Antibody Mediated Rejection in Heart & Lung Transplantation

*Product Information

Product Description Cat Id Tests

LABScreen® Single Antigen (For In Vitro Diagnostic Use.)

LABScreen Single Antigen HLA Class I - Combi LS1A04 25 tests
LABScreen Single Antigen HLA Class II - Group 1 LS2A01 25 tests

LABScreen® Single Antigen Supplement (For In Vitro Diagnostic Use.)

LABScreen Single Antigen Class I - Supplement (Group1) LS1ASP01 25 tests
LABScreen Single Antigen Class II - Supplement (Group1) LS2ASP01 25 tests

C1qScreen™ (For In Vitro Diagnostic Use. (European Union Only))

C1qScreen™ C1Q 25 tests
C1qScreen Class I Positive Control C1QS-PC1 20 tests
C1qScreen Negative Control Serum C1QS-NC 20 tests
C1qScreen Class II Positive Control C1QS-PC2 20 tests

References

1. Loupy A, Toquet C, Rouvier P, Beuscart T, Bories MC, Varnous S, Guillemain R, Pattier S, Suberbielle C, Leprince P, Lefaucheur C,
Jouven X, Bruneval P, Duong Van Huyen JP. Late Failing Heart Allografts: Pathology of Cardiac Allograft Vasculopathy and Association with
Antibody-Mediated Rejection. Am J Transplant, 16(1):111-20, 2016.
2. Reinsmoen NL, Patel J, Mirocha J, Lai CH, Naim M, Ong G, Wang Q, Zhang X, Liou F, Yu Z2, Kobashigawa J. Optimizing transplantation
of sensitized heart candidates using 4 antibody detection assays to prioritize the assignment of unacceptable antigens. J Heart Lung
Transplant, 35(2):165-72, 2016.
3. Tran A, Fixler D, Huang R, Meza T, Lacelle C, Das BB. Donor-specific HLA alloantibodies: Impact on cardiac allograft vasculopathy,
rejection, and survival after pediatric heart transplantation. Heart Lung Transplant, 35(1):87-91, 2015.
4. Irving CA, Carter V, Gennery AR, Parry G, Griselli M, Hasan A, Kirk CR. Effect of persistent versus transient donor-specific HLA antibodies
on graft outcomes in pediatric cardiac transplantation. J Heart Lung Transplant, 34(10):1310-7, 2015.
5. Godown J, Slaughter JC, Fossey SC, McKane M, Dodd DA. Risk factors for the development of donor-specific antibodies after pediatric
heart transplantation. Pediatr Transplant, 19(8):906-10, 2015.
6. Roux A, Bendib Le Lan I, Holifanjaniaina S, Thomas KA, Hamid AM, Picard C, Grenet D, De Miranda S, Douvry B, Beaumont-Azuar L,
Sage E, Devaquet J, Cuquemelle E, Le Guen M, Spreafico R, Suberbielle-Boissel C, Stern M, Parquin F. Antibody-Mediated Rejection in
Lung Transplantation: Clinical Outcomes and Donor-Specific Antibody Characteristics. Am J Transplant, 16(4):1216-28, 2016.
7. Levine DJ, Glanville AR, Aboyoun C, Belperio J, Benden C, Berry GJ, Hachem R, Hayes D, Neil D, Reinsmoen NL, Snyder LD, Sweet S, Figure 1. Explanted cardiac allograft phenotypes according to cluster, a principal component analyses (PCA). A. Individual
Tyan D, Verleden G, Westall G, Yusen RD, Zamora M, Zeevi A. Antibody-mediated rejection of the lung: A consensus report of the overview of morphological and immunological profiles of falling allografts according to unsupervised cluster analysis. Each
International Society for Heart and Lung Transplantation. J Heart Lung Transplant, 35(4):397-406, 2016. variable in an individual patient is colored according to the threshold for each parameter. B. Unsupervised PCA of failing
8. Frost AE, Jammal CT, Cagle PT. Hyperacute rejection following lung transplantation. Chest, 110:559-562, 1996. allografts. The PCA examined 40 failing allografts using seven variables: intimal hyperplasia, media atrophy, media inflamma-
9. Hachem RR. Humoral responses after lung transplantation. Curr Opin Organ Transplant, Epub ahead of print, 2016. tion, endothelitis, microcirculation inflammation, T cell-mediated rejection, and eccentric fibrolipidic plaque. C. The correlation
circle interpreting the meaning of the PC axes shown in the horizontal PC axis shows correlations between media inflammation,
and microcirculation inflammation with intimal hyperplasia and media atrophy. These parameters are opposed (anticorrelated)
*Products not cleared for the treatment or mitigation of AMR.
to eccentric fibrolipidic plaque. Reproduced from: Loupy A, Toquet C, Rouvier P, Beuscart T, Bories MC, Varnous S, Guillemain
R, Pattier S, Suberbielle C, Leprince P, Lefaucheur C, Jouven X, Bruneval P, Duong Van Huyen JP. Late Failing Heart
Allografts: Pathology of Cardiac Allograft Vasculopathy and Association With Antibody-Mediated Rejection. Am J Transplant,
16(1):111-20, 2016.
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 Comprehensive Antibody Testing and Heart Transplantation AMR in Lung Transplantation

