Prospective monitoring of donor-specific anti-HLA antibodies after intestine/multivisceral transplantation: Significance of De novo antibodies

Chandrashekhar Kubal, Richard Mangus, Romil Saxena, Andrew Lobashevsky, Nancy Higgins, Jonathan Fridell, A. Joseph Tector

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background. Presence of circulating donor-specific antibodies (DSA) may be associated with worse clinical outcomes after intestine/multivisceral transplantation. Methods. In 79 intestine/multivisceral recipients, sera were prospectively screened for DSA by Luminex Single antigen test at 1, 3, 6, 9, 12, 18, 24, and 36 months after transplantation. Standard immunosuppression included thymoglobulin-rituximab induction and tacrolimus-prednisone maintenance. C4d staining was performed retrospectively on biopsies in patients that developed acute rejection (AR). Results. Twenty-two (28%) patients developed de novo DSA at a median posttransplant period of 3 (1-36) months. De novo DSA were observed in 10 of 40 liver-including and 12 of 39 liverexcluding transplants (P = 0.57). Occurrence of AR was slightly higher in patients with de novo DSA (45% vs 33%, respectively; P = 0.41). Similarly, chronic rejection (14% vs 5%; P = 0.21) and graft loss due to AR (18% vs 7%; P = 0.14) were numerically higher in patients with de novo DSA. Only 35% patients experiencing AR had circulating de novo DSA at the time of AR. Antibodymediated rejectionwas diagnosed in 6 patients based on C4d staining, of these 2 patients had circulating de novo DSA at the time of biopsy. Conclusions. De novo DSA formation, particularly early in the posttransplant course may be associated with trends toward worse outcomes. However, its significance in the pathophysiology of AR remains uncertain. Studies focusingmechanisms of DSA-related graft injury and intragraft DSA detection might provide further insight into this issue.

Original languageEnglish (US)
Pages (from-to)e49-e56
JournalTransplantation
Volume99
Issue number8
DOIs
StatePublished - Aug 1 2015

Fingerprint

Intestines
Anti-Idiotypic Antibodies
Transplantation
Tissue Donors
Antibodies
Transplants
Staining and Labeling
Biopsy
Tacrolimus
Prednisone
Immunosuppression
Antibody Formation
Maintenance
Antigens
Liver
Wounds and Injuries
Serum

ASJC Scopus subject areas

  • Transplantation

Cite this

Prospective monitoring of donor-specific anti-HLA antibodies after intestine/multivisceral transplantation : Significance of De novo antibodies. / Kubal, Chandrashekhar; Mangus, Richard; Saxena, Romil; Lobashevsky, Andrew; Higgins, Nancy; Fridell, Jonathan; Tector, A. Joseph.

In: Transplantation, Vol. 99, No. 8, 01.08.2015, p. e49-e56.

Research output: Contribution to journalArticle

Kubal, Chandrashekhar ; Mangus, Richard ; Saxena, Romil ; Lobashevsky, Andrew ; Higgins, Nancy ; Fridell, Jonathan ; Tector, A. Joseph. / Prospective monitoring of donor-specific anti-HLA antibodies after intestine/multivisceral transplantation : Significance of De novo antibodies. In: Transplantation. 2015 ; Vol. 99, No. 8. pp. e49-e56.
@article{ccb13649b7c04c729bd1bdf2afa0443e,
title = "Prospective monitoring of donor-specific anti-HLA antibodies after intestine/multivisceral transplantation: Significance of De novo antibodies",
abstract = "Background. Presence of circulating donor-specific antibodies (DSA) may be associated with worse clinical outcomes after intestine/multivisceral transplantation. Methods. In 79 intestine/multivisceral recipients, sera were prospectively screened for DSA by Luminex Single antigen test at 1, 3, 6, 9, 12, 18, 24, and 36 months after transplantation. Standard immunosuppression included thymoglobulin-rituximab induction and tacrolimus-prednisone maintenance. C4d staining was performed retrospectively on biopsies in patients that developed acute rejection (AR). Results. Twenty-two (28{\%}) patients developed de novo DSA at a median posttransplant period of 3 (1-36) months. De novo DSA were observed in 10 of 40 liver-including and 12 of 39 liverexcluding transplants (P = 0.57). Occurrence of AR was slightly higher in patients with de novo DSA (45{\%} vs 33{\%}, respectively; P = 0.41). Similarly, chronic rejection (14{\%} vs 5{\%}; P = 0.21) and graft loss due to AR (18{\%} vs 7{\%}; P = 0.14) were numerically higher in patients with de novo DSA. Only 35{\%} patients experiencing AR had circulating de novo DSA at the time of AR. Antibodymediated rejectionwas diagnosed in 6 patients based on C4d staining, of these 2 patients had circulating de novo DSA at the time of biopsy. Conclusions. De novo DSA formation, particularly early in the posttransplant course may be associated with trends toward worse outcomes. However, its significance in the pathophysiology of AR remains uncertain. Studies focusingmechanisms of DSA-related graft injury and intragraft DSA detection might provide further insight into this issue.",
author = "Chandrashekhar Kubal and Richard Mangus and Romil Saxena and Andrew Lobashevsky and Nancy Higgins and Jonathan Fridell and Tector, {A. Joseph}",
year = "2015",
month = "8",
day = "1",
doi = "10.1097/TP.0000000000000614",
language = "English (US)",
volume = "99",
pages = "e49--e56",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "8",

