Documenti di Didattica
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Author
# Bxs/Pts
Indication
C4d+ (% Pt)
Feucht 1993
93/93
Renal dysfunction
Lederer 2001
310/218
Renal dysfunction
Regele 2001
102/61
Renal dysfunction
51%
Bohmig 2002
113/58
Renal dysfunction
28%
Nickeleit 2002
398/265
Renal dysfunction
35%
Herzenberg 2002
126/93
Rejection
37%
Mauiyyedi 2002
67/67
Renal dysfunction
30%
213/213
Renal dysfunction
34%
Regele 2002
46%
46% primary
72% regraft
Sund 2003
37/37
Protocol
30%
Koo 2004
96/48
Protocol
13%
111 (74%)
39 (26%)
African-American
White
32 39
Hispanic/Latino
Asian
3 8
Other
<1
63 36
2
16
African-American
White
Hispanic/Latino
Asian
Other
52
45
1
2
0
USA average(%)
30
49
14
6
2
EUH
USA
51%
32%
18%
0%
64%
22%
11%
4%
% Graft Survival
99
90
94
UNOS
97
Emory N = >500
90
93
N = 20791
80
81
70
60
50
3 mos
UNOS/SRTR 2003
Years
Enhanced Cytotoxicity
Flow Cytometry
Anti-HLA Antibody
Ly
Ly
Ly
Anti-Human Globulin
Fluorescenated
Anti-Human Globulin
Ly
C1
Ly
C1
Ly
Ly
Membrane Attack
Complex
Membrane Attack
Complex
Dye
Ly
Ly
Dye
Ly
CD19 or
(B cell)
CD3
(T cell)
Flow Cytometer
% rejection
40%
n=
41
81% vs 83%
1 yr survival
n=
56
Antigen Specific
ELISA
- Yes / No
- PRA % (I & II)
- Specificity (I & II)
FlowPRA
Flow cytometry using
microparticles (beads)
- PRA % (I and II )
- Specificity (I & II)
Multi-plex
- Suspension Arrays
- Protein Chips
Flow Microparticles
One Lambda
www.onelambda.com
B cells + EBV
Class I or II Phenotype
or Individual Molecule
Microparticles
Purified HLA Antigens
Flow Cytometry
ELISA
Microparticles
ELISA
90%
2
160
Flow PRA-Positive
7
34
NEGATIVE
CDC
102
162
AHG-CDC
116
(+13%)
148
ELISA
127
(+10%)
137
FlowPRA
139
(+10%)
125
% Graft
Survival
30
20
12
20
Bray RA, Nickerson PW, Kerman RH, Gebel HM. Immunol Res. 29:41, 2004
Surviving
P > 0.05
N = 372
N= 492
N = 120
Cutpoint = 30%
2
3
4
Follow-up (years)
Submitted for publication
High
Low
Crossmatch
Low Risk
Antibody Negative
Crossmatch Negative
Antibody Negative
Antibody Positive
Crossmatch Positive
Crossmatch Negative
High Risk
Antibody Positive
Crossmatch Positive
PRA
PRA can be a qualitative and/or quantitative
assessment of alloimmunization in transplant
patients.
Optimally, PRA testing should identify the
specificity of an antibody and provide the
transplantability index of a patient.
More succinctly, PRA testing should correlate
with the final crossmatch.
Rejection
Time to
Ab mediated
Time to
First
Month
14/15
(93%)
Rejection
6 (1-17)
Graft
Loss
4 (27%)
Graft
Loss
4 (1-14)
8/10 (80%)
5 (2-7)
HLA Ab (non-donor)
3/21 (14%)
13 (13-19)
3 (30%)
0 (0%)
5 (2-9)
NA
Approaches
Pharmacological
Desensitization
IVIG
PP / IVIG
Rituxan
Transplant across a +
crossmatch anticipating
Immunosuppression
Biological
Identical Sibling
Xenotransplantation
Acceptable Mismatch
- Detailed Antibody Analysis
- Comprehensive PRA
- Virtual Crossmatch
Acceptable Mismatches
Putative Recipient:
A1, A30; B7, B8 ; DR11, 15
Antibodies - A2, 23, 24, 68
Potential Donor:
A25, A33; B42, B18; DR12, DR13
Strategic Approaches
- Based on recognition that matching is not for
everyone- 85% of DD Txs are mismatched.
- Focus on appropriate mismatching rather
than looking for an HLA match.
- Requires detailed evaluation of the
patients HLA antibodies.
- Shifts emphasis to antibody evaluation
and away from crossmatching to identify
acceptable mismatches.
END OF LECTURE