DEEP IMMUNOLOGIC PROFILING OF TRISOMY 8 ASSOCIATED AUTOINFLAMMATORY DISEASE (TRIAD)

ABSTRACT: Trisomy 8 mosaicism is a cytogenetic abnormality often seen in hematologic malignancies but also associated with inflammatory disease. We characterized individuals with trisomy 8 mosaicism and inflammatory symptoms in the absence of malignancy. Subjects presented with recurrent episodes of fever and oral, genital, and gastrointestinal ulcers in childhood. We propose calling this distinct autoinflammatory disease trisomy 8-associated autoinflammatory disease or TRIAD. CITE-seq in subjects with 6 subjects with trisomy 8 and inflammatory disease and 3 healthy controls revealed expansion of classical CD14+ monocytes with an IL-1b and type 1 IFN signature. We identified trisomy and disomy cells in trisomy 8 subjects using expression levels of genes on chromosome 8. We found that myeloid cells had high percentage trisomy 8 cells, and trisomy CD14+ monocytes had higher expression of type I IFN, type II IFN, and IL-1b signaling pathways compared to healthy controls. However, among lymphocytes, naïve T lymphocytes had high levels of trisomy 8 cells, while their effector/memory counterparts had low levels. Trisomy 8 memory CD8+ T cell had lower expression of cytotoxic genes compared to disomy cells and healthy controls. Significantly fewer trisomy 8 cells were noted among expanded CD8+ memory T clones compared to unexpanded clones.

ORGANISM(S): Homo sapiens

PROVIDER: GSE272583 | GEO | 2026/09/17

REPOSITORIES: GEO