Impact of donor-specific antibodies on the outcomes of kidney graft: Pathophysiology, clinical, therapy

Table 1 Technological advantages and limitations of luminex human leukocyte antigens single antigen bead

Technological advantages	Technological limitations
Qualitative: enables precise identification of all antibody specificities in complex sera (DSA)	Some positive results can be caused by antibodies to denatured HLA
Comprehensive: distinguishes antibodies to all common alleles for HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DRB3/4/5, HLA-DQA1, HLA-DQB1, HLA-DPA1, HLA-DPB1	Occasional high background binding requiring repeat testing and absorption protocols
Semiquantitative: enables determination of antibody levels (high, intermediate, and low)	Variable HLA protein density on beads. Blocking factors may cause false-negative or misleading low assessment of antibody levels (prozone?); IgM and C1 can block IgG binding
Sensitive: enables detection of weak antibody testing
Rapid: enables real-time antibody monitoring for DSA. Pre- transplantation and post-transplantation antibody monitoring (assist diagnosis of ABMR). Virtual XM	Lot-to-lot variation requiring validation. Vendor-specific variation
Enables detection of non-HLA-specific antibodies (e.g., MICA)
Detection and differentiation between immunoglobulin class and isotype (e.g., complement fixing and non-complement fixing C4d and C1q	Reagents not standardized

ABMR: Antibody mediated rejection; DSA: Donor specific HLA antibodies; HLA: Human leukocyte antigens; MICA: Major histocompatibility complex class I-related chain A; SAB: Single-antigen beads; XM: Cross-match.

Table 2 Anti-antibodies main drugs to date in use and mechanism of action

Steps	Cells or mechanisms involved	Drugs	Mechanism of action
Exposure to antigen	B Cells	Rituximab ivig	Binds CD20 on B cells and mediates cell lysis Multiple B cell apoptosis, decrease in B-cell proliferation
Secretion of alloantibodies	Plasma cells; antibodies	Bortezomib	Decrease donor-specific alloantibody production Mechanical removal of alloantibodies
		Plasma- exchange ivig	Multiple B cell apoptosis, decrease in B-cell proliferation
Binding of antibodies to the graft	Complement activation	Eculizumab	Blocks cleavage of terminal complement C5 and halts the process of complement-mediated cell destruction