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

• We analyzed HPV-specific immune responses in organ transplant recipients.
• Main cellular immune response against any HPV type was of TH1 type.
• Immune responses were higher in patients with common warts.
• Immune responses reflect individual level of iatrogenic immunosuppression.

BackgroundInfection 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.ObjectivesTo investigate the natural course of cαHPV-specific cellular and humoral immune responses during systemic long-term immunosuppression.MethodsIntegrating bead-based multiplex serology and flow cytometry we analyzed natural cαHPV-specific antibodies and TH 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).ResultsAmong OTR we observed an overall 42% decrease in humoral L1-specific immune responses during the course of iatrogenic immunosuppression, comparing median values 30d before and 30d 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 TH1 (CD4+CD40L+IL-2+IFN-γ+). Consistent with the detected L1-specific antibody titers, L1-specific TH1 responses were unchanged in long-term immunosuppressed OTR compared to IC. Notably, cαHPV-L1-specific IL-2+/CD40L+CD4+ or IFN-γ+/CD40L+ CD4+ TH cell responses against any of the cαHPV-L1 types were significantly higher in OTR with clinically apparent common warts.ConclusionThe 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.