}

TY - JOUR

T1 - Prospective monitoring of donor-specific anti-HLA antibodies after intestine/multivisceral transplantation

T2 - Significance of De novo antibodies

AU - Kubal, Chandrashekhar

AU - Mangus, Richard

AU - Saxena, Romil

AU - Lobashevsky, Andrew

AU - Higgins, Nancy

AU - Fridell, Jonathan

AU - Tector, A. Joseph

PY - 2015/8/1

Y1 - 2015/8/1

N2 - Background. Presence of circulating donor-specific antibodies (DSA) may be associated with worse clinical outcomes after intestine/multivisceral transplantation. Methods. In 79 intestine/multivisceral recipients, sera were prospectively screened for DSA by Luminex Single antigen test at 1, 3, 6, 9, 12, 18, 24, and 36 months after transplantation. Standard immunosuppression included thymoglobulin-rituximab induction and tacrolimus-prednisone maintenance. C4d staining was performed retrospectively on biopsies in patients that developed acute rejection (AR). Results. Twenty-two (28%) patients developed de novo DSA at a median posttransplant period of 3 (1-36) months. De novo DSA were observed in 10 of 40 liver-including and 12 of 39 liverexcluding transplants (P = 0.57). Occurrence of AR was slightly higher in patients with de novo DSA (45% vs 33%, respectively; P = 0.41). Similarly, chronic rejection (14% vs 5%; P = 0.21) and graft loss due to AR (18% vs 7%; P = 0.14) were numerically higher in patients with de novo DSA. Only 35% patients experiencing AR had circulating de novo DSA at the time of AR. Antibodymediated rejectionwas diagnosed in 6 patients based on C4d staining, of these 2 patients had circulating de novo DSA at the time of biopsy. Conclusions. De novo DSA formation, particularly early in the posttransplant course may be associated with trends toward worse outcomes. However, its significance in the pathophysiology of AR remains uncertain. Studies focusingmechanisms of DSA-related graft injury and intragraft DSA detection might provide further insight into this issue.

AB - Background. Presence of circulating donor-specific antibodies (DSA) may be associated with worse clinical outcomes after intestine/multivisceral transplantation. Methods. In 79 intestine/multivisceral recipients, sera were prospectively screened for DSA by Luminex Single antigen test at 1, 3, 6, 9, 12, 18, 24, and 36 months after transplantation. Standard immunosuppression included thymoglobulin-rituximab induction and tacrolimus-prednisone maintenance. C4d staining was performed retrospectively on biopsies in patients that developed acute rejection (AR). Results. Twenty-two (28%) patients developed de novo DSA at a median posttransplant period of 3 (1-36) months. De novo DSA were observed in 10 of 40 liver-including and 12 of 39 liverexcluding transplants (P = 0.57). Occurrence of AR was slightly higher in patients with de novo DSA (45% vs 33%, respectively; P = 0.41). Similarly, chronic rejection (14% vs 5%; P = 0.21) and graft loss due to AR (18% vs 7%; P = 0.14) were numerically higher in patients with de novo DSA. Only 35% patients experiencing AR had circulating de novo DSA at the time of AR. Antibodymediated rejectionwas diagnosed in 6 patients based on C4d staining, of these 2 patients had circulating de novo DSA at the time of biopsy. Conclusions. De novo DSA formation, particularly early in the posttransplant course may be associated with trends toward worse outcomes. However, its significance in the pathophysiology of AR remains uncertain. Studies focusingmechanisms of DSA-related graft injury and intragraft DSA detection might provide further insight into this issue.

UR - http://www.scopus.com/inward/record.url?scp=84940697207&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940697207&partnerID=8YFLogxK

U2 - 10.1097/TP.0000000000000614

DO - 10.1097/TP.0000000000000614

M3 - Article

C2 - 25769071

AN - SCOPUS:84940697207

VL - 99

SP - e49-e56

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 8

ER -