Elevated serum levels of B-cell activating factor in pediatric renal transplant patients

Lehnhardt, Anja; Dunst, Franziska; Husen, Michael van; Loos, Sebastian; Oh, Jun; Eiermann, Thomas; Koch, Martina; Kemper, Markus J.

doi:10.1007/s00467-012-2142-8

Cited by 13 publications

(9 citation statements)

References 32 publications

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“…We add to this aspect by reporting significantly lower BAFF‐R expression on those B cells, which had returned 1 yr after rituximab treatment. This finding is in accordance with previously published data and seems to occur through a post‐transcriptional mechanism as a consequence of chronic increase in sBAFF . We observed remarkably high BAFF‐R expression with MFI >1500 in three of our ABOc patients.…”

Section: Discussionsupporting

confidence: 93%

“…One‐yr flow cytometry data were available in 11/12 ABOi and 16/18 ABOc patients. Sample preparation was performed as previously described . In short, peripheral venous blood samples were taken before rituximab treatment, directly before transplantation and any other immunosuppressive treatment (IS) and at 1, 12, and 52 wk of post‐transplantation.…”

Section: Methodsmentioning

confidence: 99%

“…BAFF not only promotes survival and selection of autoreactive B cells but also allows emergence of alloreactive clones producing according antibodies . There is evidence that elevated serum (s) BAFF levels negatively affect long‐term renal allograft function .…”

mentioning

confidence: 99%

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High B‐cell activating factor is not associated with worse 3‐year graft outcome in blood group‐incompatible kidney transplantation with rituximab induction

Lehnhardt

Strecker

Eiermann

et al. 2015

Clinical Transplantation

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B cells and their regulation by B-cell activating factor BAFF are of growing interest in kidney transplantation (KTx). There is evidence that high serum (s) BAFF leads to increased allosensitization and impaired long-term graft function. We prospectively investigated sBAFF, peripheral blood lymphocytes (PBL), and donor-specific HLA antibodies (DSA) in patients after ABOi with B-cell depleting rituximab induction treatment and compared them to a group of blood group-compatible (ABOc) living donor kidney recipients. Twelve patients after ABOi and 18 after ABOc were included. After rituximab treatment prior to ABOi, B cells remained significantly lower 1 year after KTx (1.2% (0.0-17.8) compared to ABOc of 8.6% (2.8-35.0), p = 0.0004, and also BAFF-R expression was significantly lower in ABOi (p < 0.006). sBAFF remained elevated 1 year post-Tx compared to ABOc (3615 ± 1800 vs. 1394 ± 493 pg/mL, p < 0.004). Kidney function was not significantly different between both groups after 1, 2, and 3 years. The use of rituximab in ABOi together with maintenance immunosuppression leads to significant elevation of sBAFF and lowering of B-cell numbers for more than 1 year, and this does not correlate with worse 3-year graft outcome.

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Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

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High B‐cell activating factor is not associated with worse 3‐year graft outcome in blood group‐incompatible kidney transplantation with rituximab induction

Lehnhardt

Strecker

Eiermann

et al. 2015

Clinical Transplantation

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“…In the present study, sBAFF and membrane‐bound BAFF were all elevated, but chip assays showed a decreasing mRNA level of BAFF in positive recipients. These expression characteristics of BAFF were distinct from previous reports and need to be further explored.…”

Section: Discussioncontrasting

confidence: 71%

B‐cell‐activating factor code and human cytomegalovirus infection in renal transplant recipients

Dong

et al. 2014

Microbiology and Immunology

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The objective of the present study was to explore the correlation between the BAFF signal and HCMV-TLR activation in RTx recipients complicated by HCMV. Peripheral blood (anticoagulated by EDTA-Na 2 ) and urine of 113 RTx recipients were collected; healthy volunteers were controlled. Urine HCMV-DNA was detected by real-time PCR. Recipients were classified into a positive group (>10,000 copies/mL urine) and a negative group (<10,000 copies/mL urine). ELISA results showed that sBAFF, sera anti-HCMV pp65 immunoglobulin (Ig)G antibody, and total IgG all significantly increased in recipients with positive HCMV-DNA (>10,000 copies/mL urine) (P < 0.05) compared with negative recipients (<10,000 copies/mL urine). In the positive group, HCMV-DNA copies and total IgG positively correlated with sBAFF (r ¼ 0.988 and 0.625, respectively) (P < 0.05). Luminex assay results suggested that the incidence of anti-HLA I and II and MICA antibody obviously increased in positive recipients. The expression level of BAFF and BAFF-R increased in positive recipients. A total of 88 particular genes-involved in TLR signaling pathways, NF-kB signaling pathways, and cytokinecytokine receptor signaling pathways-were detected in real-time PCR chip assay. A total of 46 genes were differentially expressed greater than two-fold, and the expression characteristic of BAFF-R was concordant with FACS results. Our findings are that activation of HCMV would induce or enhance the activation of BAFF code in RTx recipients, which may independently or cooperatively participate in renal allograft injury and decrease the long-term outcome of renal allografts.

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“…B‐lymphocyte counts in the peripheral blood were monitored by flow cytometry on a FACS Canto (BD Bioscience, San Jose, California, USA) using monoclonal antibodies against CD19 and CD20 (4G7 and L27, both BD Bioscience) as previously described .…”

Section: Patient and Methodsmentioning

confidence: 99%

Four-year allograft survival in a highly sensitized combined liver-kidney transplant patient despite unsuccessful anti-HLA antibody reduction with rituximab, splenectomy, and bortezomib

et al. 2013

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SummaryAlthough donor-specific lymphocytotoxic antibodies are regarded as a contraindication for kidney transplantation (KTx), the data available for liver or combined liver or kidney transplantation (cLKTx) are scarce. Here, we report a case of a highly sensitized young man receiving his sixth liver and second kidney graft. Multiple anti-HLA antibodies were present at the time of transplantation. As a result of suspected antibody-mediated graft damage, the patient was treated with rituximab, plasmapheresis, intravenous immunoglobulins, splenectomy, and bortezomib to decrease the antibody production. So far, patient and allograft survival has reached 4 years despite failure to achieve a permanent reduction of anti-HLA antibodies, and particularly nondonor directed antibodies.

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Elevated serum levels of B-cell activating factor in pediatric renal transplant patients

Cited by 13 publications

References 32 publications

High B‐cell activating factor is not associated with worse 3‐year graft outcome in blood group‐incompatible kidney transplantation with rituximab induction

High B‐cell activating factor is not associated with worse 3‐year graft outcome in blood group‐incompatible kidney transplantation with rituximab induction

B‐cell‐activating factor code and human cytomegalovirus infection in renal transplant recipients

Four-year allograft survival in a highly sensitized combined liver-kidney transplant patient despite unsuccessful anti-HLA antibody reduction with rituximab, splenectomy, and bortezomib

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