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

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Abstract

Background

B-cells are increasingly recognized as important players in alloimmunity. B cell-activating factor (BAFF) and its receptor BAFF-R are essential for B-cell differentiation and survival. Data on BAFF levels in pediatric renal transplant (RT) patients are scarce.

Objective

It is known from adult data that elevated BAFF levels correlate with an unfavorable outcome in bone marrow and kidney recipients. To analyze this hypothesis in pediatric renal transplant patients we performed a cross-sectional analysis of serum BAFF levels, lymphocyte surface BAFF-R expression, and clinical variables in a cohort of 43 pediatric renal transplant patients.

Methods

We studied serum BAFF, CD19+ B-, and FoxP3+ regulatory T-cells (Tregs) and BAFF-R expression in 43 children 2.9 (0.1–12.4) years after RT on maintenance immunosuppression. Twenty-two healthy children and 19 children with chronic kidney disease stage 5 (CKD5) served as controls.

Results

BAFF levels were significantly higher in RT patients than in healthy children (1,435±574 vs 894±189 pg/mL; p<0.0001) whereas numbers of B-cells and Tregs were significantly lower. BAFF-R expression on B-cells was decreased after RT (531±334 vs 707±257 MFI; p<0.005), BAFF inversely correlated with BAFF-R (r=-0.5022, p<0.006), but not with B-cell count. BAFF was elevated in CKD5 patients (1,276±294 pg/mL). In RT patients BAFF was significantly higher in those with eGFR <60 ml/min/1.73m2 (1,553±447 vs 1,234±323 pg/mL; p=0.02). BAFF levels and BAFF-R expression did not correlate with HLA antibody status, time after transplantation, age or gender of the patients.

Conclusion

Serum BAFF concentrations were significantly elevated in pediatric RT patients. They correlated with decreased BAFF-R expression on CD19+ B-cells and impaired allograft function. Our findings of a dysregulated BAFF/BAFF-R axis may be of clinical relevance after renal transplantation and therefore underline the importance of further research into BAFF-dependent mechanisms.

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Acknowledgement

This work was supported in part by a grant from the charity organization “Hamburg macht Kinder gesund.”

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Authors and Affiliations

  1. University Medical Center Hamburg-Eppendorf, Pediatric Nephrology, Martinistrasse 52, 20246, Hamburg, Germany

    Anja Lehnhardt, Franziska Dunst, Michael van Husen, Sebastian Loos, Jun Oh & Markus J. Kemper

  2. University Medical Center Hamburg-Eppendorf, Hepatobiliary and Transplant Surgery, Hamburg, Germany

    Anja Lehnhardt & Martina Koch

  3. University Medical Center Hamburg-Eppendorf, Transfusion Medicine, Hamburg, Germany

    Thomas Eiermann

Authors
  1. Anja Lehnhardt
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  2. Franziska Dunst
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Correspondence to Anja Lehnhardt.

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Lehnhardt, A., Dunst, F., van Husen, M. et al. Elevated serum levels of B-cell activating factor in pediatric renal transplant patients. Pediatr Nephrol 27, 1389–1395 (2012). https://doi.org/10.1007/s00467-012-2142-8

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  • DOI: https://doi.org/10.1007/s00467-012-2142-8

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