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

Abstract

Background Peripheral facial palsy (PFP) is a common neurologic symptom which can be triggered by pathogens, autoimmunity, trauma, tumors, cholesteatoma or further local conditions disturbing the peripheral section of the nerve. In general, its cause is often difcult to identify, remaining unknown in over two thirds of cases. As we have previously shown that the quantity and quality of pathogen-specifc T cells change during active infections, we hypothesized that such changes may also help to identify the causative pathogen in PFPs of unknown origin. Methods In this observational study, pathogen-specifc T cells were quantifed 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, as well as markers for diferentiation (CD27) and proliferation (Ki67). Pathogen-specifc antibody responses were analyzed using ELISA. Results were compared with conventional diagnostics. Results Patients with PFP were more often HSV-seropositive than controls (p=0.0003), whereas VZV- and borreliaspecifc antibodies did not difer between groups. Although the quantity and general phenotypical characteristics of antigen-specifc T cells did not difer either, expression of CTLA-4 and Ki67 was highly increased in VZV-specifc 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 profle of borrelia-specifc T cells was also found in a patient with acute neuroborreliosis. Discussion In conclusion, the high prevalence of HSV-seropositivity among PFP-patients may indicate an underestimation of HSV-involvement in PFP, even though HSV-specifc T cell characteristics seem insufcient to identify HSV as a causative agent. In contrast, striking alterations in VZV- and borrelia-specifc T cell phenotype and function may allow identifcation of VZV- and borrelia-triggered PFPs. If confrmed in larger studies, antigen-specifc immune-phenotyping may have the potential to improve specifcity of the clinical diagnosis.