Alan D. Betensley

Diagnosis and treatment of antibody mediated rejection in lung transplantation: a retrospective case series.

INTRODUCTION Antibody mediated rejection (AMR) has been identified as an entity that may lead to graft dysfunction. Optimal means for diagnosis and treatment of AMR have not been established. MATERIAL AND METHODS We reviewed the medical records of all patients receiving lung transplantation at Henry Ford Hospital from March 2006 to December 2011. For each patient, we identified potential markers of AMR (immunopathology, histopathology, and serology). Immunopathology was defined as linear c4d immunostaining, histopathology was defined as capillaritis, and serology was defined as identification of donor specific antibody (DSA). We identified all treatment regimens, and we identified clinical and serological outcomes. RESULTS Of 62 patients, 14 were identified with at least one marker of AMR. Only two patients had all three potential markers; immunopathology, histopathology, and serology. Both patients received plasmapheresis (PP) and intravenous immunoglobulin followed by clinical improvement and ultimate elimination of DSA. 4 patients had positive DSA without clinical symptoms, and did not receive treatment with PP, IVIG, or rituximab. DSA has not persisted in these patients, and they remain clinically asymptomatic at up to 803days after identification. DISCUSSION Diagnosis of AMR is difficult due to poorly defined diagnostic markers and confounding factors such as infection. Outcomes are highly variable following treatment that may include therapeutic plasma exchange, intravenous immunoglobulin, and/or rituximab. It is not clear when any or all of these therapies are beneficial. In some cases, symptomatic patients with isolated positive DSA (latent humoral response) can remain asymptomatic and convert to negative DSA without antibody targeted therapy. CONCLUSIONS Firm conclusions are difficult due to the small number of patients and the retrospective nature of the study. Further study is warranted.

Timing of basiliximab induction and development of acute rejection in lung transplant patients

BACKGROUND Acute rejection affects more than 36% of recipients within the first year post-transplantation. The interleukin-2 (IL-2) receptor antagonist basiliximab has been associated with decreased frequency and severity of acute rejection. We investigated whether the timing of induction administration would impact the frequency and severity of acute rejection in the first year after transplantation. METHODS In this study we reviewed 119 patients who underwent lung transplantation at Henry Ford Hospital from October 1994 to January 2009. Prior to January 2000 no patients received induction. From January 2000 to March 2006 the initial dose was given after implantation, and from March 2006 to 2009 basiliximab was given prior to implantation. The primary outcome was cumulative acute rejection score (CAR) in the first post-operative year comparing post- vs pre-implant induction. RESULTS The CAR score for pre-implant basiliximab was 2.5 ± 2.3. This was significantly lower than CAR score of 4.6 ± 3.9 in the post-implant group (p = 0.025). The no-induction group had the highest CAR score at 6.3 ± 3.8 (p = 0.077 compared with the post group). The mean follow-up times in the post and pre group were 5.9 ± 2.3 and 2.3 ± 0.7 years, respectively (p < 0.001). There was no difference in freedom from bronchiolitis obliterans syndrome (BOS), survival or invasive infections between pre- and post-implant induction groups. CONCLUSIONS Basiliximab prior to implant is associated with a lower cumulative acute rejection score over 1 year compared with induction post-implantation. Despite a lower cumulative acute rejection score, there was no significant difference in freedom from BOS or survival.