Clinical significance of dynamic monitoring of donor-specific HLA antibodies?

  Donor specific antibodies (DSA) are specific antibodies against donor tissue antigens produced in the recipient after organ/tissue transplantation, mainly including HLA antibodies and non-HLA antibodies (e.g. anti-endothelial cell antibodies, anti-wave protein antibodies, anti-MICA antibodies and anti-MICB antibodies).  Currently, the focus of clinical attention is mainly on donor-specific HLA antibodies, and most of the literature reports on DSA refer specifically to HLA antibodies, mainly for the following reasons: ① Human HLA is highly polymorphic and closely related to transplant rejection, so it is also known as transplant antigen; ② HLA antibodies involved in hyperacute rejection have long been the consensus of the international transplant community, and before transplantation The donor-recipient cross-matching test – complement-dependent cytotoxicity test (CDC) has been performed routinely for decades, and new matching methods have been continuously applied in clinical practice, such as anti-human globulin-CDC (AHG-CDC) and flow cytometry cross-matching (FCXM), with the aim of improving the sensitivity of the test and completely excluding the presence of donor-specific HLA antibodies in the recipient; ③ The results of numerous studies have shown that HLA antibody-mediated humoral rejection is closely related to acute and chronic graft injury; ④ The important clinical significance of routine postoperative monitoring of donor-specific HLA antibodies in peripheral blood of patients has been recognized by the international transplant community, and its detection methods have been internationally standardized, such as: enzyme-linked immunosorbent assay (ELISA) and flow-through magnetic bead assay (LABScreen (5) Donor-specific HLA antibodies in peripheral blood can be monitored dynamically for a long time, and specimen collection is less invasive and easily accepted by patients.  In our follow-up observation of anti-donor-specific HLA antibodies in 983 post-transplant recipients, we found that among 325 recipients with impaired renal function and elevated serum creatinine (Scr) levels, donor-specific HLA antibodies were detected in the serum of 104 cases (32%), and in 59 cases (36%) of 162 transplanted kidney puncture biopsy specimens, C4d deposits were found in the peritubular capillary wall (PTC). The donor-specific HLA antibodies were present in the serum of 49 of 76 patients (65%) who had resumed hemodialysis after transplant kidney failure. Moreover, donor-specific HLA antibodies were detected 3-6 months before the impairment of transplanted kidney function, indicating that the appearance of donor-specific HLA antibodies significantly precedes the impairment of transplanted kidney function.  Therefore, dynamic monitoring of donor-specific HLA antibodies in the recipient’s serum after renal transplantation can help to predict and diagnose humoral rejection at an early stage and take timely clinical interventions, such as: (1) adjusting immunosuppression regimen; (2) performing immunosorbent (IA) or plasma exchange (PE) therapy; (3) intravenous immunoglobulin (IVIG) infusion, etc., to effectively control the occurrence of humoral rejection and reduce or delay its The damage to graft function can be reduced or delayed.