CHAPTER 41: Immune Risk Profiling

INTRODUCTION

Uncontrolled donor-specific alloimmune response mediates renal allograft injury that leads to graft loss. Immune risk profiling of kidney transplant recipients seeks to identify immunologically appropriate donor–recipient pairs that will result in immunologically successful transplantation.

PURPOSE

• Prevention of hyperacute rejection

• Minimization of acute cellular rejection (ACR) and acute antibody mediated rejection (AAMR)

• Provision of a guide to immunosuppressive strategies

• Minimization of de novo human leukocyte antigen (HLA) donor-specific antibody (DSA)–associated chronic AMR

APPROACH

A standardized four-step approach:

• Establish donor–recipient ABO blood group compatibility and the degree of HLA match/immunogenic mismatch

• Establish donor–recipient HLA compatibility and the degree of HLA match/immunogenic mismatch

• Determine the need for enrollment in kidney-paired donation (KPD) program or desensitization for immunologically incompatible cases

• Stratify immunological risks

DONOR–RECIPIENT ABO BLOOD GROUP COMPATIBILITY

The goal of establishing donor–recipient ABO compatibility is to prevent hyperacute rejection and acute AMR.

• ABO blood group antigen system is the first established histocompatibility barrier to kidney transplantation

• ABO antigens are expressed on vascular endothelium

• “Natural” antibodies of immunoglobulin M (IgM) and G (IgG) classes (isohemagglutinins) are developed early in life (usually beyond 6 months of age) against A, B, and AB antigens that are not expressed on their own erythrocytes (e.g., O blood group recipient forms isohemagglutinins against A and B blood group antigens)

• In case of ABO-incompatible kidney transplantation, the isohemagglutinins bind to their targeted antigens on vascular endothelium, and they trigger complement-dependent antibody-mediated injury (hyperacute rejection or accelerated acute AMR)

• Both donor and recipient are typed for ABO blood group antigens

• In conventional kidney transplantation, the following kidney allocation rules are applied:

  • Donor–recipient ABO identity or compatibility is applied in living donor (LD) transplantation

  • Donor–recipient ABO identity is applied in deceased donor (DD) transplantation. Identity, not compatibility, is applied in DD transplantation to account for the disproportionate distribution of certain blood group recipients on DD list

DONOR–RECIPIENT HLA COMPATIBILITY

Similar to ABO compatibility, the goal of establishing donor–recipient HLA compatibility is to prevent hyperacute rejection and acute AMR.

• HLA system is the second established histocompatibility barrier (positive donor-specific HLA crossmatch) to kidney transplantation

• HLA antigens class I (A, B, C) and class II (DR, DQ, DP) are expressed on vascular endothelium

• “Acquired” antibodies of IgG class are developed against disparate HLA antigens through blood transfusions, multiple pregnancies, and previous organ transplantation

• In case of HLA-incompatible kidney transplantation, the preformed HLA antibodies bind to their targeted antigens (class I and/or II HLA antigens) on vascular endothelium, and they trigger complement-dependent antibody-mediated injury (hyperacute rejection or accelerated acute AMR)

• The laboratory methodology required for establishing donor–recipient HLA compatibility is:

  • Donor and recipient molecular deoxyribonucleic acid (DNA)–based HLA typing

  • Recipient HLA single antigen (SA) antibody detection by solid-phase immunoassay (SPI). Virtual crossmatch is established by ...