BACKGROUND: Acute rejection (AR) associated with de novo production of donor-specific antibodies (DSA) is a clinicopathological entity that carries a poor prognosis (acute humoral rejection, AHR). The aim of this study was to determine the incidence and clinical characteristics of AHR in renal allograft recipients, and to further analyze the antibodies involved. METHODS: During a 4-year period, 232 renal transplants (Tx) were performed at our institution. Assays for DSA included T and B cell cytotoxic and/or flow cytometric cross-matches and cytotoxic antibody screens (PRA). C4d complement staining was performed on frozen biopsy tissue. RESULTS: A total of 81 patients (35%) suffered at least one episode of AR within the first 3 months: 51 had steroid-insensitive AR whereas the remaining 30 had steroid-sensitive AR. No DSA were found in patients with steroid-sensitive AR. In contrast, circulating DSA were found in 19/51 patients (37%) with steroid-insensitive AR, and widespread C4d deposits in peritubular capillaries were present in 18 of these 19 (95%). In at least three cases, antibodies were against donor HLA class II antigens. DSA were not found in the remaining 32 patients but C4d staining was positive in 2 of 32. The DSA/C4d positive (n=18) and DSA/C4d negative (n=30) groups differed in pre-Tx PRA levels, percentage of re-Tx patients, refractoriness to antilymphocyte therapy, and outcome. Plasmapheresis and tacrolimus-mycophenolate mofetil rescue reversed rejection in 9 of 10 recipients with refractory AHR. CONCLUSION: More than one-third of the patients with steroid-insensitive AR had evidence of AHR, often resistant to antilymphocyte therapy. Most cases (95%) with DSA at the time of rejection had widespread C4d deposits in peritubular capillaries, suggesting a pathogenic role of the circulating alloantibody. Combined DSA testing and C4d staining provides a useful approach for the early diagnosis of AHR, a condition that often necessitates a more intensive therapeutic rescue regimen.
BACKGROUND: Acute rejection (AR) associated with de novo production of donor-specific antibodies (DSA) is a clinicopathological entity that carries a poor prognosis (acute humoral rejection, AHR). The aim of this study was to determine the incidence and clinical characteristics of AHR in renal allograft recipients, and to further analyze the antibodies involved. METHODS: During a 4-year period, 232 renal transplants (Tx) were performed at our institution. Assays for DSA included T and B cell cytotoxic and/or flow cytometric cross-matches and cytotoxic antibody screens (PRA). C4d complement staining was performed on frozen biopsy tissue. RESULTS: A total of 81 patients (35%) suffered at least one episode of AR within the first 3 months: 51 had steroid-insensitive AR whereas the remaining 30 had steroid-sensitive AR. No DSA were found in patients with steroid-sensitive AR. In contrast, circulating DSA were found in 19/51 patients (37%) with steroid-insensitive AR, and widespread C4d deposits in peritubular capillaries were present in 18 of these 19 (95%). In at least three cases, antibodies were against donor HLA class II antigens. DSA were not found in the remaining 32 patients but C4d staining was positive in 2 of 32. The DSA/C4d positive (n=18) and DSA/C4d negative (n=30) groups differed in pre-Tx PRA levels, percentage of re-Tx patients, refractoriness to antilymphocyte therapy, and outcome. Plasmapheresis and tacrolimus-mycophenolate mofetil rescue reversed rejection in 9 of 10 recipients with refractory AHR. CONCLUSION: More than one-third of the patients with steroid-insensitive AR had evidence of AHR, often resistant to antilymphocyte therapy. Most cases (95%) with DSA at the time of rejection had widespread C4d deposits in peritubular capillaries, suggesting a pathogenic role of the circulating alloantibody. Combined DSA testing and C4d staining provides a useful approach for the early diagnosis of AHR, a condition that often necessitates a more intensive therapeutic rescue regimen.
Authors: Hong Xu; Paula M Chilton; Michael K Tanner; Yiming Huang; Carrie L Schanie; Mariano Dy-Liacco; Jun Yan; Suzanne T Ildstad Journal: Blood Date: 2006-08-03 Impact factor: 22.113
Authors: Ek Khoon Tan; Andrew Bentall; Patrick G Dean; Mohammed F Shaheen; Mark D Stegall; Carrie A Schinstock Journal: Transplantation Date: 2019-11 Impact factor: 4.939
Authors: Julio Pascual; Milagros D Samaniego; José R Torrealba; Jon S Odorico; Arjang Djamali; Yolanda T Becker; Barbara Voss; Glen E Leverson; Stuart J Knechtle; Hans W Sollinger; John D Pirsch Journal: J Am Soc Nephrol Date: 2008-01-30 Impact factor: 10.121
Authors: Antoine Durrbach; Helene Francois; Severine Beaudreuil; Antoine Jacquet; Bernard Charpentier Journal: Nat Rev Nephrol Date: 2010-02-02 Impact factor: 28.314
Authors: Nicolas Kozakowski; Harald Herkner; Georg A Böhmig; Heinz Regele; Christoph Kornauth; Gregor Bond; Željko Kikić Journal: Kidney Int Date: 2015-03-04 Impact factor: 10.612
Authors: Laurie D Snyder; Ziwei Wang; Dong-Feng Chen; Nancy L Reinsmoen; C Ashley Finlen-Copeland; W Austin Davis; David W Zaas; Scott M Palmer Journal: Chest Date: 2013-07 Impact factor: 9.410
Authors: B Gao; C Moore; F Porcheray; C Rong; C Abidoglu; J DeVito; R Paine; T C Girouard; S L Saidman; D Schoenfeld; B Levin; W Wong; N Elias; C Schuetz; I Rosales; Y Fu; E Zorn Journal: Am J Transplant Date: 2014-06-16 Impact factor: 8.086
Authors: Alice Bickerstaff; Ronald Pelletier; Jiao-Jing Wang; Gyongyi Nadasdy; Nicholas DiPaola; Charles Orosz; Anjali Satoskar; Gregg Hadley; Tibor Nadasdy Journal: Am J Pathol Date: 2008-06-26 Impact factor: 4.307
Authors: Matthew M DeNicola; Sam S Weigt; John A Belperio; Elaine F Reed; David J Ross; W Dean Wallace Journal: J Heart Lung Transplant Date: 2013-01-10 Impact factor: 10.247