- 作者：Robert R. Redfield ; Eduardo Rodriguez ; Yanping Luo ; Susan Rostami ; Ronald F. Parsons ; Hooman Noorchashm ; Peter L. Abt ; Ali Naji
- 关键词：Plasma cells ; Donor-specific antibody ; Eosinophils ; Solid organ transplantation ; Desensitization
- 刊名：Journal of Surgical Research
- 出版年：March, 2014
- 年：2014
- 卷：187
- 期：1
- 页码：310-315
- 全文大小：699 K
Background
Long-lived plasma cells (PCs) that form after alloantigen sensitization produce donor-specific alloantibodies that generate a positive serum crossmatch and preclude transplantation. New approaches for desensitization, including PC depletion with proteasome inhibition, show promise but carry considerable toxicity. Recently, eosinophils have been shown to govern PC persistence. Interleukin 5 (IL-5) depletion is known to reduce eosinophils in human asthmatics. We hypothesized that treatment with an anti-IL-5 antibody can deplete alloreactive PCs, reduce donor-specific alloantibodies, and serve as a less toxic alternative to proteasome inhibition.Methods
BALB/c mice were sensitized with B6 skin allografts. Starting at 8聽wk after sensitization, control mice received injections of phosphate-buffered saline, whereas experimental mice received weekly injections of an anti-IL-5 antibody. PCs were enumerated by enzyme-linked immunosorbent spot after 8聽wk.
Results
All control and experimental recipients of skin allografts developed positive crossmatches when screened at 8聽wk after sensitization. All experimental mice treated with anti-IL-5 showed a reduction in their total PC numbers. Also, in contrast to the known adverse effects of proteasome inhibition, experimental mice treated with anti-IL-5 exhibited negligible weight loss or lymphopenia.
Conclusions
Treatment with anti-IL-5 is sufficient to reduce, but not eliminate, alloreactive PCs in the bone marrow. This is because of the targeted reduction of eosinophils leading to a reduction in the PC survival factors a proliferation-inducing ligand and IL-6. Generalized toxicity was not observed in experimental mice. Overall, IL-5 directed immunotherapy can eliminate PC's but is unlikely to be a clinically significant desensitization strategy given the persistence of DSA