Nature’s Accidental Gene Edit Cures a Chronic Infection

Epstein-Barr virus (EBV) is a pervasive pathogen usually kept in check by CD8 T cells, the immune system’s specialist hunters. However, individuals with a rare genetic defect in a protein called CD137 struggle to control this virus, leading to chronic illness. Scientists recently investigated a patient with this specific deficiency who had received a stem cell transplant from her brother. Unfortunately, the brother carried the same genetic flaw, meaning the transplant initially failed to suppress the virus.

Remarkably, the patient’s condition later improved spontaneously. Upon analysing her blood, researchers discovered that 'somatic reversion' had occurred. This means that within the donor cells living inside the patient, natural mutations took place that accidentally fixed the broken gene. These self-corrected cells were not just rare anomalies; they multiplied rapidly, eventually constituting 20 per cent of the CD8 T cells in her bloodstream.

Using single-cell RNA sequencing, the team confirmed these 'revertant' clones originated from the donor’s cells post-transplant. This restoration of function allowed the immune system to finally mount a strong defence against EBV. This is the first recorded instance of such a phenomenon in CD137 deficiency, offering a promising roadmap for future gene therapies to treat similar inborn errors of immunity.