Abstract
We have reported that B6.CCR5-/- mice reject renal allografts with high serum donor-specific antibody (DSA) titers and marked C4d deposition in grafts, features consistent with antibody-mediated rejection (AMR). B6.huCD20/CCR5-/- mice, where human CD20 expression is restricted to B cells, rejected A/J renal allografts by day 26 posttransplant with DSA first detected in serum on day 5 posttransplant and increased thereafter. Recipient treatment with anti-huCD20 mAb prior to the transplant and weekly up to 7 weeks posttransplant promoted long-term allograft survival (>100 days) with low DSA titers. To investigate the effect of B cell depletion at the time serum DSA was first detected, recipients were treated with anti-huCD20 mAb on days 5, 8, and 12 posttransplant. This regimen significantly reduced DSA titers and graft inflammation on day 15 posttransplant and prolonged allograft survival >60 days. However, DSA returned to the titers observed in control treated recipients by day 30 posttransplant and histological analyses on day 60 posttransplant indicated severe interstitial fibrosis. These results indicate that anti-huCD20 mAb had the greatest effect as a prophylactic treatment and that the distinct kinetics of DSA responses accounts for acute renal allograft failure versus the development of fibrosis.
Original language | English (US) |
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Pages (from-to) | 1192-1204 |
Number of pages | 13 |
Journal | American Journal of Transplantation |
Volume | 15 |
Issue number | 5 |
DOIs | |
State | Published - May 1 2015 |
Externally published | Yes |
Keywords
- alloantibody
- B cell specific
- chronic
- fusion proteins and monoclonal antibodies
- immunosuppressant
- kidney disease: immune/inflammatory
- rejection
- rejection: antibody-mediated (ABMR)
ASJC Scopus subject areas
- Transplantation
- Immunology and Allergy
- Pharmacology (medical)