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Abstract: TH-OR106

Serum Proteomic Profiles of Microvascular Inflammation in Donor-Specific Antibody-Negative and C4d-Negative in Kidney Transplantation

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Koh, Hee Byung, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
  • Na, Omi, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
  • Kim, Hyo Jeong, NHIS Ilsan Hospital, Kyungki-do, Korea (the Republic of)
  • Ko, Byounghwi, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
  • Kim, Hyung Woo, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
  • Kang, Minyu, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
  • Kim, Hyun-Jeong, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
  • Lee, Juhan, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
  • Kim, Myoung soo, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
  • Kim, Beom Seok, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
  • Huh, Kyu ha, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
  • Yang, Jaeseok, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
Background

Microvascular inflammation (MVI) has long been considered a hallmark of antibody-mediated rejection (ABMR). However, the 2022 Banff Classification introduced isolated MVI (iMVI; MVI+/DSA-/C4d-) as a distinct phenotype. The biological characteristics and clinical significance of iMVI remain incompletely understood.

Methods

Kidney transplant recipients who underwent allograft biopsy were classified into iMVI, ABMR (MVI+/DSA+/C4d+), and acute tubular injury (ATI; MVI-/DSA-/C4d-). After propensity score matching, 80 patients (30 iMVI, 30 ABMR, and 20 ATI) compromised the main cohort. An independent validation cohort (n=88; 26 iMVI, 26 ABMR, 26 TCMR, 10 ATI) was additionally assembled. Serum proteomic profiling was performed using a proximity extension assay.

Results

iMVI exhibited a distinct proteomic profile enriched for innate and cytotoxic immune activation proteins, including TNFRSF9, PD-L1, IL-15RA, FGF19, CX3CL1, CCL23, SLAMF1, and IL-10RB with enrichment of NK cell differentiation and leukocyte migration pathway. In contrast, ABMR showed higher expression of adaptive and humoral immune mediators, including IL-33, IL-2, TRAIL, and IL-2RB with enrichment of immunoglobulin production and interferon-γ–related adaptive immune pathways. Protein risk scores showed strong discriminative performance in the main cohort (AUC 0.856 for iMVI; 0.879 for ABMR) and retained significant ability in the validation cohort (AUC 0.708 and 0.689). Several iMVI-enriched proteins were significantly associated with increased risk of death-censored graft loss.

Conclusion

iMVI is characterized by dominant innate and cytotoxic immune activation, distinguishing it from conventional ABMR and supporting its recognition as a distinct immunologic entity.

Acknowledgment

This study was supported by a research grant of the Department of Internal Medicine, Yonsei University College of Medicine (2025-2).

Funding

  • Private Foundation Support