The B lymphocyte stimulator receptor-ligand system in hepatitis C virus-induced B cell clonal disorders.
OBJECTIVE
The study aim was to examine the B lymphocyte stimulator (BLyS) receptor-ligand system in hepatitis C virus (HCV)-induced B lymphocyte clonal disorders.


METHODS
94 patients with chronic HCV (including 35 with HCV+ mixed cryoglobulinaemia (MC)-vasculitis and nine with HCV+ B cell non-Hodgkin's lymphoma (B-NHL)) and 15 healthy volunteers were included.


RESULTS
A twofold serum BLyS increase was associated with HCV-induced MC-vasculitis, and a threefold increase with HCV-induced B-NHL, compared with patients that were HCV+, but without vasculitis, or healthy controls (p<0.05). Lower membrane BLyS expression in HCV-induced MC-vasculitis was observed. CD19+ BLyS binding and BLyS receptor 3 (BR3) staining showed a stepwise decrease with highest values in healthy controls and who were HCV+ without MC, and lowest in B-NHL (p<0.05, p<0.0001, respectively) with a further decrease in VH1-69+ clonal B cells. BLyS anti-apoptotic effects were maintained despite this decrease in BR3 staining. Complete clinical remission after antiviral treatment was associated with a decrease in serum BLyS, and an increase in BR3 staining. Rituximab treatment was associated with a fivefold increase in serum BLyS (p<0.001), mirroring the depletion of CD19+ cells. BR3 staining in repopulating B cells was significantly decreased (p<0.005).


CONCLUSIONS
The BLyS ligand-receptor activity is increased in HCV-induced B cell clonal disorders, indicating a possible role for treatment targeting the BLyS receptor-ligand system.
Landau
D-A
DA
Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Centre National de la Recherche Sientifique, Universite Pierre et Marrie Curie UMR 7087, Paris, France.
Rosenzwajg
M
M
Saadoun
D
D
Klatzmann
D
D
Cacoub
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000276:immunology; D053264:B-Cell Activating Factor / Q000097:blood*; D053265:B-Cell Activation Factor Receptor / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D003449:Cryoglobulinemia / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D008024:Ligands; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D008875:Middle Aged; D000069283:Rituximab; D014657:Vasculitis / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D055815:Young Adult
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D008024:Ligands; C435926:TNFRSF13C protein, human; D000069283:Rituximab