Abstract: FR-PO1074
Immune Cell Profiles in Children with Essential Hypertension (EH)
Session Information
- Pediatric Hypertension, AKI, Urologic Disorders
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1700 Pediatric Nephrology
Authors
- Trachtman, Howard, NYU Langone Health, New York, New York, United States
- Pehrson, Laura Jane, New York University School of Medicine, New York, New York, United States
- Malaga-Dieguez, Laura, New York University School of Medicine, New York, New York, United States
- Alexandre, Jason M., NYU Langone Health, New York, New York, United States
- Chattopadhyay, Pratip K., NYU Langone Health, New York, New York, United States
Background
There is growing evidence that sodium is stored in a non-osmotic form in the interstitial compartment of skin and muscle. In these sites, sodium may contribute to the development of EH by altering the immune system. These effects may be reflected in peripheral blood (PB). We tested PB of children with EH to examine the diversity of immunophenotypes, and to test whether disease treatment changed circulating cells. We deployed high parameter flow cytometry, which allowed detailed characterization of T-cell subsets.
Methods
Eight pediatric patients with EH were enrolled. PB was collected at baseline for all patients, and after 4 and 16 weeks of anti-hypertensive treatment for 3 patients. We designed a 24-parameter flow cytometry panel to enumerate various T-cell subsets, including naïve, memory, dividing, exhausted, regulatory, and suppressive cells. We analyzed data using t-sne, a dimension reduction algorithm that provides a broad overview of the landscape of T-cell immunophenotypes, and applied bivariate difference gating to identify the cell populations uniquely altered with treatment.
Results
At baseline, 7 of 8 patients showed the expected diversity in T-cells subsets. There were dominant populations that differed by patient, suggesting heterogeneity that might be linked to clinical outcome. The 8th patient had a striking polarization in T-cell phenotype at baseline, with two major subpopulations and very few other cells. Her “skewed” T-cell landscape resolved with treatment, and we could precisely identify the cells lost. Cells were uniformly CD4+CD45RA+CD127+CD25-CD38+CCR4-Ki67-LAG3+CTLA4-CD39-IDO-HELIOS-FoxP3-CXCR3-GITR+. This phenotype represents a class of naïve, non-classical regulatory (i.e., suppressive) T-cells. Subsets also expressed other suppressive markers like LAP, GARP, and CD73. Interestingly, the other two patients also showed loss of cells expressing LAG3, CD73, LAP, and/or GARP with treatment.
Conclusion
Children with EH have heterogeneous regulatory T-cell subsets. Successful control of blood pressure with anti-hypertensive drugs re-shapes the T-cell landscape in PB, reducing the number of suppressive T-cells. Our approach – to precisely identify specific cell types altered with disease – is well-suited to identifying biomarkers, and can provide detailed mechanistic information that informs treatment approaches.
Funding
- NIDDK Support