title: Reduced varicella-zoster-virus (VZV)-specific lymphocytes and IgG antibody avidity in solid organ transplant recipients.
abstract: BACKGROUND
  Varicella-zoster-virus (VZV) infection may cause significant morbidity and mortality in immunocompromised patients. So far, only IgG-anti-VZV antibody concentrations were used to estimate immunity against VZV, but the antibody binding strength (avidity) together with VZV-specific cellular responses have not been evaluated in solid organ transplant (SOT) recipients.
  
  
  METHODS
  Thus, we assessed the humoral and cellular immune responses to two doses of the VZV vaccine (vacc) and wild-type VZV infection (wt) in 23 kidney (KTx) and 19 liver transplant (LTx) recipients including children and adults compared to 48 healthy controls (HC) for measurement of IgG-anti-VZV relative avidity index (RAI) and frequency of VZV-specific peripheral blood mononuclear cells (PBMCs) in vaccinated individuals using an adapted ELISA and IFN-gamma ELISPOT, respectively.
  
  
  RESULTS
  KTx(wt) (median RAI 72.3%) or LTx(wt) (79.2%) and KTx(vacc) (91.0%) or LTx(vacc) (72.5%) showed lower avidities compared to HC(wt) (84.5%) and HC(vacc) (94.0%), respectively, despite equally distributed IgG-anti-VZV concentrations. RAI>60% (high avidity) was detected in all HC, but only in 69.0% of SOT patients. KTx(vacc) (median 64 spot forming units SFU/500,000 PBMCs) and LTx(vacc) (67 SFU) had significantly lower VZV-specific cellular responses compared to HC(vacc) (268 SFU).
  
  
  CONCLUSIONS
  The diminished cellular reactivity to VZV has to be considered in SOT patients receiving immunosuppressive treatments when evaluating immunity against VZV. IgG antibody avidity and VZV-specific cellular responses may serve as additional markers to evaluate immunity against VZV in SOT recipients. The role of wild-type exposures and endogenous VZV re-activation on long-term immunity in SOT patients has to be awaited to establish recommendations for vaccine spacing in these patients, considering immunogenicity and safety aspects.
authors.affiliation: Department of Pediatrics, Innsbruck Medical University, Innsbruck, Austria. Prelog_M@kinderklinik.uni-wuerzburg.de
authors.forename: Martina
authors.initials: M
authors.lastname: Prelog
authors.forename: Jörn
authors.initials: J
authors.lastname: Schönlaub
authors.forename: Verena
authors.initials: V
authors.lastname: Jeller
authors.forename: Giovanni
authors.initials: G
authors.lastname: Almanzar
authors.forename: Kerstin
authors.initials: K
authors.lastname: Höfner
authors.forename: Saskia
authors.initials: S
authors.lastname: Gruber
authors.forename: Thomas
authors.initials: T
authors.lastname: Eiwegger
authors.forename: Reinhard
authors.initials: R
authors.lastname: Würzner
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000915:Antibody Affinity / Q000276:immunology*; D002644:Chickenpox / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006562:Herpes Zoster / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D016867:Immunocompromised Host / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008297:Male; D014181:Transplantation Immunology; D019737:Transplants / Q000276:immunology*; D014611:Vaccination; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G