Peripheral B-cell phenotype and BAFF levels are associated with HLA immunization in patients awaiting kidney transplantation.
BACKGROUND
The role of B-cell subsets in human leukocyte antigen (HLA)-specific humoral responses in patients with end-stage renal disease is poorly documented. The objective of this study was to analyze the potential association between B-cell subsets distribution and anti-HLA antibodies before kidney transplantation.


METHODS
The authors studied by flow cytometry peripheral B-cell subsets and serum levels of BAFF, the main homeostatic cytokine for peripheral B cells, in 101 consecutive end-stage renal disease patients admitted for transplantation.


RESULTS
In patients with HLA antibodies detected with Luminex single antigen, the proportion of activated naive B cells (Bm2) was significantly higher (64.4 ± 15.1% vs. 52.5 ± 19.1% in HLA antibody-negative patients, P=0.0008) at the expense of memory B cells, as were BAFF serum levels (1,651 ± 1,297 vs. 1,139 ± 693 pg/mL, P<0.0001). Proportion of Bm2 and BAFF levels were positively associated with the diversity of anti-HLA antibodies. In multivariate analysis, besides HLA-immunizing events (pregnancy and previous transplantation), proportion of Bm2 cells but not of other B-cell subsets or BAFF levels was independently associated with the presence and diversity of anti-HLA antibodies. High proportion of Bm2 cells before transplantation was associated with an increased risk of developing de novo donor-specific antibodies during the first year posttransplant. The authors did not find any association between the frequency of antibody-mediated rejection and pretransplant proportion of any B-cell subset or BAFF serum levels.


CONCLUSIONS
Increased proportions of activated naive B cells are linked with pretransplant HLA immunization and the development of posttransplant donor-specific antibodies.
1 INSERM U1013, Hôpital Necker-Enfants Malades, Paris, France. 2 Université Paris Descartes, Sorbonne Paris Cite, Paris, France. 3 Service de Transplantation Rénale Adulte, Hôpital Necker-Enfants Malades, Assistance Publique-Hopitaux de Paris, Paris, France. 4 Department of Immunohaematology, Leiden University Medical Center, Leiden, the Netherlands. 5 Service de Biostatistique et d'Informatique Médicale, Hôpital Necker, Assistance Publique-Hopitaux de Paris, Paris, France. 6 Address correspondence to: Lucienne Chatenoud, M.D., Ph.D., or Sophie Candon, M.D., Ph.D., INSERM U1013, Hôpital Necker-Enfants Malades, 149, rue de Sèvres, 75015 Paris, France.
Renaud
R
Snanoudj
Sophie
S
Candon
Dave L
DL
Roelen
Jean-Philippe
JP
Jais
Frans H
FH
Claas
Christophe
C
Legendre
Lucienne
L
Chatenoud
D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology; D053264:B-Cell Activating Factor / Q000097:blood*; D016175:B-Lymphocyte Subsets / Q000166:cytology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007165:Immunosuppression Therapy; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000628:therapy*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D012306:Risk; D055815:Young Adult
D000906:Antibodies; D053264:B-Cell Activating Factor; D016207:Cytokines; D006680:HLA Antigens; C505719:TNFSF13B protein, human