Defining Antibody Mediated Rejection

201 Pages·2013·41.49 MB·English

Defining Antibody Mediated
Rejection:
A UCLA Cross-Disciplinary Workshop to improve
diagnosis and treatment of Acute and Chronic AMR
Friday, Oct. 25, 2013 / Tamkin Auditorium, B-130
Ronald Reagan UCLA Medical Center

Defining Donor Specific Antibodies
Jennifer Q. Zhang
UCLA Immunogenetics Center
Department of Pathology
UCLA School of Medicine
Immunologic Barriers to Transplantation
HLA antigens
MHC class I (HLA‐A, B, C)
MHC class II (HLA‐DR, DP, DQ)
ABO blood group antigens
Non‐HLA antigens
Collagen Type IV, and VI
Vimentin,  Myosin
MHC Class I related chain A (MICA)
Angiotensin II type I receptor (AT1R)
Humoral Alloreactivity to HLA
• Pregnancy
• Blood Transfusion (Artificial devices)
• Transplantation (Use of tissue allografts for
vascular reconstruction in congenital heart
surgery)
• Bacterial / Viral Infection
THE CLINICAL PROBLEM 
Sensitization rates:
• 30% of patients awaiting for renal/liver and small bowel
Transplant
• 15-20% of patients awaiting for heart/lung transplant
Consequences of Preformed anti-donor HLA
Antibodies
• Hyperacute rejection, Accelerated acute rejection
• Delayed graft function
• Chronic rejection
• Prolonged waiting times
• No transplantation
Goals of the Antibody Detection
 Sensitivity
Is there an HLA antibody present? 
What is the antibody titer?
 Specificity
Is the antibody clinical relevant? 
Precise detection of ALL HLA specificities
What are the isotypes – IgG or IgM
Are they able to fix complement (IgG vs IgG )?
1,3 2, 4
Are they donor‐specific HLA antibodies?
Antibody Detection Methods
Methods HLA Antigen
CDC
Native
Crossmatch
Cell Based 
Flow 
Native
Crossmatch
Phenotype
PRA
Affinity Purified
Solid Phase
SAB Recombinant
C1q‐SAB Recombinant
Hyperacute Rejection (CDC+)
Chronic Rejection
Accelerated Rejection
Accommodation?
(FLOW+/CDC-)

f
o y
t d T/B Flow Crossmatch
n o
u b
o i Solid-phase assays
t
m
n Cell based assays
A A
CDC Luminex® Luminex
Flow PRA Flow SAB
Sensitivity & Specificity ↑
Luminex Single Antigen vs C1q Test
Anti-HLA antibodies Anti-HLA antibodies
Non-complement fixing Complement fixing
C1Q
SAB
SAB
Detect complement fixing
Detect all IgG antibodies IgG1/IgG3 and IgM
antibodies
Management of Unacceptable Antigens
• Cytotoxic antibodies
• Single Antigen Test
– Renal/Pancreas: Luminex SAB > 8,000 MFI
(Antibodies with predicted flow xm > 200)
– Pediatric Renal: 1,000 MFI
– Heart/Lung/Small Bowel: Luminex SAB >5,000 MFI
– C1q+ for Heart/Lung
– Liver?
• Luminex PRA > 2,000 MFI
• All specificities for regraft candidates
Update UNET when tests are reviewed