Polyclonal selection of immune checkpoint mutations in thyroid autoimmunity - PubMed
5 hours ago
- #somatic evolution
- #immune checkpoint mutations
- #autoimmune thyroid disease
- Study used whole-exome and targeted NanoSeq to find driver mutations in autoimmune thyroid disease.
- Identified B cell clones with loss-of-function mutations in TNFRSF14 (HVEM) and CD274 (PD-L1), and other immune genes.
- In inflamed biopsies, tens to hundreds of independent immune checkpoint mutant clones were detected.
- Mutations localized to B cells, some confirmed as self-reactive, with clones having multiple hits, including TNFRSF14 biallelic loss and up to 4-6 driver mutations.
- Each clone is small (<1% of cells), but collectively they represent a significant fraction of B cells with driver mutations.
- Findings support somatic mutations enabling immune escape via polyclonal somatic evolution in autoimmunity.