Introduction

Phase III clinical studies have shown that upon Belatacept (CTLA4-Ig) treatment, renal allograft function and anti-HLA immunization are improved compared to anticalcineurin. Here, we analyzed B cell phenotype in a cohort of stable renal transplant recipients treated with Belatacept (Nulojix)

Methods

Twenty three age-matched first kidney transplant patients were included in this study and divided into 3 groups: patients with stable graft function under Belatacept (N=9), or anticalcineurin regimen (N=9), and patients with chronic humoral rejection (N=5). Phenotypic characterization of B cells subpopulations was performed on PBMC and sorted B cells by flow cytometry analysis. Mature and transitional B cell sub-populations were identified by following stainings: CD19/IgD/CD38/CD27 and CD19/CD24/CD38.

We choosed oligonucleotide primers and Taqman Probes for analysis of transcriptional B cells profile using quantitative real-time PCR assay. Gene panel included FCgR2a, FCgR2b, BANK1, BAFF-R, BAFF, APRIL, TACI, BCMA, Il-10 and CD19.

Results

B cell frequency was similar in both Belatacept and anticalcineurin groups (2.8(0.4-12)% vs. 2.2(1.3-6)% (p=0.43)) but was significantly lower in patients with chronic humoral rejection despite no recent increase in immunosuppressive therapy (0.4(0.1-2) (p=0.03 et 0.01)).

Distribution of B cell sub-populations was significantly different between Belatacept and anticalcineurin groups. In Belatacept group, transitional B cell frequency was significantly higher as defined by both phenotypes: CD19+CD24highCD38high (4(0.5-7.3)% vs. 1.25(0-3.7)% (p=0.003)) and CD19+IgDhighCD38highCD27- (4.5(1-7)% vs. 1.1(0.2-4)% (p=0.003)).

Only BAFF-R and BAFF-R/BAFF mRNA levels were significantly lower in Belatacept group than in anticalcineurin group (p=0.01 and 0.003 respectively).

Conclusion

These results show for the first time that Belatacept influences B cell compartment by favoring the occurrence of potentially regulatory transitional B cells. This role may explain the lower allo-immunisation rate observed in Belatacept-treated patients.

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