Purpose of review: Current immune monitoring practices detect antidonor antibodies and antibody-mediated rejection, and are less suited for the detection of acute cellular rejection (ACR), the predominant form of rejection after transplantation. We review the use of mixed lymphocyte coculture-based assays that measure cellular alloresponses, for measurement of the risk of ACR after liver, intestine, and kidney transplantation.
Recent findings: Flow cytometry enables the rapid measurement of cellular alloresponses using dilution of the intravital dye carboxyfluorescein succinimidyl ester within 72 h or of intracellular CD154 in alloantigen-specific T-cells or B-cells within 16 h. Assay output is personalized by expressing donor-induced alloresponse as a fraction of the third-party alloresponse for each patient. The resulting parameter called the immunoreactivity index indicates increased risk of rejection if donor-response exceeds third-party response. The rejection-risk threshold immunoreactivity index predicts or associates with ACR of liver, kidney, or intestine allografts with sensitivity and specificity of 75% or more. Lifelong assessment is facilitated by using 'surrogate' donor stimulators from normal human individuals in lieu of actual donor cells, without compromising rejection-risk assessment.
Summary: Cellular alloresponses can measure the risk of ACR accurately in the clinic, so that immunosuppression may be managed safely and more effectively in individual patients.