Recent studies on the role of donor specific anti-HLA antibod-
Freedom from Antibody-Mediated Rejection by DSA Status ies (DSA) in antibody mediated rejection (AMR) after Heart an
Lung transplantation has brought new insights of mechanisms
Pre-Transplant
and improvements to the use of diagnostic tools for risk strati-
Despite the recognition of AMR as a cause of
Graft Survival and Freedom from CLAD According to DSA Status allograft dysfunction in lung transplantation, the crite-
ria for its diagnosis is not well established. A consen-
A
sus report was recently published by the International
0.0026

1) PRE-TX
fication. Loupy et al. 2016, in an assessment of explanted 100
1.00
HLA-AB NEG/NO DSA
2) PRE-TX
heart allografts for late allograft failure, showed that AMR may 80 Society of Heart and Lung Transplantation (ISHLT) in

Graft Survival
not be the result of a single rejection episode, but instead part
DSA+/XM-
Freedom from AMR by Pretransplant DSA Status

0.75
60 order to initiate criteria for AMR diagnosis after lung
3) PRE-TX
DSA+/XM+ of a dynamic process of continuous and indolent AMR contrib-
40
transplantation and provide more consistency
uting to a chronic form of antibody mediated injury that leads
between study results, improving the knowledge and
0.50

often to late allograft failure. 20

0.25 Figure 2. Freedom from antibody mediated rejection (AMR) by pre-transplant donor specific
0
0 365 730 1095 1460 1825 data for the field. The role of DSA in hyper acute
Time (days)
antibodies (DSA) status. Group 1. HLA-AB neg (human leukocyte antigen – antibody negative)
Overall Log-Rank P = 0.0005 and no DSA, n=270. Group 2. Flow cytometric crossmatch (XM) negative and DSA positive, n=12.
Number of subjects
j at risk rejection after lung transplantation was first reported
DSAposAMRpos 22 15 11 6 3
Group 3. Flow cytometric crossmatch (XM) positive and DSA positive, n=13. Reproduced from:
20 years ago. In a recent study, Roux et al. 2016, by
0.00
0 200 400 600 800 1000 1200 DSAposAMRneg 84 70 43 16 7
Days Post Transplant Reinsmoen NL, Patel J, Mirocha J, Lai CH, Naim M, Ong G, Wang Q, Zhang X, Liou F, Yu Z2,
DSALim 13 13 8 5 2
Kobashigawa J. Optimizing transplantation of sensitized heart candidates using 4 antibody
detection assays to prioritize the assignment of unacceptable antigens. J Heart Lung Transplant,
DSAneg 87 68 44 22 9 frequently monitoring DSA with Single Antigen beads
35(2):165-72, 2016.
B and C4d staining to prospectively diagnose AMR,
< 0.0001
100
was able to show an association of AMR diagnosis in
Reinsmoen et al. 2016, shows an improvement in risk strat-

