Paediatric autoimmune uveitis is associated with intraocular antibodies against Epstein–Barr virus Nuclear Antigen 1 (EBNA-1). Hendrikse, J., Bont, L. J., Schellekens, P. A., De Groot-Mijnes, J. D., De Boer, J. H., & Kuiper, J. J. eBioMedicine, 115:105681, May, 2025. ![Paediatric autoimmune uveitis is associated with intraocular antibodies against Epstein–Barr virus Nuclear Antigen 1 (EBNA-1) [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex **Background** Non-infectious uveitis is an immune-mediated disease characterized by vision-threatening inflammation within the eye. Increasing evidence indicates that microbial agents promote non-infectious uveitis, but the natural history of immune responses to pathogens in patients remains unexplored. We determined intraocular antibodies against pathogens in paediatric uveitis. **Methods** We used peptide microarrays containing 3760 linear B-cell epitopes from 196 human pathogens to profile IgG levels in eye fluid biopsies and paired serum samples from 18 Dutch paediatric patients and 6 age-matched controls. We compared intensities of single epitopes and clusters based on overlapping amino acid sequence of peptides. Next-generation sequencing data was obtained to determine the HLA-DRB1∗15:01 genotype. **Findings** Intraocular antibody profiles largely matched serum profiles and were characterized by high IgG against the conserved PALTAVET-motif of enterovirus family members, as well as broad epitope reactivity against Epstein–Barr virus (EBV). The aqueous humour of patients showed elevated levels of antibodies against peptides containing the RRPFFHPV-motif of Epstein–Barr Virus Nuclear Antigen 1 [EBNA-1]. Antibody levels against the RRPFFHPV-motif of EBNA1 were significantly higher in individuals that carry the HLA-DRB1∗15:01 risk allele of paediatric uveitis. **Interpretation** Intraocular antibodies against an immunogenic epitope of EBV showed an association with paediatric uveitis, particularly HLA-DRB1∗15:01 positive uveitis, indicating a potential link between EBV-specific immune responses and autoimmune uveitis. **Funding** Funding for this research was received from Fischer Stichting (UZ2022-3), ODAS (2021-02), LSBS and ANVVB.
@article{hendrikse_paediatric_2025,
title = {Paediatric autoimmune uveitis is associated with intraocular antibodies against {Epstein}–{Barr} virus {Nuclear} {Antigen} 1 ({EBNA}-1)},
volume = {115},
issn = {23523964},
url = {https://linkinghub.elsevier.com/retrieve/pii/S2352396425001252},
doi = {10.1016/j.ebiom.2025.105681},
abstract = {**Background**
Non-infectious uveitis is an immune-mediated disease characterized by vision-threatening inflammation within the eye. Increasing evidence indicates that microbial agents promote non-infectious uveitis, but the natural history of immune responses to pathogens in patients remains unexplored. We determined intraocular antibodies against pathogens in paediatric uveitis.
**Methods**
We used peptide microarrays containing 3760 linear B-cell epitopes from 196 human pathogens to profile IgG levels in eye fluid biopsies and paired serum samples from 18 Dutch paediatric patients and 6 age-matched controls. We compared intensities of single epitopes and clusters based on overlapping amino acid sequence of peptides. Next-generation sequencing data was obtained to determine the HLA-DRB1∗15:01 genotype.
**Findings**
Intraocular antibody profiles largely matched serum profiles and were characterized by high IgG against the conserved PALTAVET-motif of enterovirus family members, as well as broad epitope reactivity against Epstein–Barr virus (EBV). The aqueous humour of patients showed elevated levels of antibodies against peptides containing the RRPFFHPV-motif of Epstein–Barr Virus Nuclear Antigen 1 [EBNA-1]. Antibody levels against the RRPFFHPV-motif of EBNA1 were significantly higher in individuals that carry the HLA-DRB1∗15:01 risk allele of paediatric uveitis.
**Interpretation**
Intraocular antibodies against an immunogenic epitope of EBV showed an association with paediatric uveitis, particularly HLA-DRB1∗15:01 positive uveitis, indicating a potential link between EBV-specific immune responses and autoimmune uveitis.
