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 difficult to identify, remainin...

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Main Authors: Leyla Mohammad, Mathias Fousse, Gentiana Wenzel, Marina Flotats Bastardas, Klaus Faßbender, Ulrich Dillmann, Bernhard Schick, Michael Zemlin, Barbara C. Gärtner, Urban Sester, David Schub, Tina Schmidt, Martina Sester
Format: Article
Language:English
Published: BMC 2023-10-01
Series:Journal of Neuroinflammation
Subjects:
Online Access:https://doi.org/10.1186/s12974-023-02933-4
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author Leyla Mohammad
Mathias Fousse
Gentiana Wenzel
Marina Flotats Bastardas
Klaus Faßbender
Ulrich Dillmann
Bernhard Schick
Michael Zemlin
Barbara C. Gärtner
Urban Sester
David Schub
Tina Schmidt
Martina Sester
author_facet Leyla Mohammad
Mathias Fousse
Gentiana Wenzel
Marina Flotats Bastardas
Klaus Faßbender
Ulrich Dillmann
Bernhard Schick
Michael Zemlin
Barbara C. Gärtner
Urban Sester
David Schub
Tina Schmidt
Martina Sester
author_sort Leyla Mohammad
collection DOAJ
description 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 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 may also help to identify the causative pathogen in PFPs of unknown origin. Methods In this observational study, pathogen-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, as well as markers for differentiation (CD27) and proliferation (Ki67). Pathogen-specific 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 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 of borrelia-specific 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-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. If confirmed in larger studies, antigen-specific immune-phenotyping may have the potential to improve specificity of the clinical diagnosis.
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spelling doaj.art-4127a58eb95248769cc0765e32e1c5882023-11-26T13:51:56ZengBMCJournal of Neuroinflammation1742-20942023-10-0120111210.1186/s12974-023-02933-4Alterations in pathogen-specific cellular and humoral immunity associated with acute peripheral facial palsy of infectious originLeyla Mohammad0Mathias Fousse1Gentiana Wenzel2Marina Flotats Bastardas3Klaus Faßbender4Ulrich Dillmann5Bernhard Schick6Michael Zemlin7Barbara C. Gärtner8Urban Sester9David Schub10Tina Schmidt11Martina Sester12Department of Transplant and Infection Immunology, Saarland UniversityDepartment of Neurology, Saarland UniversityDepartment of Otorhinolaryngology, Saarland UniversityDepartment of Pediatrics and Neonatology, Saarland UniversityDepartment of Neurology, Saarland UniversityDepartment of Neurology, Saarland UniversityDepartment of Otorhinolaryngology, Saarland UniversityDepartment of Pediatrics and Neonatology, Saarland UniversityDepartment of Medical Microbiology and Hygiene, Saarland UniversitySHG Klinikum VölkingenDepartment of Transplant and Infection Immunology, Saarland UniversityDepartment of Transplant and Infection Immunology, Saarland UniversityDepartment of Transplant and Infection Immunology, Saarland UniversityAbstract 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 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 may also help to identify the causative pathogen in PFPs of unknown origin. Methods In this observational study, pathogen-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, as well as markers for differentiation (CD27) and proliferation (Ki67). Pathogen-specific 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 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 of borrelia-specific 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-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. If confirmed in larger studies, antigen-specific immune-phenotyping may have the potential to improve specificity of the clinical diagnosis.https://doi.org/10.1186/s12974-023-02933-4Peripheral facial palsyT cellsCellular immunityVZVHSVBorrelia
spellingShingle Leyla Mohammad
Mathias Fousse
Gentiana Wenzel
Marina Flotats Bastardas
Klaus Faßbender
Ulrich Dillmann
Bernhard Schick
Michael Zemlin
Barbara C. Gärtner
Urban Sester
David Schub
Tina Schmidt
Martina Sester
Alterations in pathogen-specific cellular and humoral immunity associated with acute peripheral facial palsy of infectious origin
Journal of Neuroinflammation
Peripheral facial palsy
T cells
Cellular immunity
VZV
HSV
Borrelia
title Alterations in pathogen-specific cellular and humoral immunity associated with acute peripheral facial palsy of infectious origin
title_full Alterations in pathogen-specific cellular and humoral immunity associated with acute peripheral facial palsy of infectious origin
title_fullStr Alterations in pathogen-specific cellular and humoral immunity associated with acute peripheral facial palsy of infectious origin
title_full_unstemmed Alterations in pathogen-specific cellular and humoral immunity associated with acute peripheral facial palsy of infectious origin
title_short Alterations in pathogen-specific cellular and humoral immunity associated with acute peripheral facial palsy of infectious origin
title_sort alterations in pathogen specific cellular and humoral immunity associated with acute peripheral facial palsy of infectious origin
topic Peripheral facial palsy
T cells
Cellular immunity
VZV
HSV
Borrelia
url https://doi.org/10.1186/s12974-023-02933-4
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