Hepatitis B immunoglobulins inhibit dendritic cells and T cells and protect against acute rejection after liver transplantation.
The efficacy of anti-viral intravenous immunogobulins (anti-HBs Ig and anti-CMV Ig) in preventing acute rejection after liver transplantation was assessed in a retrospective analysis, and correlated to their effects on immune cells in vitro. HBs Ag-positive liver graft recipients (n = 40) treated prophylactically with anti-HBs Ig had a significantly lower incidence of acute rejection compared with recipients without viral hepatitis (n = 147) (12% vs. 34%; p = 0.012), while the incidence of rejection in HCV-positive recipients (n = 29) was similar to that in the control group. Treatment with anti-CMV Ig (n = 18) did not protect against rejection. In vitro, anti-HBs Ig suppressed functional maturation of and cytokine production by human blood-derived dendritic cells (DC) at concentrations similar to the serum concentrations reached during anti-HBs Ig treatment of liver graft recipients. In addition, anti-HBs Ig inhibited allo-antigen- and lectin-stimulated proliferation of peripheral T cells. Anti-CMV Ig suppressed functional DC-maturation and alloantigen-stimulated T-cell proliferation, but not lectin-driven T-cell proliferation. In conclusion, anti-HBs Ig protects against acute rejection after liver transplantation, probably by functional inhibition of the two principal immune cells involved in allograft rejection, DC and T cells.
Kwekkeboom
J
J
Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center, Rotterdam, The Netherlands. j.kwekkeboom@erasmusmc.nl
Tha-In
T
T
Tra
W M W
WM
Hop
W
W
Boor
P P C
PP
Mancham
S
S
Zondervan
P E
PE
Vossen
A C T M
AC
Kusters
J G
JG
de Man
R A
RA
Metselaar
H J
HJ
D000328:Adult; D049109:Cell Proliferation; D003587:Cytomegalovirus / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006509:Hepatitis B / Q000276:immunology*; D006510:Hepatitis B Antibodies / Q000737:chemistry; D006514:Hepatitis B Surface Antigens / Q000737:chemistry; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D007136:Immunoglobulins / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology* / Q000627:therapeutic use; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007511:Ischemia; D007519:Isoantigens / Q000737:chemistry; D037102:Lectins / Q000737:chemistry; D016031:Liver Transplantation / Q000276:immunology* / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D007519:Isoantigens; D037102:Lectins; C045781:cytomegalovirus-specific hyperimmune globulin; C045213:hepatitis B hyperimmune globulin