Crossmatch

Crossmatch is a laboratory test used in transplantation to determine whether a recipient has preformed antibodies against a potential donor’s human leukocyte antigens (HLA). Its purpose is to assess the risk of antibody-mediated rejection, particularly hyperacute rejection, by identifying donor-specific antibodies in the recipient before proceeding with a transplant. Crossmatching is commonly performed in solid organ transplantation and is integral to donor–recipient risk assessment, sometimes complemented by virtual crossmatching that uses detailed HLA typing and antibody screening results.

The test involves exposing donor cells, typically lymphocytes, to the recipient’s serum and detecting whether antibodies in the serum bind to the donor cells. There are two main forms: cell-based crossmatches and antibody testing-based approaches. In the conventional cell-based crossmatch, the binding of recipient antibodies to donor T cells (primarily HLA class I) and B cells (HLA class I and II) is assessed. Methods include complement-dependent cytotoxicity (CDC) crossmatch, where binding triggers cell lysis, and flow cytometry crossmatch (FCXM), which detects antibody binding with fluorescent labeling and is more sensitive. A negative crossmatch suggests a reduced risk of immediate antibody-mediated rejection, while a positive crossmatch indicates the presence of donor-specific antibodies and generally contraindicates using that donor unless desensitization or alternative strategies are employed.

Results interpretation guides management. Positive crossmatches may lead to donor unavailability or prompt desensitization approaches, such as plasmapheresis, intravenous immunoglobulin, or targeted biologic therapies. Limitations include false positives from non-HLA antibodies and false negatives from low antibody levels, underscoring the need for expert interpretation.