T Cell Transcriptome in Chromosome 22q11.2 Deletion Syndrome

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Chromosome 22q11.2 deletion syndrome (22qDS) presents with varied phenotypes, partly due to T cell lymphopenia linked to thymic hypoplasia.
• The genetic basis for T cell lymphopenia in 22qDS remains unclear, with no known correlation to genotype or deletion size.

Purpose of the Study:

• To investigate differential gene expression in T cells from individuals with and without 22qDS.
• To compare gene expression between 22qDS patients with low versus normal T cell counts.

Main Methods:

• Peripheral blood T cells were isolated from 22qDS patients (n=13) and healthy controls (n=6), aged 5-8 years.
• RNA sequencing was performed to identify differentially expressed genes.
• Gene expression was analyzed between 22qDS subgroups: low T cell count (n=7) and normal T cell count (n=6).

Main Results:

• 360 genes were differentially expressed between 22qDS patients and controls (q < 0.05).
• 94 genes were differentially expressed between 22qDS patients with low versus normal T cell counts (q < 0.05).
• Twenty-nine genes showed strong correlation (R ≥ 0.8) with T cell counts and specific immune markers (CD3, CD4, CD8, CD45RA+CD4).
• Enriched pathways suggest impaired T cell communication with the innate immune system in 22qDS, notably the liver X receptor/retinoid X receptor pathway.

Conclusions:

• Significant gene expression differences exist in T cells of 22qDS patients compared to controls.
• Distinct gene expression profiles are observed in 22qDS patients with low T cell counts.
• Altered T cell immune responses and communication pathways, particularly the LXR/RXR pathway, may contribute to 22qDS pathophysiology.