611 - Iron deficiency and immune dysregulation in children with chronic kidney disease: single cell RNA sequencing analysis of circulating lymphocytes
Sunday, April 27, 2025
8:30am – 10:45am HST
Publication Number: 611.5982
Hannah Federman, Weill Cornell Medicine, New York, NY, United States; Chantalle A. Campbell, Weill Cornell Medicine, New York, NY, United States; Uthra Balaji, Weill Cornell Medicine, ALLEN, TX, United States; Kanza Baqai, Weill Cornell Medicine, New York City, NY, United States; Edwin Patino, Weill Cornell Medicine, New York, NY, United States; Jinghua Gu, Weill Cornell Medicine, New York, NY, United States; M Virginia Pascual, Weill Cornell Medicine, New York, NY, United States; Oleh Akchurin, Weill Cornell Medical College, New York, NY, United States
Postdoctoral Fellow Weill Cornell Medicine New York, New York, United States
Background: Immune dysregulation is a clinically relevant complication of chronic kidney disease (CKD), with poorly understood mechanisms and limited treatments. Iron deficiency (ID), usually functional, is also common in CKD, often requiring iron supplementation. While both ID and iron supplementation affect lymphocyte function in non-CKD settings, their role in immune dysfunction in pediatric CKD remains unclear. Objective: To delineate the relationship between CKD, ID, and the transcriptomic profiles of lymphoid cell populations in children. Design/Methods: Peripheral blood mononuclear cells (PBMCs) were collected from healthy controls (n=6) and pediatric CKD patients (n=12), including 5 ID (defined as TSAT < 20%), and 7 iron-replete patients. Groups were age- and sex-matched. scRNA-seq libraries were prepared using Chromium Single Cell 3’ Reagent Kit V2 (10x Genomics) and sequenced on Illumina HiSeq 2500. Cell clustering was performed with Seurat, and KEGG pathway enrichment analysis with fGSEA. Results: Age (13.3 years for CKD and 14.3 years for control), GFR, hemoglobin, or WBC count were similar between groups. scRNAseq revealed 25 unique lymphoid subclusters, including CD4/CD8 T, B, NK, and plasma cells. Within total lymphocytes, the number of naive CD4 cells was reduced and the number of central memory CD8 cells was increased in CKD patients compared to controls. The CD56-dim subpopulation of NK cells was reduced in the CKD group. Proliferating NK, gd-T, and CD8 memory T cells were among the clusters with the highest number of differentially expressed genes between both CKD and control groups and between iron-deficient and iron-sufficient CKD sub-groups. Genes involved in antigen-receptor binding, like galectin 1 (LGALS1), were induced in CD8 T cells in ID-CKD. Increase of HLA-DRB1 in NK cells and KLF-5 in B cells in ID-CKD was also noted, alongside genes driving Fc-gamma R-mediated phagocytosis and chemokine-signaling in B and T cells in ID-CKD. This pathway upregulation was found in Th1 (but not in Th2) cells, suggesting an ID-driven polarized immune response. B-cell receptor signaling pathway was significantly positively enriched for naïve B cells and plasma cells in the iron-deficient group compared to the healthy controls.
Conclusion(s): This study is the first, to our knowledge, to define lymphoid immunity in pediatric CKD using single-cell transcriptomics. While iron supplementation is perceived to be pro-inflammatory in CKD, our data suggest that iron-deficient pediatric CKD patients exhibit immune pathway activation in lymphocytes, potentially driving systemic inflammation.
