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Microvascular inflammation (MVI) is a key histological feature of immune-mediated injury at the capillary interface of renal allografts, characterized by immune cell infiltration into glomerular and peritubular capillaries. Although traditionally associated with antibody-mediated rejection (AMR), many MVI cases lack detectable donor-specific antibodies (DSA), suggesting the involvement of antibody-independent immune mechanisms or alternative triggers, such as viral infections or ischemia-reperfusion injury. The Banff 2022 scheme introduced a subcategory, "MVI, DSA-negative, C4d-negative," within an overarching AMR or MVI category. This subcategory-similar to AMR-was shown to carry a significant risk of graft failure. Its recognition marks a major advancement, offering a robust framework for investigating the pathophysiology of MVI, which may involve a wide array of overlapping triggers. Emerging evidence from transcriptome analyses highlights natural killer cells as possible effectors, regardless of DSA status. Therapies targeting natural killer cells, particularly the anti-CD38 antibody felzartamab, have shown promising reductions in MVI and molecular injury. Notably, the US Food and Drug Administration has approved an MVI-based primary endpoint for a phase 3 trial evaluating this approach, representing a critical step toward the development of new therapeutics. Recognizing MVI as a multifaceted histological phenotype-driven by diverse triggers-may signal a paradigm shift in transplant medicine.
Böhmig et al. (Tue,) studied this question.