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Patient with severe immunodeficiency develops functional immune system thanks to single immune stem cell / Findings of significance for stem cell transplants in immunodeficiencies and cancer

A single immune stem cell can take on the role of hundreds of thousands of stem cells and form an essential part of the human immune system. Researchers at the Medical Center - University of Freiburg, together with colleagues from Freiburg, Ulm and Frankfurt, have now demonstrated this in an extremely unusual patient. The patient, who is now 18 years old, is actually unable to produce T immune cells due to a genetic defect. However, an extremely rare random correction of the defect appears to have occurred early on in a single immune stem cell. The result: successor cells of this one T stem cell develop normally and also carry out all necessary immune functions in the long term, such as the destruction of cancer cells or virus-infected cells. Among other things, these findings could help to significantly increase the success of stem cell transplants for cancer or immunodeficiencies. The study was published on August 22, 2020 in the Lancet Group journal EBioMedicine .

"We were extremely surprised by the potential of a single immune stem cell," says study leader Prof. Dr. Stephan Ehl, Medical Director of the Institute of Immunodeficiency at the University of Freiburg and member of the Cluster of Excellence CIBBS - Centre for Integrative Biological Signalling Studies at the Medical Center - University of Freiburg. "It is particularly important that the immune system in our patient has not become fatigued over time and that the immune cells formed are very different despite their common origin from just one immune stem cell. This is crucial for an effective immune defense."

Healthy despite life-threatening illness

The patient Ehl and her colleagues have been following for 13 years has a genetic defect that actually leads to a so-called severe combined immunodeficiency (SCID). Those affected cannot produce T immune cells, which is why even otherwise harmless infections often have serious consequences for them. If left untreated, SCID usually leads to death within the first two years of life. SCID can only be cured by a bone marrow transplant.

This was not necessary for the Freiburg patient. He only received supportive antibodies and was otherwise healthy. "This accidental correction of the genetic defect is a minor miracle in such a serious disease," says Ehl. "At the same time, it shows us that it could be sufficient to repair very few cells in the laboratory using gene therapy or to transfer them as a bone marrow donation." The researchers hope that this will lead to simplified and safer therapeutic procedures.

The team led by immunologist Ehl focuses a lot on such 'borderline' immune systems. "We want to understand how much T-cell immunity is enough to lead a healthy life in the long term. In the best-case scenario, this will enable us to better assess which patients need a new immune system in the form of a stem cell transplant at an early stage," says Ehl.

Original title of the study: Long-term robustness of a T-cell system emerging from somatic rescue of a genetic block in T-cell development
DOI: 10.1016/j.ebiom.2020.102961
Link to the study:https://www.sciencedirect.com/science/article/pii/S2352396420303376

Contact:
Prof. Dr. Stephan Ehl
Medical Director
Institute of Immunodeficiency
Medical Center - University of Freiburg
Phone: 0761 270-77300
stephan.ehl@uniklinik-freiburg.de