Transcriptome analysis of T cells in chromosome 22q11.2 deletion syndrome
Saturday, March 3, 2018
South Hall A2 (Convention Center)
Nikita Raje, MD MBBS, Shui Qing Ye, MD, PhD, Daniel P Heruth, PhD, Nicole M Gigliotti, BS, Hongying Dai, PhD, Min Xiong, PhD, Marcia A. Chan, PhD

RATIONALE: T cell lymphopenia in chromosome 22q11.2 deletion syndrome (22qDS) is related to varying degrees of thymic hypoplasia. No phenotype correlation with genotype or deletion size is known for lymphopenia. We hypothesized that T-cell transcriptome is different in 22qDS from healthy children and this difference is associated with lymphocyte counts and function leading to clinically diverse phenotypes.

METHODS: After IRB approval, peripheral blood from a convenience sample of participants ages 5-8 years (5:22qDS and 4: healthy controls) was collected. Standard immune testing was performed. RNA sequencing was completed on isolated T cells using Illumina’s TruSeq technology. Bioinformatic analyses were implemented using Tuxedo Suite & String Tie pipelines. Differential expression between the two groups was determined using parametric ANOVA test and nonparametric Kruskal-Wallis test. Differentially expressed genes (p-value <0.0001) were submitted for Ingenuity Pathway Analysis. The Spearman correlation between RNA and CD3 counts were calculated using SAS (9.4, Cary, NC) (p-value<0.05).

RESULTS: A total of 241 genes including one noncoding RNA were differentially expressed between T cells of 22qDS and healthy controls. The top 20 biological processes with differential expression included 48 immune response, 15 positive regulation of immune system process, 11 regulation of lymphocyte activation, and 10 regulation of T cell activation genes. An inverse relationship between T cells and the expression of inflammatory cytokines (IFNγ, IL-1β, CCL3, CXCL8) was noted.

CONCLUSIONS: Differences in the T-cell transcriptome were seen between 22qDS patients and healthy controls. Furthermore, a significant inverse correlation was observed between the expression of specific inflammatory cytokines and T cell counts.