Human leukocyte antigen typing and crossmatch: A comprehensive review

Table 1 Summary of the pre-transplant risk assessment of immunological challenge

Donor crossmatch result	Crossmatchmethod	Current or historical	Antibody screening results	Interpretation ofimmunological risk
Positive T and B lymphocyte	CDC (DTT)	C	IgG HLA class I DSA	High risk1
				Hyperacute rejection
				(veto to transplantation)
Positive B lymphocyte	CDC (DTT)	C	IgG HLA class II DSA	High risk1
Positive B lymphocyte	CDC (DTT)	C	Weak IgG HLA class I DSA	Intermediate risk2
Positive T and B lymphocyte	FCXM (CDC neg)	C	IgG HLA class I DSA	Intermediate risk2
Positive B lymphocyte	FCXM (CDC neg)	C	IgG HLA class II DSA	Intermediate risk2
Positive T and B lymphocyte	CDC (DTT)	H	IgG HLA class I DSA	High risk3
Positive B cell	CDC (DTT)	H	IgG HLA class II DSA	High risk3
Positive B lymphocyte	CDC (DTT)	H	Weak IgG HLA class I DSA	Intermediate risk2
Positive T and B lymphocyte	FCXM (CDC neg)	H	IgG HLA class I DSA	Intermediate risk2
Positive B lymphocyte	FCXM (CDC neg)	H	IgG HLA class II DSA	Intermediate risk2
Positive T and B lymphocyte	CDC (neg DTT)	C or H	IgM HLA class I DSA	Standard risk
Positive B lymphocyte	CDC (neg DTT)	C or H	IgM HLA class II DSA	Standard risk
Positive T and B lymphocyte	CDC (neg DTT)	C or H	IgM non-HLA (often autoreactive)	Standard risk
Positive B lymphocyte	CDC (neg DTT)	C or H	IgM non-HLA (often autoreactive)	Standard risk
Negative T and B lymphocyte	FCXM	C or H	IgG HLA class I or II DSA (detected by Luminex SAB alone)	Standard risk
Positive T and/or B lymphocyte	CDC and/or FCXM	C or H	Negative (Luminex Ab detection and/or SAB)	Standard risk (IgM/IgG non-HLA, often showing in vitro autoreactivity)
Positive T; Nnegative B lymphocyte	CDC and/or FCXM	C or H	Positive (Luminex SAB-not donor-specific) or negative	Standard risk (results suggest antibody is not HLA-specific)
Negative T and B lymphocyte	FCXM	C or H	Positive (Luminex SAB) not donor HLA-specific	Standard risk
Negative T and B lymphocyte	CDC and/or FCXM	C or H	Negative (Luminex Ab detection and/or SAB)	Standard risk
Donor crossmatch result	Crossmatch method	Current or historical	Antibody screening results	Interpretation of immunological risk
Positive T and B lymphocyte	CDC (DTT)	C	IgG HLA class I DSA	High risk1
				Hyperacute rejection
				(veto to transplantation)
Positive B lymphocyte	CDC (DTT)	C	IgG HLA class II DSA	High risk1
Positive B lymphocyte	CDC (DTT)	C	Weak IgG HLA class I DSA	Intermediate risk2
Positive T and B lymphocyte	FCXM (CDC neg)	C	IgG HLA class I DSA	Intermediate risk2
Positive B lymphocyte	FCXM (CDC neg)	C	IgG HLA class II DSA	Intermediate risk2
Positive T and B lymphocyte	CDC (DTT)	H	IgG HLA class I DSA	High risk3
Positive B lymphocyte	CDC (DTT)	H	IgG HLA class II DSA	High risk3
Positive B lymphocyte	CDC (DTT)	H	Weak IgG HLA class I DSA	Intermediate risk2
Positive T and B lymphocyte	FCXM (CDC neg)	H	IgG HLA class I DSA	Intermediate risk2
Positive B lymphocyte	FCXM (CDC neg)	H	IgG HLA class II DSA	Intermediate risk2
Positive T and B lymphocyte	CDC (neg DTT)	C or H	IgM HLA class I DSA	Standard risk
Positive B lymphocyte	CDC (neg DTT)	C or H	IgM HLA class II DSA	Standard risk
Positive T and B lymphocyte	CDC (neg DTT)	C or H	IgM non-HLA (often autoreactive)	Standard risk
Positive B lymphocyte	CDC (neg DTT)	C or H	IgM non-HLA (often autoreactive)	Standard risk
Negative T and B lymphocyte	FCXM	C or H	IgG HLA class I or II DSA (detected by Luminex SAB alone)	Standard risk
Positive T and/or B lymphocyte	CDC and/or FCXM	C or H	Negative (Luminex Ab detection and/or SAB)	Standard risk (IgM/IgG non-HLA, often showing in vitro autoreactivity)
Positive T; negative B lymphocyte	CDC and/or FCXM	C or H	Positive (Luminex SAB-not donor-specific) or negative	Standard risk (results suggest antibody is not HLA-specific)
Negative T and B lymphocyte	FCXM	C or H	Positive (Luminex SAB) not donor HLA-specific	Standard risk
Negative T and B lymphocyte	CDC and/or FCXM	C or H	Negative (Luminex Ab detection and/or SAB)	Standard risk

¹High immunological risk: Hyperacute rejection is unlikely (reported only in cases with very high titre HLA-DR antibodies) but donor-specific HLA class II antibodies are increasingly recognised as being associated with refractory humoral rejection and poor transplant prognosis;

²Intermediate immunological risk: Transplantation should be avoided if reasonably possible (i.e., short waiting time, easy to avoid unacceptable mismatches) but may be undertaken with appropriate clinical caution; consideration for enhanced immunosuppression, proactive use of clinical intervention strategies and post-transplant antibody monitoring;

³Risk of anamnestic secondary T and/or B lymphocyte response: Need to consider high risk immunosuppression strategy, the duration, titre and priming source of antibody and repeat mismatches (pregnancy or regraft). Historical positive crossmatches caused by cross-reactive alloantibodies (avoiding the main specificity and priming stimulus) constitute intermediate immunological risk and are less likely to be associated with refractory T or B lymphocyte responses. CDC: Complement dependent cytotoxicity; DTT: Dithiothreitol; HLA: Human leukocyte antigen; DSA: Donor specific antibodies; FCXM: Flow cytometry crossmatch; SAB: Single-antigen beads.