Humoral and cellular immunity to varicella-zoster virus in patients with autoimmune diseases.

Rondaan, C. (Christien) (2013) Humoral and cellular immunity to varicella-zoster virus in patients with autoimmune diseases. thesis, Medicine.

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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 3-20-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 38 patients with SLE, 33 patients with GPA and 51 healthy controls (HC). In all individuals, serum antibody levels to VZV-glycoprotein (gp) was measured by a validated in-house gpELISA As control antibodies to Diphtheria were measured in all participants. Cellular responses to VZV were by IFN-γ ELIspot assay and CFSE-dye dilution proliferation assay using cryo-preserved PBMCs and UV-inactivated VZV as antigen. Results: Antibodies to VZV were significantly (P=0.0004) increased in SLE patients (median 132 IU/ml, range 21-1095) compared to HC (median 66 IU/ml, range 7-634). Values in GPA patients (median 75 IU/ml, range 2-1154) were not statistically different from values in HC. In contrast, antibodies against Diphtheria in both SLE and GPA patients were significantly (P=0.012 and P=0.037) decreased compared to HC. SLE patients had a significantly lower number of IFN-γ spot forming cells against VZV (P=0.033). In GPA patients no difference was found. Furthermore, the proliferation index (PI) of CD4+ T-lymphocytes was significantly (P=0.034) 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. The results suggest that increased prevalence of VZV in 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.

Item Type:	Thesis (Thesis)
Supervisor name:	Westra, Dr. Johanna
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:43
Last Modified:	25 Jun 2020 10:43
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/489

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