Abstract
P614 Background: De novo AHR after kidney Tx has gained much attention during the last few years. The following criteria for AHR are as follows: 1) steroid and anti-lymphocyte therapy resistant acute graft dysfunction; 2) positive cross match; 3) complement deposition in biopsy specimen (Transpl Proc,35,1677,2003). However, involvement of an humoral component in acute rejection after ITx is poorly described and management strategies for this type of rejection are not defined. We report a case of atypical acute rejection after living-donor ITx that is consistent with AHR in kidney Tx. Methods: A 1 year 8 month old patient received a living-donor combined liver/ITx.(liver from father, intestine from aunt) The patient received tacrolimus and steroid-based immunosuppression (IS) plus anti-IL-2 receptor antibody (Ab) induction therapy. When rejection was detected by biopsy, steroid pulse / OKT3 therapy were administered. The serum was examined for flow cytometry cross match (FCXM) using frozen donor lymphocytes. Positive results were confirmed by complement dependent cytotoxicity (CDC). Direct immunofluorescence was performed using anti-IgM, IgG and complement (C4d) Abs to detect immune complexes on the biopsy specimen in situ. Results: Diffuse mucosal denudation was encountered on post-Tx day 12. Since steroid pulse was not effective, OKT3 was started on post-Tx day 14. OKT3 temporarily improved mucosal denudation on post-Tx day 25. However, rejection eventually progressed to complete destruction of the mucosa on post-Tx day 35. During this rejection episode, the number of crypt apoptosis increased but infiltration by blastic lymphocytes (typical feature of acute rejection) was not observed. On post-Tx day 38, the patient suffered from PTLD leading to septicemia and death, despite reduction of IS. FCXM detected the first elevation of serum anti-donor T cell and B cell IgM on post-Tx day 17 (5 days after onset of severe mucosal damage), which was confirmed by CDC. Consistent with FCXM and CDC, direct immunofluorescence first demonstrated endothelial deposition of IgM and C4din the capillaries on the biopsy specimen on post-Tx day16 but not before this timing. Conclusions: 1) Atypical rejection without cell infiltrate was observed in a case of ITx; 2) Serological and pathological evidence for humoral responses were detectable; 3) This form of rejection was steroid and anti-lymphocyte therapy resistant. In the future, suspicion of involvement of humoral component in a rejection episode after ITx should prompt early therapy with plasma exchange and high dose iv globulins.
Published Version
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