Rituximab removes intrarenal B cell clusters in patients with renal vascular allograft rejection.
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).


CONCLUSIONS
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.
Steinmetz
Oliver M
OM
Medizinische Klinik, Universitätsklinikum Hamburg Eppendorf, Hamburg, Germany. o.steinmetz@uke.uni-hamburg.de
Lange-Hüsken
Felix
F
Turner
Jan-Eric
JE
Vernauer
Almut
A
Helmchen
Udo
U
Stahl
Rolf A K
RA
Thaiss
Friedrich
F
Panzer
Ulf
U
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19 / Q000096:biosynthesis; D018951:Antigens, CD20 / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000378:metabolism*; D054382:Chemokine CXCL13 / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012082:Renal Veins / Q000378:metabolism; D000069283:Rituximab; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D018951:Antigens, CD20; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069283:Rituximab