CLINICAL AND EPIDEMIOLOGICAL RESEARCH

The B lymphocyte stimulator receptor–ligand system in hepatitis C virus-induced B cell clonal disorders

D-A Landau¹, M Rosenzwajg¹, D Saadoun^1,2, D Klatzmann¹, P Cacoub^1,2

¹ Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Centre National de la Recherche Sientifique, Universite Pierre et Marrie Curie UMR 7087, Paris, France
² Service de Médecine Interne, Hôpital Pitié-Salpêtrière, Paris, France

Professeur Patrice Cacoub, Service de Médecine Interne, Groupe Hospitalier La Pitié-Salpêtrière, 47–83, Boulevard de l’Hôpital, 75013 Paris, France; patrice.cacoub{at}psl.aphp.fr

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 V_H1-69+ 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.

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