo:Differential expression of predisposing HLA-DQ2.5 alleles in DR5%2FDR7 celiac disease patients affects the pathological immune response to gluten/doi:10.1038%2Fs41598-020-73907-2/rivista:Scientific reports (Nature Publishing Group)/anno:2020/pagina_da:/pagina_a:/intervallo_pagine:/volume:10, Scientific Reports, Scientific Reports, Vol 10, Iss 1, Pp 1-8 (2020)
- Accession number :
- edsair.doi.dedup.....2103bba1c209eb0ec055e1ab1a24e771