Reported by South Korea Daily Report | Research from National Health Insurance Service Ilsan Hospital, Goyang, South Korea

Researchers at National Health Insurance Service Ilsan Hospital have published new findings on microvascular inflammation (MVI) in kidney transplant recipients, offering insight into a phenotype that has only recently been formally classified.

Background

MVI has long been considered a hallmark of antibody-mediated rejection (AMR). However, the 2022 Banff classification introduced isolated MVI (iMVI; MVI+/donor-specific antibody [DSA]-/C4d-) as a distinct phenotype. The biological characteristics and clinical significance of iMVI have remained incompletely understood.

Study Design

Kidney transplant recipients who underwent allograft biopsy between 2013 and 2024 were classified into three groups: iMVI, AMR (MVI+/DSA+/C4d+), and acute tubular injury (ATI; MVI-/DSA-/C4d-). After propensity score matching, 80 patients — 30 iMVI, 30 AMR, and 20 ATI — comprised the main cohort. An independent validation cohort of 88 patients (26 iMVI, 26 AMR, 26 T-cell-mediated rejection, and 10 ATI) was additionally assembled. Serum proteomic profiling was performed using a proximity extension assay.

Key Findings

iMVI exhibited a distinct proteomic profile enriched for innate and cytotoxic immune activation proteins, including:

  • Tumor necrosis factor receptor superfamily member 9
  • Programmed death-ligand 1
  • Interleukin-15 receptor subunit alpha
  • Fibroblast growth factor 19
  • C-X3-C motif chemokine ligand 1
  • C-C motif chemokine ligand 23
  • Signaling lymphocytic activation molecule family member 1
  • Interleukin-10 receptor subunit beta

These proteins were associated with enrichment of natural killer cell differentiation and leukocyte migration pathways.

In contrast, AMR showed higher expression of adaptive and humoral immune mediators — including interleukin-33, interleukin-2, TNF-related apoptosis-inducing ligand, and interleukin-2 receptor subunit beta — with enrichment of immunoglobulin production and interferon-γ–related adaptive immune pathways.

Protein risk scores demonstrated strong discriminative performance in the main cohort (area under the curve: 0.856 for iMVI; 0.879 for AMR) and retained significant ability in the validation cohort (AUC: 0.708 and 0.689, respectively). Several iMVI-enriched proteins were significantly associated with increased risk of death-censored graft loss.

Conclusion

The researchers concluded that iMVI is characterized by dominant innate and cytotoxic immune activation that is distinct from AMR and is associated with adverse graft outcomes, supporting its recognition as a clinically meaningful phenotype beyond conventional AMR.

Publication Details

This peer-reviewed research was published as Serum Proteomic Profiles of Microvascular Inflammation in Donor-specific Antibody-negative and C4d-negative in Kidney Transplantation in the journal Transplantation (Lippincott Williams & Wilkins). The DOI is https://doi.org/10.1097/tp.0000000000005839.

The lead contact for this research is Hyo Jeong Kim, Dept. of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, South Korea. Additional authors include Hee Byung Koh, Hyung Woo Kim, Byounghwi Ko, Minyu Kang, Hyun Jeong Kim, Juhan Lee, Myung Soo Kim, Beom Seok Kim, Kyu Ha Huh, and Jaeseok Yang.