title: Phenotypic evaluation of B-cell subsets after rituximab for treatment of acute renal allograft rejection in pediatric recipients.
abstract: BACKGROUND
  Recently published pediatric trial of Rituximab for the treatment of CD20+ acute renal allograft rejection (AR) demonstrated transient depletion of circulating/intragraft B cells (Zarkhin et al., Am J Transplant 2008; 8: 2607). In this study, we have evaluated phenotypic definition of circulating B-cell subsets before and after standard of care and B-cell depletional AR therapies.
  
  
  METHODS
  We assessed peripheral B cells by flow cytometry at the time of AR and after AR treatment in 35 pediatric renal transplant recipients: 17 patients with AR who received Rituximab (R-AR; n=11) or steroid pulsing (S-AR; n=6), 18 stable patients with stable graft function with (iSTA; n=10) or without interval infection (hSTA; n=8), and 3 healthy volunteers.
  
  
  RESULTS
  Infections increased memory (P=0.02) and CD19+/CD27⁻/IgD⁻ double negative (DN) B cells (P=0.02) and decreased naive B cells (P=0.01) in iSTA group compared to hSTA patients. Decrease in naive/memory B cells ratio at AR was observed compared with hSTA patients (P=0.01). One year after AR treatment, S-AR patients had persistently lower naive/memory B-cell ratio (P=0.01) and higher DN B cells (P=0.0001) than hSTA patients, whereas after R-AR treatment naive/memory B-cell ratio (P=0.6) and DN B cells (P=0.13) recovered to levels of hSTA patients. R-AR patients with sustained AR resolution (n=8) had trend toward better graft survival (P=0.06) and higher naive B cells (P=0.004) than R-AR relapsers (n=3).
  
  
  CONCLUSIONS
  Increase in circulating memory B cells was seen in pediatric patients at AR. B cells persist as memory after S-AR treatment, whereas Rituximab resulted in repopulation of mostly naive B cells. The heterogeneity in B-cells reconstitution after rejection therapies deserves further investigation as a possible means to follow the clinical and immunologic outcomes of graft rejection.
authors.affiliation: Currently, Stanford University, Palo Alto, CA 94304, USA.
authors.forename: Valeriya
authors.initials: V
authors.lastname: Zarkhin
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Lovelace
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Szu-Chuan
authors.initials: SC
authors.lastname: Hsieh
authors.forename: Minnie M
authors.initials: MM
authors.lastname: Sarwal
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000367:Age Factors; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D053264:B-Cell Activating Factor / Q000097:blood; D053265:B-Cell Activation Factor Receptor / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007156:Immunologic Memory; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D010641:Phenotype; D000069283:Rituximab; D013256:Steroids / Q000627:therapeutic use; D014766:Viremia / Q000209:etiology / Q000276:immunology / Q000628:therapy; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D007166:Immunosuppressive Agents; D013256:Steroids; C435926:TNFRSF13C protein, human; C505719:TNFSF13B protein, human; D000069283:Rituximab