Journal
TRANSPLANTATION
Volume 84, Issue 7, Pages 842-850Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.tp.0000282786.58754.2b
Keywords
CXCL13; BCA-1; chemokine; transplantation; SLC
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Background. Intrarenal B cell clusters are associated with poor clinical outcome in acute interstitial rejection. The incidence of B cell aggregates in vascular rejection and the effect of therapy with the monoclonal CD20 antibody rituximab on intrarenal B cells are currently unclear. Methods. We analyzed the incidence of B cell clusters in patients with vascular rejection by immunohistochemistry and compared the influence of rituximab treatment plus conventional therapy with that of conventional immunosuppression alone on intrarenal B cells. Furthermore intrarenal expression of the B cell attracting chemokine BCA-1/CXCL13 and the lymphoid chemokine SLC/CCL21 were analyzed. Results. Nine of 16 patients with vascular rejection displayed intrarenal B cell clusters strictly co-localizing with expression of the B cell attractant chemokine BCA-1/CXCL13. Addition of rituximab to conventional treatment lead to complete depletion of intrarenal B cells (98.3 +/- 136.4 CD20, 90.7 +/- 113.2 CD19 vs. 0 +/- 0 CD20, 0 +/- 0 CD19 B cells/hpf, P < 0.001). Creatinine decreased from 5.0 +/- 4.1 to 1.9 +/- 0.4 mg/dl at discharge, and to 1.9 +/- 0.5 mg/dl after three months (P < 0.02). No effect on intrarenal B cells was observed in the patients not treated with rituximab (72.8 +/- 73.0 vs. 80.3 +/- 75.3 CD20, 75.6 +/- 86.6 vs. 85.7 +/- 82.0 CD19). At discharge, creatinine had improved in this group from 5.1 +/- 4.1 mg/dl to 1.8 +/- 0.5 mg/dl and to 1.7 +/- 0.6 mg/dl after 3 months (P < 0.05). Conclusion. In summary, our study reports two main findings, namely the previously unrecognized high prevalence of intrarenal B cell clusters in 56% of biopsies with acute vascular rejection and a complete depletion of intrarenal B cells by addition of Rituximab to conventional treatment.
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