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THU0306 Cellular and Humoral Responses to Varicella-Zoster Virus in Patients with Autoimmune Diseases
  1. C. Rondaan1,
  2. A. de Haan2,
  3. G. Horst1,
  4. J. C. Hempel1,
  5. C. van Leer3,
  6. N. A. Bos1,
  7. S. van Assen4,
  8. M. Bijl5,
  9. J. Westra1
  1. 1Rheumatology and Clinical Immunology
  2. 2Medical Microbiology, Division of Molecular Virology
  3. 3Medical Microbiology, Division of Clinical Virology
  4. 4Internal Medicine, Division of Infectious Diseases, University Medical Center Groningen
  5. 5Internal Medicine and Rheumatology, Martini Hospital, Groningen, Netherlands

Abstract

Background Herpes zoster (HZ) results from reactivation of varicella-zoster virus (VZV). Besides the symptoms of HZ, 8-27% of patients with herpes zoster develop postherpetic neuralgia (PHN), leading to debilitating pains. In particular elderly, HIV-patients and patients using immunosuppressive drugs are at increased risk for developing HZ and PHN. Patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and granulomatosis with polyangiitis (GPA) have a 5 to 16-fold increased risk compared to the general population. Use of immunosuppressive drugs is associated with the development of HZ in these patients.

Objectives Aim of the study was to evaluate if the susceptibility of patients with autoimmune disease is due to decreased levels of cellular and/or humoral responses to VZV in these patients.

Methods A cross-sectional study on VZV-specific immunity was performed in 78 patients with SLE, 71 patients with GPA and 65 age- and sex-matched healthy controls (HC). In all individuals, serum antibody levels to VZV-glycoprotein (Gp) was measured by an in-house ELISA and, in a large proportion of tested individuals, compared to responses measured by VIDAS and Serion VZV-Gp ELISA. As control antibodies to Diphtheria (IBL-International) were measured in all participants. Cellular responses to VZV were measured in a large proportion of patients and controls by IFN-γ ELIspot assay and CFSE-dye dilution proliferation assay using cryopreserved PBMCs and UV-inactivated VZV as antigen.

Results There was a strong correlation between the values measured with the in-house anti-Gp-VZV ELISA and VIDAS, and Serion anti-Gp-VZV ELISA (all p<0.0001). Antibodies to VZV were significantly (P=0.0005) increased in SLE patients (median 2019 mIU/ml, range 210 - ≥10000) compared to HC (median 1110 mIU/ml, range 110 - 8224). Values in GPA patients (median 1495 mIU/ml, range 20 - ≥10000) were not statistically different from values in HC. In contrast, antibodies against Diphtheria in both SLE and GPA patients were significantly (P<0.001) decreased compared to HC. Moreover, SLE and GPA patients had a significantly lower number of IFN-γ spot forming cells against VZV (P<0.05). Furthermore, the proliferation index (PI) of CD4+ T-lymphocytes was significantly (P<0,05) decreased in SLE patients compared to HC, but not in GPA patients.

Conclusions Patients with SLE have increased antibody levels against VZV compared to levels detected in HC, which cannot be explained by polyclonal hypergammaglobulinaemia as antibodies to Diphtheria were decreased in comparison to HC. Cellular immunity however, was decreased in these patients as well as in GPA patients. Our results suggest that increased prevalence of VZV in SLE and GPA patients is due to a poor cellular response to VZV. Vaccination strategies should not be based upon humoral immunity and should aim to boost cellular immunity against VZV.

Disclosure of Interest None Declared

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