Progressive B Cell Loss in Revertant X-SCID.
Connie H LinHye Sun KuehnTimothy J ThaulandChristine M LeeSuk See De RavinHarry L MalechTimothy J KeyesAstraea JagerKara L DavisMaria I Garcia-LloretSergio D RosenzweigManish J ButtePublished in: Journal of clinical immunology (2020)
We report the case of a patient with X-linked severe combined immunodeficiency (X-SCID) who survived for over 20 years without hematopoietic stem cell transplantation (HSCT) because of a somatic reversion mutation. An important feature of this rare case included the strategy to validate the pathogenicity of a variant of the IL2RG gene when the T and B cell lineages comprised only revertant cells. We studied the X-inactivation of sorted T cells from the mother to show that the pathogenic variant was indeed the cause of his SCID. One interesting feature was a progressive loss of B cells over 20 years. CyTOF (cytometry time of flight) analysis of bone marrow offered a potential explanation of the B cell failure, with expansions of progenitor populations that suggest a developmental block. Another interesting feature was that the patient bore extensive granulomatous disease and skin cancers that contained T cells, despite severe T cell lymphopenia in the blood. Finally, the patient had a few hundred T cells on presentation but his TCRs comprised a very limited repertoire, supporting the important conclusion that repertoire size trumps numbers of T cells.
Keyphrases
- case report
- rare case
- bone marrow
- machine learning
- multiple sclerosis
- deep learning
- induced apoptosis
- copy number
- early onset
- single cell
- cell death
- cell cycle arrest
- staphylococcus aureus
- neural network
- genome wide
- oxidative stress
- signaling pathway
- gene expression
- soft tissue
- cell proliferation
- transcription factor
- risk assessment
- climate change
- idiopathic pulmonary fibrosis
- systemic sclerosis