Incidence and Impact of De Novo Donor-Specific Alloantibody in Primary Renal Allografts

Everly, Matthew J; Rebellato, Lorita M.; Haisch, Carl E.; Ozawa, Miyuki; Parker, Kathryn; Briley, Kimberly P.; Catrou, Paul G.; Bolin, Paul; Kendrick, W.; Kendrick, Scott A.; Harland, Robert C.; Terasaki, Paul I.

doi:10.1097/tp.0b013e31827d62e3

Cited by 340 publications

(337 citation statements)

References 28 publications

(11 reference statements)

Supporting

Mentioning

292

Contrasting

Unclassified

Order By: Relevance

“…Approximately 11% of kidney‐transplant recipients develop de novo DSAs within the first year after transplantation; this proportion increases to 20% by 5 years posttransplant 7. The risk of antibody‐mediated rejection and graft loss increases with higher mean fluorescence intensity (MFI), a semi‐quantitative measure of the number of DSAs circulating in patient sera 8…”

Section: Introductionmentioning

confidence: 99%

De novo donor-specific antibodies in belatacept-treated vs cyclosporine-treated kidney-transplant recipients: Post hoc analyses of the randomized phase III BENEFIT and BENEFIT-EXT studies

Bray

Gebel

Townsend

et al. 2018

American Journal of Transplantation

View full text Add to dashboard Cite

Donor‐specific antibodies (DSAs) are associated with an increased risk of antibody‐mediated rejection and graft failure. In BENEFIT and BENEFIT‐EXT, kidney‐transplant recipients were randomized to receive belatacept more intense (MI)–based, belatacept less intense (LI)–based, or cyclosporine‐based immunosuppression for up to 7 years (84 months). The presence/absence of HLA‐specific antibodies was determined at baseline, at months 6, 12, 24, 36, 48, 60, and 84, and at the time of clinically suspected episodes of acute rejection, using solid‐phase flow‐cytometry screening. Samples from anti‐HLA‐positive patients were further tested with a single‐antigen bead assay to determine antibody specificities, presence/absence of DSAs, and mean fluorescence intensity (MFI) of any DSAs present. In BENEFIT, de novo DSAs developed in 1.4%, 3.5%, and 12.1% of belatacept MI‐treated, belatacept LI‐treated, and cyclosporine‐treated patients, respectively. The corresponding values in BENEFIT‐EXT were 3.8%, 1.1%, and 11.2%. Per Kaplan‐Meier analysis, de novo DSA incidence was significantly lower in belatacept‐treated vs cyclosporine‐treated patients over 7 years in both studies (P < .01). In patients who developed de novo DSAs, belatacept‐based immunosuppression was associated with numerically lower MFI vs cyclosporine‐based immunosuppression. Although derived post hoc, these data suggest that belatacept‐based immunosuppression suppresses de novo DSA development more effectively than cyclosporine‐based immunosuppression.

show abstract

Section: Introductionmentioning

confidence: 99%

De novo donor-specific antibodies in belatacept-treated vs cyclosporine-treated kidney-transplant recipients: Post hoc analyses of the randomized phase III BENEFIT and BENEFIT-EXT studies

Bray

Gebel

Townsend

et al. 2018

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…[18][19][20] However, these percentages should be interpreted with caution. During the last 10 years, assays for the detection of anti-HLA antibodies have evolved from complement-dependent cytotoxicity to the highly sensitive microbead-based Luminex assay.…”

Section: Incidence and Risk Factors For Sensitizationmentioning

confidence: 99%

Effect of Immunosuppressive Drugs on Humoral Allosensitization after Kidney Transplant

Thaunat

Koenig

Leibler³

et al. 2016

JASN

View full text Add to dashboard Cite

The negative effect of donor-specific antibodies on the success of solid transplant is now clearly established. However, the lack of effective treatment to prevent the development of antibody-mediated lesions deepens the need for clinicians to focus on primary prevention of de novo humoral allosensitization. Among the factors associated with the risk of developing de novo donor-specific antibodies, therapeutic immunosuppression is the most obvious parameter in which improvement is possible. Beyond compliance and the overall depth of immunosuppression, it is likely that the nature of the drugs is also crucial. Here, we provide an overview of the molecular effect of the various immunosuppressive drugs on B cell biology. Clinical data related to the effect of these drugs on de novo humoral allosensitization are also examined, providing a platform from which clinicians can optimize immunosuppression for prevention of de novo donor-specific antibody generation at the individual level.

show abstract

“…17 The development of de novo donor-specific antibodies (DSAs) after transplant is now a widely used harbinger of subclinical alloreactivity and often precedes overt antibodymediated rejection by months to years. 18,19 We hypothesized that persistent BK viremia is a risk factor for and precedes the development of DSAs.…”

mentioning

confidence: 99%

Persistent BK Viremia Does Not Increase Intermediate-Term Graft Loss but Is Associated with De Novo Donor-Specific Antibodies

Sawinski¹,

Forde²,

Trofe‐Clark³

et al. 2015

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

There are limited data regarding intermediate-term outcomes in patients with persistent BK viremia. Other viral infections have been implicated in the development of allosensitization through heterologous immunity, but the relationship between BK viremia and donor-specific antibodies (DSAs) is unexplored. In 2008, we initiated routine post-transplant BK viremia and DSA screening at our center; 785 kidney or kidney-pancreas transplant recipients were included in our study. Of these recipients, 132 (17%) recipients developed BK viremia during the study period. The median duration of BK viremia was 140 days (interquartile range=40-393 days), and persistent BK viremia was defined as lasting $140 days. Kaplan-Meier curves were generated to assess differences in patient and allograft survival on the basis of BK viremia status; survival was modeled using Cox proportional hazard regression. After a median follow-up of 3 years, there was no significant difference in terms of patient (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.28 to 2.49) or allograft survival (HR, 0.80; 95% CI, 0.37 to 1.73) between patients with and without BK viremia, which was confirmed in a time-varying analysis. In our logistic regression model, persistent BK viremia was strongly associated with the development of class II (HR, 2.55; 95% CI, 1.30 to 4.98) but not class I (HR, 1.13; 95% CI, 0.46 to 2.77) DSAs. These data suggest that persistent BK viremia does not negatively affect intermediate-term patient or allograft survival but is associated with increased risk for de novo DSA, although the exact mechanism is unclear.

show abstract

Incidence and Impact of De Novo Donor-Specific Alloantibody in Primary Renal Allografts

Cited by 340 publications

References 28 publications

De novo donor-specific antibodies in belatacept-treated vs cyclosporine-treated kidney-transplant recipients: Post hoc analyses of the randomized phase III BENEFIT and BENEFIT-EXT studies

De novo donor-specific antibodies in belatacept-treated vs cyclosporine-treated kidney-transplant recipients: Post hoc analyses of the randomized phase III BENEFIT and BENEFIT-EXT studies

Effect of Immunosuppressive Drugs on Humoral Allosensitization after Kidney Transplant

Persistent BK Viremia Does Not Increase Intermediate-Term Graft Loss but Is Associated with De Novo Donor-Specific Antibodies

Contact Info

Product

Resources

About