By linking antibodies to certain diseases, researchers at UC Santa Barbara have found a way to uncover and confirm environmental triggers
\nBy cross referencing the amino acid sequence of peptides strongly associated with illnesses with a library of known peptides, researchers may be able to map antigens with identical sequences to their environment, thus uncovering and confirming environmental triggers for diseases such as Type-1 diabetes, schizophrenia, and autism.
\nYou may be sensitive to gluten, but you\u2019re not sure. Perhaps you can\u2019t put your finger on a recurring malaise, and your doctor is at a loss to figure it out. A diagnostic method recently developed by UC Santa Barbara professor Patrick Daugherty can reveal \u2014 on a molecular level \u2014 the factors behind conditions thought to have environmental triggers. By decoding an individual\u2019s immune system, this elegant and accurate method can demystify, diagnose and provide further insight into conditions like celiac disease, multiple sclerosis, pre-eclampsia and schizophrenia.<\/p>\n
‘We have two goals,’ said Daugherty, a researcher with the Department of Chemical Engineering at UCSB and the campus\u2019s Center for BioEngineering. ‘We want to identify diagnostic tests for diseases where there are no blood diagnostics \u2026 and we want to figure out what might have given rise to these diseases.’<\/p>\n
The process works by mining an individual\u2019s immunological memory \u2014 a veritable catalogue of the pathogens and antigens encountered by his or her immune system.<\/p>\n
‘Every time you encounter a pathogen, you mount an immune response,’ said Daugherty. The response comes in the form of antibodies that are specific to the antigens \u2014 molecular, microbial, chemical \u2014 your body is resisting, and the formation of ‘memory cells’ that are activated by subsequent encounters with the antigen. Responses can vary, from minor reactions \u2014 a cough, or a sneeze \u2014 to serious autoimmune diseases in which the body turns against its own tissues and its immune system responds by destroying them, such as in the case of Type 1 diabetes and celiac disease.<\/p>\n
‘The trick is to determine which antibodies are linked to specific diseases,’ said Daugherty. Celiac disease sufferers, for example, will have certain antibodies in their blood that bind to specific peptides \u2014 short chains of amino acids \u2014 present in wheat, barley and rye. These peptides are the gluten that is the root of allergies and sensitivities in some people. Like a lock and key, these antibodies \u2014 the locks \u2014 bind only to certain sequences of amino acids that comprise the peptides \u2014 the keys.<\/p>\n
‘People with celiac disease have two particular antibody types in their blood, which have proved to be enormously useful for diagnosis,’ said Daugherty.<\/p>\n
However, sheer variety and number of antibodies present in a person\u2019s blood at any given time has been a challenge for researchers trying to link specific illnesses with specific antibody molecules. One antigen can stimulate the production of many antibodies in response. What\u2019s more, each individual\u2019s antibodies to even the same antigen differ slightly in their form. The idea of using molecular separation to find the disease antibodies has been around for over 20 years, said Daugherty, but no one had figured quite how to sift through the vast amount of molecules.<\/p>\n
To sort through perhaps tens of thousands of antibody molecules present in a person\u2019s blood, the research team \u2014 including John T. Ballew from UCSB\u2019s Biomolecular Science and Engineering graduate program, now a postdoctoral associate with the Koch Institute for Integrative Cancer Research at MIT \u2014 mixed a sample of a subject\u2019s blood, which contains the antibody molecules, with a vast number of different peptides (about 10 billion).<\/p>\n
‘All the keys associate with their preferred lock,’ said Daugherty. ‘The peptides that can bind to an antibody, do so.’ The researchers then pull out the disease-bound pairs, in a process that progressively decreases the number of antibodies-peptide pairs that are most unique to a particular disease. Repeated with subsequent patients who may have the same symptoms, phenotypes or genetic dispositions, continues to whittle down the size of the peptide pool. Further in vitro evolution of the best draft peptides can identify the particular sequence of amino acid keys that fit into the antibody locks. This sequence can be used to confirm the antibodies in question as the biomarkers specifically associated with the disease.<\/p>\n
‘The diagnostic performance of the reagents generated with this approach is excellent,’ said Daugherty. ‘We can discover biomarkers with as little as a drop of blood, and the peptides discovered can be adapted into preferred low cost testing platforms widely used in clinical practice.’<\/p>\n
The amino acid sequence of the evolved peptides, when cross-referenced with a database of known proteins, can identify the antigens (that contain the same peptide sequence). This, in turn, can then yield clues into what factors in the patient\u2019s environment may have contributed to the disease. The process may be used to gain insight on diseases that are thought to have environmental triggers, including Type-1 diabetes, autism, schizophrenia\/bipolar disorder, Crohn\u2019s disease, Parkinson\u2019s disease, and perhaps even Alzheimers disease. In cases, such as Graves\u2019 disease, where an antibody is identified as the cause (as opposed to simply an indicator) knowing the antibody\u2019s structure can lead to more effective therapies.<\/p>\n
‘If you can get rid of the antibody, you can treat the disease,’ said Daugherty. ‘By finding these keys, you can block the antibody.’\nUniversity of California \u2013 Santa Barbara<\/link>\n","protected":false},"excerpt":{"rendered":"
By linking antibodies to certain diseases, researchers at UC Santa Barbara have found a way to uncover and confirm environmental triggers By cross referencing the amino acid sequence of peptides strongly associated with illnesses with a library of known peptides, researchers may be able to map antigens with identical sequences to their environment, thus uncovering […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[35],"tags":[],"class_list":["post-1727","post","type-post","status-publish","format-standard","hentry","category-e-news"],"_links":{"self":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/1727"}],"collection":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/comments?post=1727"}],"version-history":[{"count":0,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/1727\/revisions"}],"wp:attachment":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/media?parent=1727"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/categories?post=1727"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/tags?post=1727"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}