Immune alterations in subacute sclerosing panencephalitis reflect an incompetent response to eliminate the measles virus.

Semih Ayta,Ozlem Cokar,Gulden Celik Yilmaz,Candan Gurses,Suzan Adin-Cinar,Veysi Demirbilek,Güher Saruhan-Direskeneli,Zuhal Yapici,Safa Baris,Sibel P Yentür,Umit Kuru,Serap Uysal,Emel Onal

doi:10.1371/journal.pone.0245077

Abstract

In subacute sclerosing panencephalitis (SSPE) the persistence of measles virus (MeV) may be related to the altered immune response. In this study, cytokine responses of lymphocytes and monocytes were evaluated in SSPE compared to controls with non-inflammatory (NICON) and inflammatory (ICON) diseases. Patients with SSPE (n = 120), 78 patients with ICON and 63 patients with NICON were included in this study. Phenotypes of peripheral blood mononuclear cells (PBMC) have been analyzed by flow cytometry. CD3 and CD28, and S. aureus Cowan strain I (SAC) stimulated and unstimulated cells were cultured and IL-2, IL-10, IFN-γ, IL-12p40, IL-12p70 and IL-23 were detected in supernatants by ELISA. MeV peptides were used for MeV-specific stimulation and IFN-γ secretion of PBMC was measured by ELISPOT. Spontaneous and stimulated secretions of IL-10 were lower in SSPE compared to both control groups. T cell stimulation induced lower IFN-γ production than ICON group, but higher IL-2 than NICON group in SSPE. Stimulated PBMC produced lower IL-12p70 in SSPE and had decreased CD46 on the cell surface, suggesting the interaction with the virus. IFN-γ responses against MeV peptides were not prominent and similar to NICON patients. The immune response did not reveal an inflammatory activity to eliminate the virus in SSPE patients. Even IL-10 production was diminished implicating that the response is self-limited in controlling the disease.

Highlights

Subacute sclerosing panencephalitis (SSPE) is a progressive disease of the central nervous system (CNS) affecting mainly children and early adolescents
When we evaluated the distributions of T and B cells, and monocytes in the peripheral blood of SSPE patients with two different age-matched control groups with (ICON) or without inflammatory diseases (NICON), the proportion of CD3+ T cells was slightly decreased in SSPE patients compared only to NICON (64.7% vs. 68.9%, p = 0.02), confirming our previous findings [19]
Only IL-10 levels were significantly lower in SSPE compared with both ICON and NICON groups (4.1 vs. 29.8 and 44.5 pg/ml; p = 0.014 and p = 0.002) (Fig 1)

Summary

Introduction

Subacute sclerosing panencephalitis (SSPE) is a progressive disease of the central nervous system (CNS) affecting mainly children and early adolescents. It is a rare and late complication of measles virus (MeV) infection with fatal outcome. In a recent epidemiological study of Istanbul, the incidence was found as 2 per million with a girl dominance [2] Both alterations in the host immune system and changes in the MeV have been the subject of investigations on the pathogenesis of SSPE. Suppression of Th1 cytokine production was reported by demonstrating defective IFN-γ response of peripheral blood mononuclear cells (PBMC) to MeV in SSPE patients with severe disease progression [5]. Activated IL12/IFN-γ and the IL-23/IL-17/IL-22 pathways were reported in SSPE patients [9]

Methods

Results

Discussion

Conclusion