title: Evaluation of specific humoral and cellular immune responses against the major capsid L1 protein of cutaneous wart-associated alpha-Papillomaviruses in solid organ transplant recipients.
abstract: BACKGROUND
  Infection with different species of cutaneous human papillomaviruses (cHPV) of genus alpha (cαHPVs) and associated skin disease are highly prevalent in solid organ transplant recipients (OTR), documenting the importance of the immunological control of HPV infection.
  
  
  OBJECTIVE
  To investigate the natural course of cαHPV-specific cellular and humoral immune responses during systemic long-term immunosuppression.
  
  
  METHODS
  Integrating bead-based multiplex serology and flow cytometry we analyzed natural cαHPV-specific antibodies and T(H) cell responses against the major capsid protein L1 of HPV types 2, 27, 57 (species 4) and 3, 10 and 77 (species 2) in sera and blood of OTR before and after initiation of iatrogenic immunosuppression and in comparison to immunocompetent individuals (IC).
  
  
  RESULTS
  Among OTR we observed an overall 42% decrease in humoral L1-specific immune responses during the course of iatrogenic immunosuppression, comparing median values 30 d before and 30 d after initiation of immunosuppressive therapy (p < 0.05). This difference disappeared after long-term (>1 year) immunosuppression. The predominant cellular L1-specific immune response was of type T(H)1 (CD4(+)CD40L(+)IL-2(+)IFN-γ(+)). Consistent with the detected L1-specific antibody titers, L1-specific T(H)1 responses were unchanged in long-term immunosuppressed OTR compared to IC. Notably, cαHPV-L1-specific IL-2(+)/CD40L(+)CD4(+) or IFN-γ(+)/CD40L(+) CD4(+) T(H) cell responses against any of the cαHPV-L1 types were significantly higher in OTR with clinically apparent common warts.
  
  
  CONCLUSIONS
  The systemic humoral immune response against cαHPV may reflect the individual degree of iatrogenic immunosuppression indicating a higher susceptibility for cαHPV infection among OTR during the early phase after organ transplantation. Humoral cαHPV-specific immune responses may show a reconstitution to pre-transplantation levels despite continuous potent immunosuppression.
authors.affiliation: Department of Dermatology, University Hospital of Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany. Electronic address: maria-gaiser@gmx.de.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Gaiser
authors.affiliation: Innate Immunity, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Textor
authors.affiliation: Department of Genome Modifications and Carcinogenesis, Infection and Cancer Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Tilo
authors.initials: T
authors.lastname: Senger
authors.affiliation: Department of Genome Modifications and Carcinogenesis, Infection and Cancer Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Lysann
authors.initials: L
authors.lastname: Schädlich
authors.affiliation: Department of Genome Modifications and Carcinogenesis, Infection and Cancer Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Waterboer
authors.affiliation: Clinic for Gynecology, Charité-Universitaetsmedizin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Kaufmann
authors.affiliation: Department of Transplantation Immunology, Institute of Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
authors.forename: Caner
authors.initials: C
authors.lastname: Süsal
authors.affiliation: Department of Genome Modifications and Carcinogenesis, Infection and Cancer Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.affiliation: Department of Dermatology, University Hospital of Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Enk
authors.affiliation: Department of Genome Modifications and Carcinogenesis, Infection and Cancer Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Gissmann
authors.affiliation: Department of Dermatology, University Hospital of Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
authors.forename: Anke S
authors.initials: AS
authors.lastname: Lonsdorf
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D036022:Capsid Proteins / Q000737:chemistry*; D005260:Female; D005434:Flow Cytometry; D005982:Glutathione Transferase / Q000378:metabolism; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000737:chemistry*; D016377:Organ Transplantation; D027383:Papillomaviridae; D053918:Papillomavirus Vaccines / Q000627:therapeutic use; D010641:Phenotype; D014860:Warts / Q000276:immunology* / Q000821:virology
chemical_list: D036022:Capsid Proteins; C114580:HPV L1 protein, Human papillomavirus; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D007166:Immunosuppressive Agents; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D005982:Glutathione Transferase
keywords: Clinical study; Cutaneous warts; Humoral and cellular immune response; Immunosuppression; Organ transplant recipients; alpha-Papillomaviruses