Pre-transplant Screening for Non-HLA Antibodies: Who should be Tested?

Area of Science:

• Nephrology
• Transplant Immunology
• Clinical Chemistry

Background:

• Non-HLA antibodies, including angiotensin II type 1 receptor antibodies (AT1R-Ab) and anti-endothelial cell antibodies (AECA), are implicated in kidney allograft injury.
• Rising healthcare expenditures necessitate targeted laboratory testing, prompting investigation into identifying kidney transplant recipients who would benefit from non-HLA antibody screening.

Purpose of the Study:

• To define characteristics of kidney transplant recipients who may benefit from screening for non-HLA antibodies (AT1R-Ab and AECA).
• To correlate pre-transplant non-HLA antibody levels with clinical and biopsy findings indicative of graft dysfunction.

Main Methods:

• Retrospective analysis of kidney transplant recipients from 2011-2016 at Johns Hopkins.
• Measurement of AT1R-Ab via ELISA and AECA via endothelial cell crossmatches.
• Comparison of pre-transplant antibody levels with clinical data and Banff' 2009-2013 graded biopsy results.

Main Results:

• Higher AT1R-Ab levels were observed in patients positive for AECAs.
• Pre-transplant AT1R-Ab positivity was associated with re-transplantation, male gender, FSGS diagnosis, and younger age at transplant.
• Recipients positive for AT1R-Ab showed earlier increases in serum creatinine (within 3 months) and developed abnormal biopsies sooner than AT1R-Ab negative patients.

Conclusions:

• Pre-transplant AT1R-Ab positivity is linked to early post-transplant graft dysfunction and biopsy-proven injury.
• Developing a clinical protocol to identify and preemptively treat at-risk patients with detectable non-HLA antibodies is crucial for the transplant community.
• Targeted screening for non-HLA antibodies may optimize resource utilization and improve kidney transplant outcomes.