title: Impact of Desensitization on Antiviral Immunity in HLA-Sensitized Kidney Transplant Recipients.
abstract: Viral infections represent significant morbidity and mortality factors in kidney transplant recipients, with CMV, EBV, and BKV infections being most common. Desensitization (DES) with IVIg and rituximab with/without plasma exchange followed by kidney transplantation with alemtuzumab induction increased successful transplant rates in HLA-sensitized patients but may represent an increased risk for viral infections due to severe lymphocyte depletion. Here, we report on the posttransplant viral infection status in 372 DES versus 538 non-DES patients. CMV and EBV viremia were significantly lower in DES patients, while BKV viremia was similar. This trend was observed primarily in CMV sero(-), EBV sero(+), and sero(-) patients. No patient developed PTLD. The incidence of BKAN, allograft, and patient survival was similar in both groups. These viral infections were not associated with subsequent allograft rejection which occurred within 6 months after the infection.Conclusions.The IVIg + rituximab desensitization combined with alemtuzumab induction with triple immunosuppression maintenance does not increase the risk for CMV, EBV, and BKV infections. Possible factors include, in addition to posttransplant antiviral prophylaxis and PCR monitoring, presence of memory T cells and antibodies specific to CMV and likely EBV, NK cell-mediated ADCC despite lymphocyte depletion, elimination of EBV and CMV reservoirs by rituximab and alemtuzumab, and use of IVIg with antiviral properties.
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Mieko
authors.identifier: 0000-0002-5906-1479
authors.initials: M
authors.lastname: Toyoda
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Bong-Ha
authors.initials: BH
authors.lastname: Shin
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Shili
authors.initials: S
authors.lastname: Ge
authors.affiliation: Biostatistics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Mirocha
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Thomas
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Maggie
authors.initials: M
authors.lastname: Chu
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Edgar
authors.initials: E
authors.lastname: Rodriguez
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Chao
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Petrosyan
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Odette A
authors.initials: OA
authors.lastname: Galera
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Vo
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Jua
authors.initials: J
authors.lastname: Choi
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Peng
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kahwaji
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Stanley C
authors.initials: SC
authors.lastname: Jordan
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001739:BK Virus; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D003888:Desensitization, Immunologic; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006680:HLA Antigens / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007668:Kidney / Q000276:immunology; D016030:Kidney Transplantation; D008212:Lymphocyte Depletion; D027601:Polyomavirus Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D000069283:Rituximab / Q000627:therapeutic use; D066027:Transplant Recipients; D014184:Transplantation, Homologous; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control
chemical_list: D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D000069283:Rituximab