Maria R Gaiser1, Sonja Textor2, Tilo Senger3, Lysann Schädlich3, Tim Waterboer3, Andreas M Kaufmann4, Caner Süsal5, Michael Pawlita3, Alexander H Enk6, Lutz Gissmann3, Anke S Lonsdorf6. 1. Department of Dermatology, University Hospital of Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany. Electronic address: maria-gaiser@gmx.de. 2. Innate Immunity, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. 3. Department of Genome Modifications and Carcinogenesis, Infection and Cancer Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. 4. Clinic for Gynecology, Charité-Universitaetsmedizin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany. 5. Department of Transplantation Immunology, Institute of Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. 6. Department of Dermatology, University Hospital of Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
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. OBJECTIVES: 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. CONCLUSION: 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.
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. OBJECTIVES: 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. CONCLUSION: 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: Maria Zurek Munk-Madsen; Lars Toft; Tina Kube; Rolf Richter; Lars Ostergaard; Ole S Søgaard; Martin Tolstrup; Andreas M Kaufmann Journal: Hum Vaccin Immunother Date: 2017-12-20 Impact factor: 3.452