Concurrent Cellular Rejection Research Articles

Cellular Involvement Rather Than Humoral Characteristics Predict Renal Graft Dysfunction 1 Year After Antibody Mediated Rejection.

Antibody-mediated rejection (AMR) after renal transplantation is frequently resistant to conventional anti-rejection therapy and often results in graft dysfunction (Gdys); however, risk factors for Gdys following AMR remain poorly defined. The purpose of this study was to identify predictors of Gdys, defined as graft loss or GFR reduction by ≥50%, at 1 year post-AMR treatment. Kidney transplant recipients treated for biopsy-proven AMR (n=49) were reviewed. Factors approaching significance (p<0.2) in the univariate analysis were included in a multivariate logistic regression backward elimination model to identify independent risk factors for Gdys. Mean time to AMR diagnosis following transplant was 14.5 months. Gdys at 1 year was seen in 22 (45%) patients, with graft loss occurring in 9 patients. Baseline characteristics including age, gender, race, donor type, sensitization, and induction type were similar between groups. The most common anti-humoral therapies administered were IVIG (n=46) and plasma exchange (n=39), with rituximab (n=22) or bortezomib (n=8) given in certain cases; ATG was added to anti-humoral therapies for mixed antibody-cellular rejections. Factors associated with Gdys by univariate analysis were prior cellular rejection, mixed rejection, and plasma cell infiltrates, while bortezomib use was associated with function at 1 year. In contrast, Gdys was not associated with DSA presence, number of antibody specificities, DSA strength, presence of capillaritis or glomerulitis, or other anti-humoral treatments. Multivariate analysis revealed mixed rejection as the only independent predictor of Gdys. Our data suggests that in renal transplantation, concurrent cellular rejection, rather than humoral characteristics, predicts poor graft outcomes at 1 year.Table: No Caption available.Table: No Caption available.

Cardiovascular Mortality Among Heart Transplant Recipients With Asymptomatic Antibody-Mediated or Stable Mixed Cellular and Antibody-Mediated Rejection

Little has been reported on the clinical significance of asymptomatic antibody-mediated rejection (AMR) alone or mixed rejection (MR), defined as concurrent cellular rejection (CR) and AMR in heart transplantation. In this study, we examined whether a differential impact on cardiovascular mortality (CVM) existed when comparing asymptomatic AMR, to stable MR or CR. The Utah Transplantation Affiliated Hospitals (UTAH) Cardiac Transplant Program pathology database of all heart transplant recipients between 1985 and 2004 was queried. Patients were classified as cellular, antibody-mediated, or mixed rejectors based on their predominant pattern of rejection type in the first three months post-transplant. Kaplan-Meier survival curves were fit to each of the three groups and analyses were adjusted for age at the time of transplant, gender, and underlying primary cardiac disease. Eight hundred and sixty nine heart transplant recipients qualified for analysis. Over the study period, patients with asymptomatic AMR or stable MR patterns had significantly worse CVM when compared to patients with stable CR pattern (AMR, 21.2%; MR, 18.0%; CR, 12.6%; AMR vs. CR, p = 0.009; MR vs. CR, p = 0.001). In contrast, CVM was comparable in patients with asymptomatic AMR or stable MR patterns (p = 0.9). Asymptomatic or subclinical AMR and MR are clinically relevant, should be recognized, and deserve consideration for therapeutic intervention in hopes of avoiding adverse outcomes.

Humoral rejection in cardiac transplantation: risk factors, hemodynamic consequences and relationship to transplant coronary artery disease

Background Acute cellular rejection is the mechanism of most immune-related injury in cardiac transplant recipients. However, antibody-mediated humoral rejection (HR) has also been implicated as an important clinical entity following orthotopic heart transplantation. Humoral rejection has been reported to play a role in graft dysfunction in the early post-transplant period, and to be a risk factor for the development of transplant coronary artery disease. Some involved in transplantation pathology doubt the existence of clinically significant humoral rejection in cardiac allografts. Those who recognize its existence disagree on its possible role in graft dysfunction or graft coronary artery disease. In this study, we report clinical features of patients with the pathologic diagnosis of HR at our institution since July 1997, when we began systematic surveillance for humoral rejection. Methods We reviewed medical records of patients with the pathologic diagnosis of HR without concurrent cellular rejection between July 1997 and January 2001. Diagnosis was based on routine histology (“swollen cells” distending capillaries, interstitial edema and hemorrhage) and immunofluorescence (capillary deposition of immunoglobulin and complement with HLA-DR positivity), or immunoperoxidase staining of paraffin-embedded tissue (numerous CD68-positive macrophages and fewer swollen endothelial cells distending capillaries). Results A total of 44 patients (4 to 74 years old) showed evidence of HR without concurrent cellular rejection at autopsy or on one or more biopsies. Although females comprised only 26% of our transplant population, 23 patients (52%) with HR were female. A positive peri-operative flow cytometry T-cell crossmatch was observed in 32% of HR patients compared with 12% of controls ( p = 0.02). Hemodynamic compromise consisting of shock, hypotension, decreased cardiac output/index and/or a rise in capillary wedge or pulmonary artery pressure was observed in 47% of patients at the time of diagnosis of HR. Six patients (5 females) died (14% mortality) with evidence of HR at or just before autopsy, 6 days to 16 months after transplantation. The incidence of transplant coronary artery disease was 10% greater at 1 year, and 36% greater at 5 years, in patients with HR when compared with non-HR patients. Conclusion Humoral rejection was associated with acute hemodynamic compromise in 47% of patients, and was the direct cause of death in 6 patients (13%). Humoral rejection is a clinicopathologic entity with a high incidence in women and is associated with acute hemodynamic compromise, accelerated transplant coronary artery disease and death.