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T Cells Show an Immune Response Against Epstein-Barr Virus Nuclear Antigen 1 (EBNA-1) in Paediatric Autoimmune
Jytte Hendrikse1, Aafke M de Ligt1,2, Roos A W Wennink1
1Department of Ophthalmology, University Medical Centre Utrecht, University Utrecht, Utrecht, The Netherlands.
Insights
Most pediatric uveitis patients show T cell reactivity to Epstein-Barr virus EBNA-1 antigen, irrespective of HLA-DRB1*15:01 status. A specific epitope response was noted in one HLA-DRB1*15:01 positive patient.
Area of Science:
- Immunology
- Ophthalmology
- Virology
Background:
- Paediatric uveitis is an inflammatory eye condition.
- Epstein-Barr virus (EBV) is a common human herpesvirus.
- The EBV EBNA-1 antigen and its epitopes are implicated in immune responses.
Purpose of the Study:
- To investigate T cell reactivity in children with uveitis against the EBV EBNA-1 antigen and a specific epitope.
- To correlate T cell responses with the HLA-DRB1*15:01 genetic profile.
Main Methods:
- ELISPOT assay was used to measure IFN-γ T cell responses.
- Patients were tested against a pool of EBV EBNA-1 antigen and a specific EBNA-1 epitope.
- HLA-DRB1*15:01 status was determined using next-generation sequencing or TaqMan assay.
Main Results:
- 81.8% of paediatric uveitis patients exhibited a T cell response to the complete EBV EBNA-1 antigen.
- No significant difference in T cell response was observed between HLA-DRB1*15:01 positive and negative uveitis patients.
- One patient with intermediate uveitis, homozygous for HLA-DRB1*15:01, showed a T cell response to the EBNA-1 AA 397-408 epitope.
Conclusions:
- The majority of paediatric uveitis patients have a measurable T cell response to the complete EBV EBNA-1 antigen.
- This response appears independent of the HLA-DRB1*15:01 genetic background in this cohort.
- A specific T cell response to the EBNA-1 AA 397-408 epitope was observed in a single HLA-DRB1*15:01 positive patient.
Purpose:
The purpose of this study was to examine the reactivity of T cells from children with paediatric uveitis to the complete Epstein-Barr virus (EBV) EBNA-1 antigen and to the EBNA-1 AA 397-408 epitope in relation to the class II HLA-DRB1*15:01 genetic profile.
Methods:
We used ELISPOT to measure the IFN-γ T cell response of eleven patients with paediatric non-infectious uveitis and three control patients to a peptide pool containing the complete EBV EBNA-1 antigen and to the EBV EBNA-1 AA 397-408 peptide motif. Next-generation sequencing data or, when unavailable, TaqMan assay was used to categorize patients based on HLA-DRB1*15:01 profile.
Result:
Overall, 9/11 (81.8%) of uveitis patients had a positive T cell response against the EBV EBNA-1 pool. Of the five HLA-DRB1*15:01 positive uveitis and control patients, four (80%) had a positive T cell response to the EBV EBNA-1 pool. No statistically significant differences were seen in number of spot forming units per 106 cells against the EBV EBNA-1 pool between HLA-DRB1*15:01 positive compared to HLA-DRB1*15:01 negative uveitis patients. One patient with intermediate uveitis who was homozygous positive for HLA-DRB1*15:01 had a positive T cell response to the EBNA-1 AA 397-408 peptide motif condition.
Conclusion:
In this exploratory study, we found that the majority of uveitis patients, regardless of HLA-DRB1*15:01 genetic background, had a measurable T cell response against the complete EBV EBNA-1 antigen. A positive T cell response against the EBNA-1 AA 397-408 epitope specifically was measured in one uveitis patient; a homozygote HLA-DRB1*15:01 positive patient with intermediate uveitis.
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