Impact of rituximab therapy for treatment of acute humoral rejection.

INTRODUCTION: Antibody mediated rejection (AMR) is associated with a greater incidence of allograft loss because traditional approaches - pulse steroid or anti-lymphocyte antibodies are usually ineffective. This retrospective analysis documented the benefit of rituximab administration in addition to plasmapheresis (PP). METHODS: We retrospectively reviewed the data from 54 kidney transplant patients treated for AMR between 2001 and 2006, including 26 patients who received PP plus rituximab (Group A), versus 28 subjects who underwent PP without rituximab (Group B). Only patients whose serum IgG levels were below normal values received intravenous gamma globulin (IVIG). In addition to clinical and demographic variables we evaluated graft/patient survivals at two years post-diagnosis, Banff classification of rejections, serum creatinine and calculated GFR values at baseline, rejection, resolution as well as three, six, 12 and 24 months thereafter. RESULTS: The demographic features of the cohorts showed no significant differences. The two-year graft survival for patients treated with rituximab plus PP was 90%, significantly better than 60% in the PP cohort (p = 0.005). Upon multivariate analysis administration of rituximab was the most significant factor (>or= 0.009); whereas, IVIG also produced a useful effect (p = 0.05). Neither the mean (>or= 0.42) nor the slope (p = 0.25) of GFR values showed a significant difference among salvaged kidneys over 24 months after completion of AMR treatment. The rates and types of infectious complications at three and six months did not show significant differences or impact on graft survival. CONCLUSION: Addition of rituximab improved the outcomes of PP treatment of antibody mediated rejection episodes.

Hyperhemolytic transfusion reaction attributable to anti-Fy3 in a patient with sickle cell disease.

A case of hyperhemolytic transfusion reaction attributable to anti-Fy3 in a 30-year-oldAfricanAmerican woman with a history of sickle cell disease is reported. The patient was admitted for vaso-occlusive sickle cell crisis and received 4 units of packed RBCs secondary to worsening symptomatic anemia (Hb 5.0 g/dL). On admission, the patient's antibody screen and identification showed anti-V and anti-E, and her antibody history included anti-E,-C,-Jk(b),-N, -V,-S,-Sl(a), and a cold agglutinin with possible anti-I specificity. A DAT performed on her RBCs was negative. RBC units that lacked E, C, Jk(b), N,V, and S were transfused. Posttransfusion Hb was 8.9 g/dL. On day 10 she developed a fever of 103 degrees F, and on day 11 her Hb decreased to 6.4 g/dL. She complained of severe back pain and dark urine. In addition, she became hypertensive, tachycardic, and jaundiced. The DAT indicated the presence of IgG on the patient's RBCs. Anti-Fy3 was identified in the serum and eluate. During the next 24 hours, her Hb decreased to 2.4 g/dL. The LDH level was 1687 U/L, and her reticulocyte count was 2.6%. A delayed hemolytic transfusion reaction with hyperhemolysis secondary to anti-Fy3 was suspected and was successfully treated with IVIG and high-dose prednisone. To the best of our knowledge, this is the first published case of hyperhemolysis in sickle cell disease attributable to anti-Fy3.

Chemokine receptors expressed on T cells in packed red blood cell units change over storage time.

The transfusion of blood products is associated with adverse events that are related to the leukocytes in stored units of blood. These leukocytes have been shown to promote the elaboration of inflammatory cytokines. However, the status of a set of key inflammatory mediators, chemokine receptors, expressed on T lymphocytes in stored red blood cell (RBC) units is largely unknown. We investigated the expression pattern of selected chemokine receptors on T cells from non-leukocyte-reduced RBC units over storage time. Selecting segments from stored RBC units, we evaluated the T-cell subsets for the chemokine receptors CXCR3 and CCR4 by flow cytometry. Statistical analysis was performed by regression analysis. We analysed 30 samples stored between 5 and 38 days. The CD4+ T cells expressing CXCR3 increased by 0.27% daily (P= 0.02), whereas the expression of CCR4 declined by 0.40% daily (P < 0.001). Though the expression of the chemokine receptors on CD8+ cells followed the same trend, the changes were statistically nonsignificant. This study suggests that a longer duration of storage is associated with a higher expression of chemokine receptor CXCR3 and a lower expression of CCR4 on T cells in RBC units, suggesting a pro-inflammatory Th1 bias. The clinical significance of these changes in the setting of adverse transfusion events needs further evaluation.