Immunologic parameters and viral infections in patients desensitized with intravenous immunoglobulin and rituximab.
Desensitization with IVIG and rituximab followed by transplantation with alemtuzumab or daclizumab induction is an effective clinical protocol. Here, we examined the effects of this protocol on immune cell number, T cell function by Cylex ImmuKnow®, CMV-specific CD8+ T cell (CMV-Tc) activity, total and viral-specific immunoglobulin levels and viral infections. In 17 highly HLA-sensitized (HS) patients who received desensitization, CD19+ cells were undetectable immediately after desensitization, while other immune cells were unchanged. No alteration in Cylex or CMV-Tc levels was seen. In separate 14 HS patients who were desensitized followed by transplantation, T cell numbers were near zero after alemtuzumab, while NK cell reduction was minimal. Early B cell recovery was not a risk for antibody-mediated rejection. Total IgG, IgM, and IgA remained in the normal range up to 12.6 months post-transplant, and CMV IgG level did not change. CMV-Tc activity was eliminated post-transplant in some patients, but recovered by 4 months post-transplant. None of them developed CMV infection. In conclusion, IVIG-rituximab-desensitization does not significantly alter T cell function pre-transplant, or reduce Ig levels below the normal range post-transplant. Although post-transplant induction therapy is associated with a transient depletion of viral-specific CD8+ memory cells, it does not increase risks for viral infections.
Transplant Immunology Laboratory, Comprehensive Transplant Center, Cedars-Sinai Medical Center/UCLA School of Medicine, 8700 Beverly Blvd., SSB111, Los Angeles, CA 90048, USA. shili.ge@cshs.org
Shili
S
Ge
Andy
A
Pao
Ashley
A
Vo
Nathan
N
Deer
Artur
A
Karasyov
Anna
A
Petrosyan
Joseph
J
Kahwaji
Marina
M
Lukovsky
Ning-Ning
NN
Chai
Angela
A
Aguiluz
James
J
Mirocha
Stanley C
SC
Jordan
Mieko
M
Toyoda
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000276:immunology; D000077561:Daclizumab; D003888:Desensitization, Immunologic / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use; D007136:Immunoglobulins / Q000097:blood; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D015166:Monitoring, Immunologic; D000069283:Rituximab; D013601:T-Lymphocytes / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D007074:Immunoglobulin G; D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D000074323:Alemtuzumab; D000069283:Rituximab; D000077561:Daclizumab