Evaluation of serial monitoring of donor-specific antibodies in pediatric and adult intestinal/multivisceral transplant recipients.
antibody-mediated rejection
donor-specific antibodies
intestinal (allograft) function/dysfunction
intestinal transplantation
monitoring: Immune
multivisceral transplantation
Journal
Pediatric transplantation
ISSN: 1399-3046
Titre abrégé: Pediatr Transplant
Pays: Denmark
ID NLM: 9802574
Informations de publication
Date de publication:
09 Nov 2023
09 Nov 2023
Historique:
revised:
23
08
2023
received:
15
06
2023
accepted:
24
10
2023
medline:
9
11
2023
pubmed:
9
11
2023
entrez:
9
11
2023
Statut:
aheadofprint
Résumé
The study purpose was to add to limited literature assessing anti-HLA donor-specific antibody (DSA) appearance, clearance, specificity, and impact in intestinal/multivisceral (MV) transplant as well as the value of serial monitoring following an institutional protocol shift implementing serial monitoring. This single-center retrospective review included intestinal/MV recipients transplanted 1/1/15-9/31/17 with completed DSA testing. Patients were divided into groups based on DSA presence post-transplant. The primary outcome was biopsy-proven acute rejection (BPAR). Secondary outcomes included graft loss and death. Descriptive analysis of DSA was completed. Of the 35 intestinal/MV recipients (60% pediatric) with DSA testing, 24 patients had post-transplant DSA. Fifteen patients in the DSA(+) group had T-cell-mediated BPAR versus five in the DSA(-) group (63% vs 45%, p = .47). Days to BPAR were 25 [IQR 19-165] (DSA(+) group) versus 232 [IQR 25.5-632.5] (DSA(-) group) (p = .066). There were no differences between groups for graft loss or death. One hundred and five DSA were identified in the DSA(+) group with 63% being class II, and 54% cleared during follow-up. DSA were directed against 50 different HLA alleles, with the most common being directed against HLA- DQ (35%). Time to first DSA and to clearance did not differ between class I and II. Findings confirm previous data that suggest post-transplant DSA in this population may lead to increased BPAR or shorter time to BPAR, although not statistically significant. Most DSA were identified within the first month after transplant, and ahead of rejection identification on biopsy. DSA therefore may have utility as an early rejection biomarker and use may be considered in place of early protocol biopsies, particularly in pediatric patients. We identified novel findings of DSA directed against a large breadth of HLA in intestinal/MV patients.
Sections du résumé
BACKGROUND
BACKGROUND
The study purpose was to add to limited literature assessing anti-HLA donor-specific antibody (DSA) appearance, clearance, specificity, and impact in intestinal/multivisceral (MV) transplant as well as the value of serial monitoring following an institutional protocol shift implementing serial monitoring.
METHODS
METHODS
This single-center retrospective review included intestinal/MV recipients transplanted 1/1/15-9/31/17 with completed DSA testing. Patients were divided into groups based on DSA presence post-transplant. The primary outcome was biopsy-proven acute rejection (BPAR). Secondary outcomes included graft loss and death. Descriptive analysis of DSA was completed.
RESULTS
RESULTS
Of the 35 intestinal/MV recipients (60% pediatric) with DSA testing, 24 patients had post-transplant DSA. Fifteen patients in the DSA(+) group had T-cell-mediated BPAR versus five in the DSA(-) group (63% vs 45%, p = .47). Days to BPAR were 25 [IQR 19-165] (DSA(+) group) versus 232 [IQR 25.5-632.5] (DSA(-) group) (p = .066). There were no differences between groups for graft loss or death. One hundred and five DSA were identified in the DSA(+) group with 63% being class II, and 54% cleared during follow-up. DSA were directed against 50 different HLA alleles, with the most common being directed against HLA- DQ (35%). Time to first DSA and to clearance did not differ between class I and II.
