Celiac disease (CD) involves intolerance to gluten and, consequently, suffering chronic illness in the small intestine. It is a genetic disorder, the immunological indications of which can be traced in the human body prior to the everyday activities of future sufferers being affected. For example, persons with genetic antecedents for CD develop antibodies against the gene tTG (the enzyme known as tissue transglutaminase), even before the illness becomes active, due to a cell reaction against gluten.
The clinical symptoms of CD appear only in the final stages of the disease. This is why it is important to find the genes linked to it, thus facilitating an early diagnosis, as well as fighting against CD before it becomes an active illness. In effect, biologist Ms Ainara Castellanos has opened a door to the elucidation of this: her research was aimed at identifying genes that may have a functional involvement in the CD, developing a tool which, amongst other things, looked at the changes in gene expression. For example, she was able to verify that the gene known as UBD may be linked to CD. Her thesis, defended at the University of the Basque Country (UPV-EHU), is entitled, Functional players in celiac disease: identification and genetic association.
In order to undertake her research, Ms Castellanos used intestinal biopsies at the Hospital de Cruces (in Barakaldo, near the Basque city of Bilbao), drawing up a strategy that crossed data on gene levels of expression gathered from these biopsies, information about the anatomical regions closely linked to CD, and various bioinformatic instruments.
The research undertaken in this thesis confirmed that this tool, which takes levels of expression of the genes into account, is useful in identifying those which are especially susceptible to CD. In fact, thanks to the work, Ms Castellanos was able to distinguish, in the anatomical regions closely linked to CD, a number of genes subjected to alterations in their expression caused by gliadine (a protein that forms part of gluten), and she verified that these genes are candidates for being functionally involved with CD.
Besides this, based on information obtained from intestinal biopsies of the celiac patients, she was able to undertake an analysis and a general description of the alterations in expression caused by gliadine in the intestinal mucous. Given all this, Ms Castellanos concluded that, in those cases in which there is CD, malfunctions in intercellular communication, in intracellular signalling, in ubiquitine proteins and in a number of other networks are produced. Thus, she confirmed that CD is a complex and multifactorial illness. Moreover, on describing the changes happening with the levels of expression, she has provided guidelines on understanding how CD develops and found new factors which influence this progress of the disease.
Amongst the networks mentioned previously, Ms Castellanos stressed the ubiquitine proteins, concretely ubiquitine D (UBD). An over-expression of UBD in the intestinal biopsies of the celiac patients and, in relation to this, a genetic variant or polymorphism linked to CD. As she explains in her thesis, this polymorphism could precisely be the inductor of this over-expression. Ms Castellanos stressed that the same could happen with other genes, candidates for being involved in CD. As a consequence, the example of UBD has confirmed that the observation of the genetic expressions can help in finding those genes which, while being unknown as yet, are linked to the onset of CD.
Ms Ainara Castellanos Rubio (Portugalete, 1982) is a Biology graduate. She defended her PhD thesis in the Department of Genetics, Physical Anthropology and Animal Physiology of the Science and Technology Faculty of the UPV/EHU. She undertook her research under the direction of José Ramón Bilbao Catalá (from the Department of Genetics, Physical Anthropology and Animal Physiology) and Luis Castaño González (Department of Paediatrics); both lecturers at Teaching Unit of the Cruces Hospital. She carried out her thesis mainly at the Immunogenetic Laboratory of the Hospital’s Research Unit, and also spent four months at the University of Tamper, Finland, in the Celiac Diseases Research Group. Ms Castellanos is currently a postgraduate researcher at Columbia University (USA), in Professor Sankar Ghosh’s laboratory at the Department of Microbiology and Immunology.
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