Alterations in pathogen-specific cellular and humoral immunity associated with acute peripheral facial palsy of infectious origin

Abstract

AbstractBackground and ObjectivesPeripheral facial palsy (PFP) is a common neurologic symptom which can be triggered by pathogens or autoimmunity as well as trauma, tumors, cholesteatoma and further local conditions disturbing the peripheral section of the nerve. In general, its cause is often difficult to identify, remaining unknown in over two thirds of cases. As we have previously shown that the quantity and quality of pathogen-specific T cells change during active infections, we hypothesized that such changes also may help to identify the causative pathogen in PFPs of unknown origin.MethodsPathogen-specific T cells were quantified in blood samples of 55 patients with PFP and 23 healthy controls after stimulation with antigens from varicella-zoster virus (VZV), herpes-simplex viruses (HSV) or borrelia. T cells were further characterized by expression of the inhibitory surface molecule CTLA-4, and markers for differentiation (CD27) and proliferation (Ki67). Pathogen-specific antibody responses were analyzed using ELISA. Results were compared with conventional diagnostics.ResultsPatients with PFP were more often HSV-seropositive than controls (p=0.0003), whereas VZV-and borrelia-specific antibodies did not differ between groups. Although the quantity and general phenotypical characteristics of antigen-specific T cells did not differ either, expression of CTLA-4 and Ki67 was highly increased in VZV-specific T cells of 9 PFP patients, of which 5 showed typical signs of cutaneous zoster. In the remaining 4 patients, a causal relationship with VZV was possible but remained unclear by clinical standard diagnostics. A similar CTLA-4- and Ki67-expression profile was also found in a patient with acute neuroborreliosis.DiscussionIn conclusion, the high prevalence of HSV-seropositivity among PFP-patients may indicate an underestimation of HSV-involvement in PFP, even though HSV-specific T-cell characteristics seem insufficient to identify HSV as a causative agent. In contrast, striking alterations in VZV- and borrelia-specific T-cell phenotype and function may allow identification of VZV- and borrelia-triggered PFPs thus bearing the potential to improve specificity of the clinical diagnosis.