CONCLUSION
CONCLUSIONS
Findings confirm previous data that suggest post-transplant DSA in this population may lead to increased BPAR or shorter time to BPAR, although not statistically significant. Most DSA were identified within the first month after transplant, and ahead of rejection identification on biopsy. DSA therefore may have utility as an early rejection biomarker and use may be considered in place of early protocol biopsies, particularly in pediatric patients. We identified novel findings of DSA directed against a large breadth of HLA in intestinal/MV patients.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14638Informations de copyright
© 2023 Wiley Periodicals LLC.
Références
Grant D, Abu-Elmagd K, Mazariegos G, et al. Intestinal/MV transplant registry report: global activity and trends. Am J Transplant. 2015;15:210-219.
Abu-Elmagd KM, Costa G, Bond GJ, et al. Five hundred intestinal/MV and multivisceral transplantations at a single center: major advances with new challenges. Ann Surg. 2009;250:567-581.
Dick AAS, Horslen S. Antibody-mediated rejection after intestinal transplantation. Curr Opin Organ Transplant. 2012;17(3):250-257.
Hawksworth JS, Matsumoto CS. Donor-specific antibody management in intestine transplantation: hope for improving the long-term durability of the intestine allograft? Curr Opin Organ Transplant. 2019;24(2):212-218.
Troxell ML, Higgins JP, Kambham N. Evaluation of C4d staining in liver and small intestine allografts. Arch Pathol Lab Med. 2006;130:1489-1496.
de Serre NP, Canioni D, Lacaille F, et al. Evaluation of c4d deposition and circulating antibody in small bowel transplantation. Am J Transplant. 2008;8:1290-1296.
Tsai HL, Island ER, Chang JW, et al. Association between donor-specific antibodies and acute rejection and resolution in small bowel and multivisceral transplantation. Transplantation. 2011;92:709-715.
Abu-Elmagd KM, Wu G, Costa G, et al. Preformed and de novo donor specific antibodies in visceral transplantation: long-term outcome with special reference to the liver. Am J Transplant. 2012;12:3047-3060.
Farmer DG, Venick RS, Colangelo J, et al. Pretransplant predictors of survival after intestinal/MV transplantation: analysis of a single-center experience of more than 100 transplants. Transplantation. 2010;90:1574-1580.
Gerlach UA, Schoenemann C, Lachmann N, Koch M, Pascher A. Salvage therapy for refractory rejection and persistence of donor-specific antibodies after intestinal/MV transplantation using the proteasome inhibitor bortezomib. Transpl Int. 2011;24:e43-e45.
Kubal C, Mangus R, Saxena R, et al. Prospective monitoring of donor-specific anti-HLA antibodies after intestine/multivisceral transplantation: significance of De novo antibodies. Transplantation. 2015;99(8):e49-e56.
Cheng EY, Everly MJ, Kaneku H, et al. Prevalence and clinical impact of donor-specific alloantibody among intestinal transplant recipients. Transplantation. 2017;101(4):873-882.
Petit LM, Rabant M, Canioni D, et al. Impacts of donor-specific anti-HLA antibodies and antibody-mediated rejection on outcomes after intestinal transplantation in children. Pediatr Transplantation. 2017;21(2):e12847.
Rabant M, Racapé M, Petit LM, et al. Antibody-mediated rejection in pediatric small bowel transplantation: Capillaritis is a major determinant of C4d positivity in intestinal transplant biopsies. Am J Transplant. 2018;18(9):2250-2260.
Wu T, Abu-Elmagd K, Bond G, Demetris AJ. A clinicopathologic study of isolated intestinal/MV allografts with preformed IgG lymphocytotoxic antibodies. Hum Pathol. 2004;35:1332-1339.
DeVos JM, Gaber AO, Knight RJ, et al. Donor-specific HLA-DQ antibodies may contribute to poor graft outcome after renal transplantation. Kidney Int. 2012;82(5):598-604.
Tikkanen JM, Singer LG, Kim SJ, et al. De novo dq donor-specific antibodies are associated with chronic lung allograft dysfunction after lung transplantation. Am J Respir Crit Care Med. 2016;194(5):596-606.
Kasiske BL, Zeier MG, Chapman JR, et al. KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary. Kidney Int. 2010;77(4):299-311.