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Abstract: FR-PO746

Serum B-Cell Activating Factor Levels Are an Early Predictor of the Response to Rituximab in Patients with Idiopathic Nephrotic Syndrome

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

Authors

  • Colucci, Manuela, Bambino Gesù Children's Hospital - IRCCS, Rome, Italy
  • Emma, Francesco, Bambino Gesù Children's Hospital - IRCCS, Rome, Italy
  • Vivarelli, Marina, Bambino Gesù Children's Hospital - IRCCS, Rome, Italy
Background

Treatment with rituximab (RTX), a B-cell depleting anti-CD20 antibody, has a prolonged efficacy in preventing relapses in pediatric idiopathic nephrotic syndrome (INS). Length of remission following RTX correlates with length of B cell, especially memory B cell, depletion. However, some patients experience early recurrence of INS following RTX treatment. Serological predictors of response to RTX are as yet unidentified.

Methods

Levels of serum B cell-activating factor (BAFF) and of B cell subsets were serially monitored by ELISA and flow cytometry respectively in 14 steroid-dependent INS children treated with RTX up to recurrence of NS. An initial dose of RTX (375 mg/m2), repeated at 7 days in case of incomplete depletion of B cells, was administered.

Results

Three patients relapsed after 6.1±0.2 months (R) whilst the other 11 never relapsed during this period (NR). At baseline there was no significant difference between these two groups. One month after RTX treatment, all B cell subpopulations were completely depleted, and total CD19+ B cells started to reappear at 6 months in both groups, with no significant difference in the number of total B cells between R and NR. However, serum BAFF levels and the B cell subset repopulation were different in the two groups. In the NR group, serum BAFF levels significantly rose at 1 month and remained increased during the follow-up, sustaining the significant re-emergence of transitional and mature B cells (p<0.05 vs 1 months). Unexpectedly, serum BAFF levels never increased in the R group, and this was reflected by the reduced recovery of transitional and mature B cells. In contrast, R patients showed a significantly increased reconstitution of memory and in particular switched memory B cells at 6 months compared to the NR group in whom the memory B cells remained depleted (p<0.05 compared with R at 6 months).

Conclusion

Total B cell recovery is not a good predictor of relapse in INS pediatric patients treated with rituximab, as this population is composed of several B cell subsets with different functions and different reconstitution patterns following RTX treatment. On the contrary, serum BAFF levels post-RTX treatment and the re-emergence of memory and in particular of switched memory B cells may better predict the response to RTX in pediatric INS patients.

Funding

  • Private Foundation Support