Crossmatching with B and T cells and flow cytometry

Area of Science:

• Nephrology
• Transplant Immunology
• Immunogenetics

Background:

• Hyperacute rejection is a severe complication following organ transplantation.
• The presence of preformed antibodies (cytotoxins) in recipients is a known risk factor for rejection.
• Understanding the impact of different crossmatch variations on transplant outcomes is crucial for improving graft survival.

Purpose of the Study:

• To evaluate the incidence of hyperacute rejection in first cadaver donor grafts and regrafts.
• To assess the correlation between various microcytotoxicity crossmatch test results and kidney transplant outcomes.
• To identify specific antibody types and crossmatch profiles associated with reduced graft survival.

Main Methods:

• Analysis of hyperacute rejection rates in a large cohort of first cadaver donor grafts (19,415) and regrafts (4,326).
• Crossmatching of 923 first cadaver donor transplants and 238 multiple transplants using six variations of microcytotoxicity tests.
• Statistical comparison of graft survival rates based on crossmatch results (standard, long incubation, B/T lymphocytes at different temperatures).

Main Results:

• Hyperacute rejection occurred in 0.6% of first grafts and 1.9% of regrafts.
• Positive crossmatches, specifically long positive and T warm positive, were associated with significantly lower graft survival in first transplants.
• Short positive and T warm positive crossmatches also indicated lower graft survival in regrafted patients.
• Preformed T warm cytotoxins correlated with lower graft survival in first grafts, while B warm cytotoxins were linked to lower survival in regrafts.
• Eight patients with T warm positive crossmatches achieved successful transplantation after IgM antibody removal.

Conclusions:

• Specific crossmatch results, such as T warm positive, are significant predictors of reduced kidney graft survival.
• The type of preformed antibody (T warm vs. B warm) influences graft survival differently in first transplants versus regrafts.
• Further investigation into antibody characteristics, like IgM antibodies removable by 2-ME treatment, may offer strategies for successful transplantation in crossmatch-positive patients.