October 28, 2024, Immune Tolerance
Tissue or organ rejection may occur when transplants are performed between individuals of different species or between individuals of the same species but different genetic lineages; it is fundamentally an immune response triggered by allogeneic antigens on the cell surface.
Such an allogeneic antigen, which represents individual specificity, is called a transplantation antigen or histocompatibility antigen. Antigens causing strong and rapid rejection are termed major histocompatibility antigens (MHAs), while those causing weaker or slower rejection are termed minor histocompatibility antigens (MiHAs).
In clinical tissue or organ transplantation, MHA matching is typically a prerequisite for successful transplantation.
In humans, MHAs are also known as human leukocyte antigens (HLAs).
HLAs are primarily categorized into two main types:
Class I, which includes HLA-A, HLA-B, and HLA-C, is widely distributed across various tissues and cells.
Class II, which includes HLA-DP, HLA-DQ, and HLA-DR, is present in B cells, macrophages, and activated T cells.
In clinical kidney transplantation, only HLA-A, HLA-B, and HLA-DR are typically tested, totaling six loci, because previous studies have demonstrated that these three molecules are most closely associated with graft rejection.
Recently, international research teams have investigated the impact of HLA-DQ mismatch on kidney allograft rejection.
The study utilized data from dialysis and transplant centers in Australia and New Zealand from 2004 to 2012, employing an adjusted Cox regression model to examine the relationship between HLA-DQ locus mismatch and acute rejection in living or deceased kidney transplant recipients.
Nearly 800 kidney transplant patients underwent an average follow-up of nearly 3 years, with 40.7% of patients receiving no HLA-DQ locus mismatch or a single HLA-DQ locus mismatch from the donor kidney, while 59.3% received donor kidneys with two HLA-DQ locus mismatches. Patients who received kidney transplants with one or two HLA-DQ mismatches were more prone to developing rejection (with late rejection more likely to occur 6 months post-transplantation) and antibody-mediated rejection compared to those who received kidneys without HLA-DQ mismatches.
After adjusting for factors such as age, race, donor kidney type, BMI, the number of HLA-A, B, and DR mismatches, panel reactive antibodies, kidney transplant wait time, ischemia time, induction therapy, and primary immunosuppressive response, follow-up results indicated that kidney transplant recipients with one or two HLA-DQ mismatched donor kidneys had a significantly higher risk of heart failure compared to those without HLA-DQ mismatches. The adjusted hazard ratios for acute or late rejection were 1.54 and 2.85, respectively. HLA-DR loci can effectively modulate the impact of HLA-DQ mismatch and antibody-mediated rejection.
Therefore, the association was more pronounced in recipients of donor kidneys with one or two HLA-DQ mismatches, with an adjusted hazard ratio of 2.50.
The findings confirmed that the increased incidence of acute rejection in this study was attributable to HLA-DQ mismatch, not HLA-A, B, DR mismatches, or primary immunosuppression.
Therefore, in our clinical practice, in addition to focusing on HLA-A, B, and DR locus matching, we should also prioritize HLA-DQ locus matching when assessing the immune-related risks of kidney transplant patients prior to surgery.
Written by | Jina Wang, Edited by | Yichen Jia, Photography | C.M. et al
