{"id":5375,"date":"2019-09-11T16:13:38","date_gmt":"2019-09-11T14:13:38","guid":{"rendered":"https:\/\/www.resist-cluster.de\/?page_id=5375"},"modified":"2025-12-09T07:48:35","modified_gmt":"2025-12-09T06:48:35","slug":"project-a2","status":"publish","type":"page","link":"https:\/\/www.resist-cluster.de\/en\/research\/project-area-a\/project-a2\/","title":{"rendered":"Project A2"},"content":{"rendered":"

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How can diagnosis be improved to achieve early identification of as many affected individuals as possible?<\/h1><\/div>

Prof. Grimbacher\u00a0 \u00a0|\u00a0 Prof. Witte\u00a0 |\u00a0 Prof. Steinemann <\/a> |\u00a0<\/a>Dr. Atschekzei<\/a><\/p><\/h2><\/div>

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What is this research project about?<\/span><\/h1><\/div>
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The fitness of the immune system and thus the susceptibility to infections shows a Gaussian distribution in the population. The variability of susceptibility to infectious diseases is based on genetic variation.<\/p>\n<\/div>

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What is this research project about?<\/h1><\/div>

The fitness of the immune system is unevenly distributed in the population. On the one hand there are anecdotal reports on the \u201c90-yr-old smoker, who has never been admitted to hospital\u201d; on the other hand there are immunocompromised individuals who would not survive without medical intervention, sometimes necessitating even bone marrow transplantation. These individuals, with a profoundly impaired immune system, manifest with severe and often untypical (e.g. opportunistic) life-threatening infections and a predisposition to (mainly virally-induced) malignancies. In between these two extremes, however, there is a distribution of immune fitness, where patients with recurrent non-life threatening -but repeated or prolonged- infections, represent the majority of cases. In the last decades more than 350 different genes have been found to be mutated in immunodeficiency patients.<\/p>\n<\/div>

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What’s the current status?<\/h1><\/div>
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Depending on the cohort of study, the more than 350 genes associated with primary immunodeficiencies (PID), can only explain about 15-60% of cases. Certainly, there are probably more genes yet to be discovered, however, it is also likely that our search is not deep enough and that the monogenic model is insufficient to fulfill the diagnostic odyssey. Nowadays, Next-generation sequencing (NGS) technologies are routinely used in the clinic to obtain a genetic diagnosis. Most PID patients undergo targeted gene panel (TGP) sequencing or whole exome sequencing (WES), but still, a substantial number of them remain undiagnosed, as it is true for most Mendelian diseases. There may be many reasons for this; first, standard NGS bioinformatics pipelines are not specifically designed to detect copy number alterations (CNAs) or structural variants (SV), and these may be missed. Second, the use of TGP or WES limits the search to the coding part of the genome (2%). Third, other causative or contributing factors, which are excluded with the monogenic model, such as epigenetic profiles and the regulation of gene expression or the gut microbiome, have not been sufficiently studied.<\/p>\n<\/div>

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More patients with immune defects could be registered.<\/p>\n<\/div>

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What are the project goals?<\/h1><\/div>

The main objectives are:<\/p>\n