Chronic active T cell-mediated rejection is variably responsive to immunosuppressive therapy

Area of Science:

• Nephrology
• Transplantation Immunology
• Immunosuppression

Background:

• Chronic active T cell-mediated rejection (CA TCMR) is a newly identified kidney transplant rejection type linked to long-term graft loss.
• The relationship between CA TCMR and insufficient immunosuppression, along with treatment efficacy, remains unclear.

Purpose of the Study:

• To investigate the treatability of CA TCMR using immunosuppressive therapy.
• To analyze clinical, histological, and molecular factors influencing outcomes in CA TCMR.

Main Methods:

• Retrospective analysis of 48 isolated CA TCMR cases at a single institution.
• Treatment administered included pulse steroids, anti-thymocyte globulin, or both.
• Response defined as ≥50% estimated glomerular filtration rate (eGFR) recovery.
• Targeted transcriptional profiling was employed.

Main Results:

• Immunosuppressive therapy led to a 20% response rate (≥50% eGFR recovery) within four weeks.
• Treatment response was not associated with concurrent acute T cell-mediated rejection or parenchymal scarring severity.
• A trend suggested better response with moderate versus severe tubulitis.
• Increased allograft mast cells and altered lipid metabolism were linked to treatment resistance.

Conclusions:

• CA TCMR generally has a poor prognosis but is heterogeneous.
• A subset of patients with CA TCMR can experience improved kidney function with immunosuppressive therapy.
• Identifying specific molecular and histological features may predict treatment resistance.