Introduction: CD47 emerges as a guardian in renal immunomodulation, shielding against unwanted phagocytosis by macrophages. Its strategic presence across intrinsic renal cells and immune counterparts orchestrates a symphony of functions crucial for renal immune homeostasis. Responsive to various cues, including inflammation and immune triggers, CD47 dynamically adjusts, subtly shaping the delicate balance between immune activation and tolerance. However, dysregulated CD47 expression unveils a sinister side, potentially fueling immune-mediated assaults and triggering allograft rejection (AR). We aim to examine CD47 expression within the kidney to understand the graft's immune milieu and unveil a roadmap to foresee the lurking risks of rejection.
Methods: This study delved into the intricate dynamics of CD47 expression within the renal microenvironment of 126 patients. Focused on recipients with antibody-mediated rejection (ABMR) and those with mixed rejection comprising both T-cell-mediated AR and ABMR, the study explored the correlation between CD47 expression and various parameters across distinct renal compartments, including peritubular capillaries (PTCs) endothelial cells (ECs), interstitial cells (ICs), tubules, and glomeruli. The prognostic implications of CD47 were also studied by evaluating its relation with the development of interstitial fibrosis (IF), transplant glomerulopathy (TG), and transplant arteriosclerosis (TA) in subsequent follow-up biopsies.
Results: CD47 expression in ECs and ICs exhibited a significant association with the type of AR (p<.05). Furthermore, the severity of tubulitis, PTC itis, glomerulitis, interstitial inflammation, macrophage, and HLA-DR positive cells demonstrated a negative correlation with the degree of CD47 expression in tubular, mesangial, endothelial, and interstitial cells (p<.01). Additionally, the extent of CD47 expression in ECs, inflammatory cells, mesangial cells, and tubules was negatively linked to the presence of vascular rejection and proteinuria as well as the PTC destruction and the grade of C4d expression in PTCs (p<.001). Notably, a reduction in CD47 expression in ECs, tubules, interstitium, and mesangium was associated with an increased risk of developing IF TG, TA, and proteinuria (p<.01). Except for mesangial CD47 expression; all other renal CD47 findings significantly associated with the risk and average time of graft loss (p<.001).
Conclusion: The strategic presence of CD47 within intrinsic renal cells and infiltrating immune counterparts orchestrates a symphony of functions vital for maintaining renal immune homeostasis. The downregulation of renal CD47 expression reveals a darker aspect, potentially fueling immune-mediated assaults and precipitating AR. Exploring the intricate CD47 expression patterns within renal biopsies not only provides insights into the graft's immune milieu but also unveils a roadmap to anticipate the lurking risks of rejection, graft injury, and graft loss.