Remodeling of B-Cell Subsets in Blood during Pegylated IFNα-2a Therapy in Patients with Chronic Hepatitis B Infection.
The ultimate goal of pegylated interferon-alfa-2a (Peg-IFN-α) therapy in chronic hepatitis B (CHB) infection is HBsAg seroconversion. Even though B cells are major mediators of a positive clinical outcome, their modulation during Peg-IFN-α therapy has not yet been described. We investigated here the effects of Peg-IFN-α on eight circulating B-cell subsets thanks to an original multi-gating approach based on CD19, CD27, IgD, CD10, and CD38 markers in patients with CHB treated with nucleos(t)ide analog alone or in combination with Peg-IFN-α. These dynamic changes were analyzed during the 48-weeks of Peg-IFN-α therapy and up to 2 years after the cessation of treatment. The CD19+CD27-IgD+CD10+CD38high transitional B cells and the CD19+CD27+IgD-CD10-CD38high plasmablasts continuously increased, whereas the CD19+CD27-IgD+CD10-CD38low naive, CD19+CD27+IgD+ natural memory, and CD19+CD27+IgD-CD10-CD38low post-germinal center B cells decreased during the course of Peg-IFNα treatment. Such modulations correlated with a sustained increase in sCD30 levels and the decrease in plasma HBsAg. However, no seroconversion occurred and all parameters returned to baseline after the stop of the treatment. Peg-IFN-α therapy mediates a remodeling of B-cell compartmentalization, without clinical relevance. Our study provides new insights into the immunomodulatory effects of Peg-IFN-α on circulating B-cells, and questioned the benefit of the add-on Peg-IFN-α treatment in CHB.
University Joseph Fourier, Grenoble, F-38041, France; INSERM, U823, Immunobiology & Immunotherapy of Cancers, La Tronche, F-38706, France.|EFS Rhone-Alpes, R&D Laboratory, La Tronche, F-38701, France.
Caroline
C
Aspord
University Joseph Fourier, Grenoble, F-38041, France; INSERM, U823, Immunobiology & Immunotherapy of Cancers, La Tronche, F-38706, France.|CHU Grenoble, Michallon Hospital, Hepato-gastroenterology unit, Grenoble, F-38043, France.
Juliana
J
Bruder Costa
University Joseph Fourier, Grenoble, F-38041, France; INSERM, U823, CRI/Institut Albert Bonniot, Grenoble, F-38000, France; Department of Immunology, CHU de Grenoble, Grenoble, F-38000, France.
Marie-Christine
MC
Jacob
CHU Grenoble, Michallon Hospital, Hepato-gastroenterology unit, Grenoble, F-38043, France.|University Joseph Fourier, Grenoble, F-38041, France; INSERM, U823, Analytic Immunology of chronic pathologies, La Tronche, F-38706, France.
Tania
T
Dufeu-Duchesne
ANRS (France REcherche Nord & sud Sida-hiv Hépatites: FRENSH), Paris, France.
Inga
I
Bertucci
Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), 75012, Paris, France.
Noelle
N
Pouget
Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), 75012, Paris, France.
Ophelie
O
Brevot-Lutton
INSERM U1052-CNRS 5286, Cancer Research Center of Lyon (CRCL), Lyon, France.|Hepatology Department, Hospices Civils de Lyon, Lyon, France.|Université de Lyon, Lyon, France.
Fabien
F
Zoulim
Hepato-gastroenterology department, Hospital Saint Joseph, Marseille, 13008, France.
Marc
M
Bourliere
University Joseph Fourier, Grenoble, F-38041, France; INSERM, U823, Immunobiology & Immunotherapy of Cancers, La Tronche, F-38706, France.|EFS Rhone-Alpes, R&D Laboratory, La Tronche, F-38701, France.
Joel
J
Plumas
CHU Grenoble, Michallon Hospital, Hepato-gastroenterology unit, Grenoble, F-38043, France.|University Joseph Fourier, Grenoble, F-38041, France; INSERM, U823, Analytic Immunology of chronic pathologies, La Tronche, F-38706, France.
Vincent
V
Leroy
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000187:drug effects / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a