Circulating follicular T helper cells and humoral reactivity in rheumatic heart disease
Zongtao Liu1, Yixuan Wang1, Fei Li1
1From the Cardiovascular Surgery, Wuhan Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
Insights
Circulating T follicular helper cells (cTfh), particularly PD-1+ and cTfh17 subtypes, are elevated in rheumatic heart disease (RHD). This immune cell activation correlates with increased plasmablasts and IL-21, highlighting their role in RHD pathogenesis.
Area of Science:
- Immunology
- Cardiovascular Disease Research
Background:
- Rheumatic heart disease (RHD) is a significant cause of acquired valvular heart disease.
- The role of specific immune cell subsets, such as circulating T follicular helper cells (cTfh), in RHD pathogenesis is not fully understood.
Purpose of the Study:
- To profile cTfh cells and their impact on B cells in patients with RHD.
- To investigate the correlation between cTfh subpopulations, B cell subsets, and IL-21 levels in RHD.
Main Methods:
- Flow cytometry was used to quantify cTfh subpopulations (based on CD4, CXCR5, CXCR3, CCR6, Foxp3, Ki67, PD-1) and B cell subsets (CD19+) in healthy controls (n=30) and RHD patients (n=30).
- IL-21 concentrations were measured in plasma and mitral valve tissue using cytometric bead array, immunofluorescence, and western blotting.
Main Results:
- RHD patients showed significantly increased percentages of PD-1+ cTfh cells, plasmablasts, and plasma B cells, along with higher cTfh17/cTfh ratios compared to healthy controls.
- Memory B cell populations were diminished in RHD patients.
- PD-1+ cTfh cell percentages positively correlated with plasmablasts and IL-21 levels, while negatively correlating with switched memory B cells.
Conclusions:
- Activated PD-1+ cTfh and cTfh17 cells are closely linked to plasmablast differentiation and elevated IL-21 production in RHD.
- These findings underscore the critical involvement of cTfh cells and humoral immune responses in the immune pathogenesis of RHD.
Aims:
This study aimed to profile circulating T follicular helper cells (cTfh) and their effect on B cells in rheumatic heart disease (RHD).
Materials And Methods:
Participants were divided into healthy control (HC, n = 30) and RHD (n = 30) groups. Percentages of cTfh subpopulations, based on CD4, CXCR5, CXCR3, CCR6, Foxp3, Ki67, and PD-1 cell markers, and of CD19+ B cell subgroups were measured by flow cytometry and compared between the groups. Also, IL-21 concentration in plasma and mitral valve were quantitated by cytometric bead array, immunofluorescence, and western blotting.
Key Findings:
The PD-1+ cTfh, B cells (naive B cells, plasmablasts, and plasma B cells) proportion and cTfh17/cTfh ratios in RHD group were significantly increased, compared to HC (p < 0.01 in all cases), while different types of memory B cells were diminished (p < 0.001). In RHD patients, percentages of PD-1+ cTfh and switched memory B cells were negatively correlated (r = -0.565, p = 0.009); meanwhile, percentages of plasmablasts and PD-1+ cTfh cells were positively correlated (r = 0.594, p = 0.005). Additionally, IL-21 levels in plasma and mitral valve of RHD group were higher than those in HC. Also, IL-21 levels correlated with PD-1+ cTfh(r = 0.557, p = 0.010), cTfh17 (r = 0.567, p = 0.009), and plasmablast (r = -0.5957, p = 0.005) cell proportions, and (cTh2 + cTh17)/cTfh1 ratio (r = -0.547, p = 0.013).
Significance:
The activation of PD-1+ cTfh and cTfh17 subtype was highly correlated with plasmablast maturation and IL-21 production in rheumatic heart disease. Thus indicating the prominent role of cTfh and humoral reactivity in the immune pathogenesis of RHD.
Related Concept Videos
01:22Rheumatic Heart Disease II: Clinical Manifestations and Diagnostic Studies
01:23Rheumatic Heart Disease I: Introduction
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:20Rheumatic Heart Disease IV: Nursing Management
01:36Humoral Immune Responses
01:21Rheumatic Heart Disease III: Medical Management