October 25, 2024, Immune Tolerance
If you have some knowledge of transplant surgery, you must recognize that “matching” is a critical component of the procedure. The success of matching directly determines whether the recipient is suitable to receive the corresponding kidney, and the extent of matching is also directly linked to the likelihood of rejection post-transplantation.
So, how does this work? Human leukocyte antigen (HLA) plays a role in the body’s recognition of foreign substances, making the similarity between donor and recipient HLA a direct indicator of the likelihood of subsequent rejection. Based on this, kidney transplant matching requires determining whether the donor and recipient are HLA-matched, typically by testing the donor and recipient for HLA-A, HLA-B, HLA-DR, and similar loci, and comparing their HLA molecular types pairwise; the higher the number of matched pairs, the lower the probability of rejection. Although these matching approaches significantly reduce the risk of rejection, some HLA-matched patients still experience rejection, prompting researchers to explore other histocompatibility antigens, including MICA—the human MHC class I-related gene A—and the polymorphic, unconventional MHC class I molecules it encodes.
MICA is not a new concept. Researchers have recognized for 30 years that these molecules are homologous to MHC class I chains, but have not yet precisely identified their role in post-transplant rejection. MICA is located adjacent to HLA-B and is closely associated with HLA-B types. However, there are instances where MICA undergoes single nucleotide changes, and standard matching experiments cannot assess the degree of MICA matching or its typing. Is it necessary to test MICA independently?
In a paper published in Nature Medicine in May 2022, Carapito and his team suggested that testing for MICA phenotypic matching could reduce the risk of potential graft loss. The study involved 1,356 kidney transplant patients from six centers in France, with a median observation period of 6.3 years and a maximum of 12.9 years. The results revealed that the 5-year graft survival rate for MICA-mismatched patients was 88%, significantly lower than that for MICA-matched patients. Among these, patients with more than two MICA mismatched sites had a higher likelihood of graft loss within 5 years post-surgery. Studies have also identified de novo anti-donor MICA-specific antibodies (de novo anti-MICA DSAs) as a common risk factor for T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR)[1].
These findings underscore the importance of preoperative MICA matching detection; some international transplant centers have started planning to gradually integrate MICA genotyping and DSA testing into the preoperative evaluation of transplant candidates and the postoperative management of transplant recipients [2]. Our center has adopted MICA antibody detection as one of the tools for postoperative evaluation of transplant recipients and will continue to monitor the adoption of new technologies and strategies both domestically and internationally, updating our clinical protocols accordingly.
References:
[1] Carapito, R., et al. The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation. Nature Medicine, 2022. 28(5): 989–998.
[2] Allison, S.J. MICA in kidney transplants. Nature Reviews Nephrology, 2022. 18(5): 273.
This article is an original publication of the “Kidney Transplantation, Zhongshan Hospital, Fudan University” WeChat public account. Reproduction requires authorization from this account and the original author, with proper attribution. To care for your kidneys, begin by following the “Kidney Transplantation, Zhongshan Hospital, Fudan University” WeChat public account. You can also click [Read the Original] to explore A Review of Living Related Donor Kidney Transplant Education Series.
