Treatment of Antibody-Mediated Rejection After Kidney Transplantation: Immunological Effects, Clinical Response, and Histological Findings.

BACKGROUND Antibody-mediated rejection (AMR) presents with diverse clinical manifestations and can have a potential negative impact on graft function and survival. If not treated successfully, AMR can lead to 20-30% graft loss after 1 year. Little is known about the efficacy of AMR treatment, and the most appropriate therapeutic strategy has not yet been determined. This study evaluated the effects of AMR treatment with plasmapheresis (PP) and intravenous immunoglobulin (IVIG) on renal function, intensity of anti-HLA antibodies, and graft biopsy morphology. MATERIAL AND METHODS This single-center retrospective cohort study included renal transplant recipients with biopsy-proven AMR who were treated with PP and/or IVIG. Clinical findings, mean fluorescence intensity of donor-specific anti-HLA antibodies (DSA), and graft histology findings, classified according to Banff score at the time of AMR and 6 and 12 months later, were evaluated. RESULTS Of the 42 patients who met the inclusion criteria, 38 (90.5%) received IVIG and 26 (61.9%) underwent PP. At AMR diagnosis, 36 (85.7%) patients had proteinuria, with their estimated glomerular filtration rate remaining stable during follow-up. During the first year, 8 (19.0%) patients experienced graft failure, but none died with a functioning graft. Reductions in the class I panel of reactive antibodies were observed 6 and 12 months after AMR treatment, with significant reductions in DSA-A and -B fluorescence intensity, but no changes in DSA-DQ. Graft biopsy showed reductions in inflammation and C4d scores, without improvements in microvascular inflammation. CONCLUSIONS AMR treatment reduced biopsy-associated and serological markers of AMR, but did not affect DSA-DQ.

Effect of Preformed or De Novo Anti-HLA Antibodies on Function and Graft Survival in Kidney Transplant Recipients.

BACKGROUND Donor-specific antibodies (DSA), directed against human leucocyte antigens (HLA), are associated with increased risk for graft rejection in kidney transplantation. Anti-HLA antibodies detection by Luminex™ present high sensitivity and accuracy, but its interpretation after transplantation is not completely clear. The aim of this study was to evaluate the impact of anti-HLA antibodies, preformed or de novo, on renal function, graft survival, and incidence of antibody-mediated acute rejection (AMR). MATERIAL AND METHODS A retrospective cohort of 86 kidney transplant recipients was divided into 3 groups according to the presence of anti-HLA antibodies before transplantation: donor-specific antibodies (DSA+, n=15), non-DSA (non-DSA, n=39), and negative pre-transplant panel reactive antibodies (PRA) that became positive after transplantation (PRA-, n=22). Forty-nine recipients with negative PRA pre- and post-transplantation were excluded. Antibody specificity and intensity of fluorescence (MFI) and their relationship with renal function, proteinuria, AMR, and graft failure were evaluated. RESULTS Among patients who completed 1 year of follow-up, there was no significant difference in serum creatinine, estimated glomerular filtration rate, or proteinuria. AMR incidence was 9.5% in the DSA group, 2.3% in the non-DSA group, and 9.1% in the PRA- group. There was no correlation between fluorescence intensity and/or antibodies class (I or II) with increased risk of AMR. Thirteen grafts failed within 1 year post-transplant, there were 9 deaths due to infection, and only 1 due to AMR (PRA- group, DSA de novo at 3 months). CONCLUSIONS In contrast to previous reports, we did not find a correlation between incidence of AMR and MFI intensity in this series.

Platelet antibody detection by flow cytometry: an effective method to evaluate and give transfusional support in platelet refractoriness.

BACKGROUND: Immune platelet refractoriness is mainly caused by human leukocyte antigen antibodies (80-90% of cases) and, to a lesser extent, by human platelet antigen antibodies. Refractoriness can be diagnosed by laboratory tests and patients should receive compatible platelet transfusions. A fast, effective and low cost antibody-screening method which detects platelet human leukocyte/platelet antigen antibodies is essential in the management of immune platelet refractoriness. OBJECTIVE: The aim of this study was to evaluate the efficiency of the flow cytometry platelet immunofluorescence test to screen for immune platelet refractoriness. METHODS: A group of prospective hematologic patients with clinically suspected platelet refractoriness treated in a referral center in Campinas, SP during July 2006 and July 2011 was enrolled in this study. Platelet antibodies were screened using the flow cytometry platelet immunofluorescence test. Anti-human leukocyte antigen antibodies were detected by commercially available methods. The sensitivity, specificity and predictive values of the immunofluorescence test were determined taking into account that the majority of antiplatelet antibodies presented human leukocyte antigen specificity. RESULTS: Seventy-six samples from 32 female and 38 male patients with a median age of 43.5 years (range: 5-84 years) were analyzed. The sensitivity of the test was 86.11% and specificity 75.00% with a positive predictive value of 75.61% and a negative predictive value of 85.71%. The accuracy of the method was 80.26%. CONCLUSION: This study shows that the flow cytometry platelet immunofluorescence test has a high correlation with the anti-human leukocyte antigen antibodies. Despite a few limitations, the method seems to be efficient, fast and feasible as the initial screening for platelet antibody detection and a useful tool to crossmatch platelets for the transfusional support of patients with immune platelet refractoriness.

Platelet antibody detection by flow cytometry: an effective method to evaluate and give transfusional support in platelet refractoriness

BACKGROUND:Immune platelet refractoriness is mainly caused by human leukocyte antigen antibodies (80-90% of cases) and, to a lesser extent, by human platelet antigen antibodies. Refractoriness can be diagnosed by laboratory tests and patients should receive compatible platelet transfusions. A fast, effective and low cost antibody-screening method which detects platelet human leukocyte/platelet antigen antibodies is essential in the management of immune platelet refractoriness. OBJECTIVE: The aim of this study was to evaluate the efficiency of the flow cytometry platelet immunofluorescence test to screen for immune platelet refractoriness. METHODS: A group of prospective hematologic patients with clinically suspected platelet refractoriness treated in a referral center in Campinas, SP during July 2006 and July 2011 was enrolled in this study. Platelet antibodies were screened using the flow cytometry platelet immunofluorescence test. Anti-human leukocyte antigen antibodies were detected by commercially available methods. The sensitivity, specificity and predictive values of the immunofluorescence test were determined taking into account that the majority of antiplatelet antibodies presented human leukocyte antigen specificity. RESULTS: Seventy-six samples from 32 female and 38 male patients with a median age of 43.5 years (range: 5-84 years) were analyzed. The sensitivity of the test was 86.11% and specificity 75.00% with a positive predictive value of 75.61% ...