A T cell crossmatch is negative by AHG-CDC but positive by flow crossmatch. What is the most likely explanation?

In the scenario presented, the negative T cell crossmatch by AHG-CDC (antihuman globulin-complement dependent cytotoxicity) alongside a positive flow crossmatch suggests a specific interaction characteristic of antibody detection.

A negative result with AHG-CDC indicates that the complement-dependent cytotoxicity is not activated, which typically occurs in the presence of IgM antibodies or low titer IgG antibodies that do not effectively activate the complement system. Flow cytometry is more sensitive and can detect lower levels of antibodies that might not result in cell lysis by traditional cytotoxicity methods.

Therefore, the most likely explanation for the negative AHG-CDC result, coupled with a positive flow crossmatch, is that the antibodies present are at a very low titer. These low-titer antibodies may be sufficient to bind to the target cells detected by flow cytometry but insufficient to trigger the full complement activation necessary to cause a cytotoxic effect in an AHG-CDC assay. This highlights the sensitivity discrepancy between the two methods, emphasizing that flow cytometry can detect lower levels of antibodies than those required for the complement-mediated lysis seen in traditional cytotoxicity tests.