Dysregulation of Immune Cell Subpopulations in Atypical Hemolytic Uremic Syndrome
Abstract
:1. Introduction
2. Results
2.1. The Demography of Studied Cases
2.2. The Immunological Landscape of Immune Cells from aHUS, aHUS Family, and Healthy
2.3. Cell Populations in PBMCs
2.3.1. Comparing aHUS Patients, aHUS Family, and Healthy Controls
2.3.2. Comparing Stable and Unstable aHUS Patients, aHUS Family, and Healthy Controls
2.3.3. Comparing Different Treatment in aHUS Patients, aHUS Family, and Healthy Controls
2.4. Cell Subclusters in PBMCs
2.4.1. Comparing aHUS Patients, aHUS Family, and Healthy Controls
2.4.2. Comparing Stable and Unstable aHUS Patients, aHUS Family, and Healthy Controls
2.5. Trajectory Analysis for B-Cell, T-Cell, and Monocyte
2.5.1. Comparing aHUS Patients, aHUS Family, and Healthy Control
2.5.2. Comparing Stable and Unstable aHUS Patients, aHUS Family, and Healthy Controls
2.6. Immune Cell Interactions in Blood Samples from aHUS, aHUS Family, and Healthy Control
3. Discussion
4. Materials and Methods
4.1. Patient Recruitment
4.2. Single Cell RNA-Seq and Data Analysis
4.3. Single Cell RNA-Seq Data Integration and Clustering
4.4. Cell Type Annotations
4.5. Clustering Analysis
4.6. Pseudotime Estimation
4.7. Cell–Cell Communication Analysis
4.8. Statistical Analysis
4.9. Ethics Approval and Consent to Participate
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
aHUS | Atypical hemolytic uremic syndrome |
TMA | Thrombotic microangiopathy |
CH50 | 50% hemolytic complement activity |
PBMCs | Peripheral blood mononuclear cells |
scRNA-seq | Single-cell RNA sequencing |
PCA | Principal component analysis |
rPCA | Robust principal component analysis |
UMAP | Uniform manifold approximation and projection |
NK | Natural killer |
Mono | Monocytes |
Ma | Macrophages |
DC | Dendritic cells |
STRING | Search Tool for the Retrieval of Interacting Genes/Proteins |
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Case | Age | Gender | TMA Involvement Organ | Treatment | Disease Activity |
---|---|---|---|---|---|
a1 | 39 | M | Kidney, brain, lung, heart | PE | Stable |
a3/a5 | 81 | M | Kidney, heart | a3 before 1st PE a5 after PE | Unstable |
a4 | 66 | M | Kidney, brain, heart | PE + anti C5 | Stable |
a7 | 36 | F | Kidney, heart, pancreas, eye | PE + anti C5 | Stable |
a8 | 33 | F | Kidney, brain, lung, heart | PE | Unstable |
a9 | 62 | F | Kidney, brain, heart | PE + anti C5 | Unstable |
a10 | 39 | M | Kidney, brain, lung, heart, eye | PE + anti C5 | Stable |
a11 | 30 | F | Kidney, brain, lung, heart, eye, bowel | PE + anti C5 | Stable |
a12 | 42 | F | Kidney, brain, lung, heart, pancreas, liver, eye, skin | PE + anti C5 | Stable |
a13 | 53 | M | Kidney, brain, heart | PE + anti C5 | Stable |
a14 | 70 | M | Kidney, brain, heart | PE | Unstable |
a16 | 62 | F | Kidney, heart | PE | Stable |
a17 | 49 | F | Kidney, brain, lung, heart, pancreas, liver, eye | PE + anti C5 | Stable |
Significantly Increased Immune Cell Subclusters in aHUS Patients Compared to Healthy Controls with Correlated Gene Expression Increasing | |||
Cell Subclusters | p value | Higher expression levels of gene | |
Classical monocyte subclusters 6 | p < 0.01 | RPS27 | |
Classical monocyte subclusters 7 | p < 0.05 | IFI27 | |
Central memory CD8 T-cells subcluster 3 | p < 0.05 | CXCR4 | |
Non-Vd2 gd T-cells subcluster 4 | p < 0.05 | SYNE2 | |
Th1 cells subcluster 3 | p < 0.05 | MT-CYB | |
Th17 cells subcluster 4 | p < 0.05 | MT-ATP6 | |
Significantly Increased Immune Cell Subclusters in Healthy Controls Compared to aHUS Patients with Correlated Gene Expression Increasing | |||
Cell Subclusters | p value | Higher expression levels of gene | |
Central memory CD8 T-cells subcluster 1 | p < 0.05 | EIF3E | |
Th1 cells subcluster 0 | p < 0.05 | RPS27 | |
Non classical monocytes subcluster 5 | p < 0.01 | LYPD2 | |
Terminal effector CD4 T-cells subcluster 3 | p < 0.01 | KLRD1 | |
Th17 cells subcluster 3 | p < 0.05 | ACTG1, CD52 and LGALS1 |
Significantly Increased Immune Cell Subclusters in Unstable aHUS Patients Compared to Stable aHUS Patients with Correlated Gene Expression Increasing | |||
---|---|---|---|
Cell Subclusters | p value | Higher expression levels of gene | |
Classical monocyte subclusters 4 | p < 0.05 | NEAT1, MT-ATP6 and MT-CYB | |
Central memory CD8-T cells subcluster 2 | p < 0.05 | VIM | |
Non-Vd2 gd T-cells subcluster 1 | p < 0.05 | ACTG1 | |
Terminal effector CD8—cells subcluster 3 | p < 0.05 | RPL13 | |
Terminal effector CD8 T-cells subcluster 5 | p < 0.01 | KLRB1 | |
Significantly Increased Immune Cell Subclusters in stable aHUS Patients Compared to unstable aHUS Patients with Correlated Gene Expression Increasing | |||
Cell Subclusters | p value | Higher expression levels of gene | |
Central memory CD8 T-cells subcluster 1 | p < 0.05 | RPL23 | |
Non-Vd2 gd T-cell subcluster 0 | p < 0.05 | GZMH | |
Th1 cells subcluster 0 | p < 0.05 | RPS27, RPS4X |
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Chen, I.-R.; Huang, C.-C.; Tu, S.-J.; Wang, G.-J.; Lai, P.-C.; Lee, Y.-T.; Yen, J.-C.; Chang, Y.-S.; Chang, J.-G. Dysregulation of Immune Cell Subpopulations in Atypical Hemolytic Uremic Syndrome. Int. J. Mol. Sci. 2023, 24, 10007. https://doi.org/10.3390/ijms241210007
Chen I-R, Huang C-C, Tu S-J, Wang G-J, Lai P-C, Lee Y-T, Yen J-C, Chang Y-S, Chang J-G. Dysregulation of Immune Cell Subpopulations in Atypical Hemolytic Uremic Syndrome. International Journal of Molecular Sciences. 2023; 24(12):10007. https://doi.org/10.3390/ijms241210007
Chicago/Turabian StyleChen, I-Ru, Chiu-Ching Huang, Siang-Jyun Tu, Guei-Jane Wang, Ping-Chin Lai, Ya-Ting Lee, Ju-Chen Yen, Ya-Sian Chang, and Jan-Gowth Chang. 2023. "Dysregulation of Immune Cell Subpopulations in Atypical Hemolytic Uremic Syndrome" International Journal of Molecular Sciences 24, no. 12: 10007. https://doi.org/10.3390/ijms241210007