Peripheral B-Cell Phenotype and BAFF Levels are Associated With HLA Immunization in Patients Awaiting Kidney Transplantation.

BACKGROUND: The role of B-cell subsets in human leukocyte antigen (HLA)-specific humoral responses in patients with end-stage renal disease is poorly documented. The objective of this study was to analyze the potential association between B-cell subsets distribution and anti-HLA antibodies before kidney transplantation. 

METHODS: The authors studied by flow cytometry peripheral B-cell subsets and serum levels of BAFF, the main homeostatic cytokine for peripheral B cells, in 101 consecutive end-stage renal disease patients admitted for transplantation.

RESULTS: In patients with HLA antibodies detected with Luminex single antigen, the proportion of activated naive B cells (Bm2) was significantly higher (64.4±15.1% vs. 52.5±19.1% in HLA antibody-negative patients, P=0.0008) at the expense of memory B cells, as were BAFF serum levels (1,651±1,297 vs. 1,139±693 pg/mL, P<0.0001). Proportion of Bm2 and BAFF levels were positively associated with the diversity of anti-HLA antibodies. In multivariate analysis, besides HLA-immunizing events (pregnancy and previous transplantation), proportion of Bm2 cells but not of other B-cell subsets or BAFF levels was independently associated with the presence and diversity of anti-HLA antibodies. High proportion of Bm2 cells before transplantation was associated with an increased risk of developing de novo donor-specific antibodies during the first year posttransplant. The authors did not find any association between the frequency of antibody-mediated rejection and pretransplant proportion of any B-cell subset or BAFF serum levels.

CONCLUSION: Increased proportions of activated naive B cells are linked with pretransplant HLA immunization and the development of posttransplant donor-specific antibodies (read more)

Risk of Antibody-Mediated Rejection in Kidney Transplant Recipients With Anti-HLA-C Donor-Specific Antibodies

Anti-HLA donor-specific antibodies (DSAs) cause acute and chronic antibody-mediated rejection (AMR). However, the clinical relevance of anti-HLA-C antibodies remains unclear. We evaluated the clinical relevance of the presence of anti-HLA-C DSA at day 0 in renal transplant recipients. In this retrospective, case-controlled study, 608 patients who underwent kidney transplantation between August 2008 and March 2012 were screened for the presence of isolated anti-HLA-C DSA at day 0. A total of 22 renal transplant recipients were selected and followed for a period of 1 year. AMR was classified according to the Banff classification. The 22 patients were compared with 88 immunized patients. Acute AMR was diagnosed in six patients (27.3%). The median level of DSA at day 0 was 1179 (530–17 941). The mean fluorescence intensity in the anti-C group was 4966 (978–17 941) in the AMR group and 981 (530–8012) in the group of patients without AMR. Acute AMR was diagnosed less frequently in the 88 immunized individuals (9.1%) than in the DSA anti-C group (p = 0.033). The level of DSA at day 0 was predictive for AMR (p = 0.017). Patients with a high level of pretransplant anti-HLA-C DSAs are likely to develop acute AMR during the first year after transplantation (read more)

Influenza Vaccination and Humoral Alloimmunity in Solid Organ Transplant Recipients

Annual influenza vaccination is recommended in solid organ transplant (SOT) recipients. However, concerns have been raised about the impact of vaccination on anti-graft alloimmunity. We evaluated the humoral alloimmune responses to influenza vaccination in a cohort of SOT recipients between October 2008 and December 2011. Anti-HLA antibodies were measured before and 4-8 weeks after influenza vaccination using a solid phase assay. Overall, 169 SOT recipients were included (kidney=136, lung=26, liver=3, combined=4). Five (2.9%) of 169 patients developed de novo anti-HLA antibodies after vaccination, including one patient who developed donor-specific antibodies (DSA) eight months after vaccination. In patients with pre-existing anti-HLA antibodies, median MFI was not significantly different before and after vaccination (p=0.73 for class I and p=0.20 for class II anti-HLA antibodies) and no development of de novoDSA was observed. Five episodes of rejection (2.9%) were observed within 12 months after vaccination and only one patient had de novo anti-HLA antibodies. The incidence of development of anti-HLA antibodies after influenza vaccination in our cohort of SOT recipients was very low. Our findings indicate that influenza vaccination is safe and does not trigger humoral alloimmune responses in SOT recipients (read more)