AD
80
the presence of DSA with the occurrence of chronic

Freedom from CLA

Post-Transplant
ification by identifying an algorithm to optimize transplanta- 60
lung allograft dysfunction and allograft loss.
A
1.00 POST-TX NEGATIVE
tion of sensitized heart candidates through advanced 40

antibody detection methods prioritizing the assignment of

POST-TX PERSISTENT DSA
20
0.75
Figure 4. A. Graft Survival according to antibody mediated rejection (AMR) and
unacceptable antigens (UA). Four antibody detection
POST-TX DE NOVO DSA
0
0 365 730 1095 1460 1825 donor specific antibodies (DSA) status. B. Freedom from Chronic lung allograft
methods were employed: (1) Single antigen beads (SAB),
Time (days)
0.50 dysfunction (CLAD) according to antibody mediated rejection (AMR) and donor
Number of subjects at risk
DSAposAMRpos 15
specific antibodies (DSA) status. DSALIM – DSA limited (DSA with positivity in only
(2) SAB at 1:8 serum dilution, (3) C1q SAB, and (4) CDC
12 8 5 2
DSAposAMRneg one Single Antigen Beads test with MFI between 500-1000). Reproduced from:
0.25 45 44 41 15 7
DSALim Roux A, Bendib Le Lan I, Holifanjaniaina S, Thomas KA, Hamid AM, Picard C,
Overall Log-Rank P < 0.0001
panel. The combination of these methodologies allowed for DSAneg 49
8 8
49
8
40
5
20
2
8 Grenet D, De Miranda S, Douvry B, Beaumont-Azuar L, Sage E, Devaquet J,
Cuquemelle E, Le Guen M, Spreafico R, Suberbielle-Boissel C, Stern M, Parquin F.
strategic prioritization of UA assignment across DSA barri-
0.00
0 200 400 600 800 1000 1200
Days Post Transplant Antibody-Mediated Rejection in Lung Transplantation: Clinical Outcomes and
B
1.00 ers with survival rates comparable to DSA negative heart Donor-Specific Antibody Characteristics. Am J Transplant, 16(4):1216-28, 2016.

POST-TX NEGATIVE transplant recipients. Although there was no difference in

POST-TX PERSISTENT DSA

overall survival based on DSA pre-transplant status in 3

0.75

0.50 years, patients that developed de novo DSA had a higher

incidence of AMR and Cellular Mediated Rejection (CMR).
POST-TX DE NOVO DSA

Those results suggest that post-transplant antibody moni-

0.25

toring is critical for applying immunosuppressive therapies

Overall Log-Rank P < 0.0001
0.00
0 200 400 600 800 1000 1200

early enough to decrease worse impact on graft outcome.

Days Post Transplant
C
1.00 POST-TX PERSISTENT DSA

POST-TX NEGATIVE

0.75 POST-TX DE NOVO DSA

Figure 3. A. Freedom from antibody mediated rejection (AMR) by pre and post-transplant
donor specific antibody (DSA) status. B. Freedom from AMR and cellular mediated rejection
0.50
(CMR) by pre and post-transplant DSA status. C. Overall graft survival by pre and post-trans-
plant DSA status. Groups: POST-TX Negative (no DSA pre or post-transplant) n=249;
0.25 POST-TX Persistent DSA (patients with pre-transplant DSA persistent post-transplant) n=14
and; POST-TX DE NOVO DSA (patients with de novo DSA) n=32. Reproduced from:
Overall Log-Rank P = 0.130 Reinsmoen NL, Patel J, Mirocha J, Lai CH, Naim M, Ong G, Wang Q, Zhang X, Liou F, Yu Z2,
Kobashigawa J. Optimizing transplantation of sensitized heart candidates using 4 antibody
0.00
0 200 400 600 800 1000 1200

detection assays to prioritize the assignment of unacceptable antigens. J Heart Lung

Days Post Transplant

Transplant, 35(2):165-72, 2016.