**Funding**
Funding for this research was received from Fischer Stichting (UZ2022-3), ODAS (2021-02), LSBS and ANVVB.},
language = {en},
urldate = {2025-04-18},
journal = {eBioMedicine},
author = {Hendrikse, Jytte and Bont, Louis J. and Schellekens, Peter A.W.J.F. and De Groot-Mijnes, Jolanda D.F. and De Boer, Joke H. and Kuiper, Jonas J.W.},
month = may,
year = {2025},
keywords = {Application - Autoimmune Research, PEPperCHIP - Standard, PEPperCHIP Infectious Disease Epitope Micorarray},
pages = {105681},
}
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We determined intraocular antibodies against pathogens in paediatric uveitis. **Methods** We used peptide microarrays containing 3760 linear B-cell epitopes from 196 human pathogens to profile IgG levels in eye fluid biopsies and paired serum samples from 18 Dutch paediatric patients and 6 age-matched controls. We compared intensities of single epitopes and clusters based on overlapping amino acid sequence of peptides. Next-generation sequencing data was obtained to determine the HLA-DRB1∗15:01 genotype. **Findings** Intraocular antibody profiles largely matched serum profiles and were characterized by high IgG against the conserved PALTAVET-motif of enterovirus family members, as well as broad epitope reactivity against Epstein–Barr virus (EBV). The aqueous humour of patients showed elevated levels of antibodies against peptides containing the RRPFFHPV-motif of Epstein–Barr Virus Nuclear Antigen 1 [EBNA-1]. Antibody levels against the RRPFFHPV-motif of EBNA1 were significantly higher in individuals that carry the HLA-DRB1∗15:01 risk allele of paediatric uveitis. **Interpretation** Intraocular antibodies against an immunogenic epitope of EBV showed an association with paediatric uveitis, particularly HLA-DRB1∗15:01 positive uveitis, indicating a potential link between EBV-specific immune responses and autoimmune uveitis. **Funding** Funding for this research was received from Fischer Stichting (UZ2022-3), ODAS (2021-02), LSBS and ANVVB.","language":"en","urldate":"2025-04-18","journal":"eBioMedicine","author":[{"propositions":[],"lastnames":["Hendrikse"],"firstnames":["Jytte"],"suffixes":[]},{"propositions":[],"lastnames":["Bont"],"firstnames":["Louis","J."],"suffixes":[]},{"propositions":[],"lastnames":["Schellekens"],"firstnames":["Peter","A.W.J.F."],"suffixes":[]},{"propositions":[],"lastnames":["De","Groot-Mijnes"],"firstnames":["Jolanda","D.F."],"suffixes":[]},{"propositions":[],"lastnames":["De","Boer"],"firstnames":["Joke","H."],"suffixes":[]},{"propositions":[],"lastnames":["Kuiper"],"firstnames":["Jonas","J.W."],"suffixes":[]}],"month":"May","year":"2025","keywords":"Application - Autoimmune Research, PEPperCHIP - Standard, PEPperCHIP Infectious Disease Epitope Micorarray","pages":"105681","bibtex":"@article{hendrikse_paediatric_2025,\n\ttitle = {Paediatric autoimmune uveitis is associated with intraocular antibodies against {Epstein}–{Barr} virus {Nuclear} {Antigen} 1 ({EBNA}-1)},\n\tvolume = {115},\n\tissn = {23523964},\n\turl = {https://linkinghub.elsevier.com/retrieve/pii/S2352396425001252},\n\tdoi = {10.1016/j.ebiom.2025.105681},\n\tabstract = {**Background**\nNon-infectious uveitis is an immune-mediated disease characterized by vision-threatening inflammation within the eye. Increasing evidence indicates that microbial agents promote non-infectious uveitis, but the natural history of immune responses to pathogens in patients remains unexplored. We determined intraocular antibodies against pathogens in paediatric uveitis.\n**Methods**\nWe used peptide microarrays containing 3760 linear B-cell epitopes from 196 human pathogens to profile IgG levels in eye fluid biopsies and paired serum samples from 18 Dutch paediatric patients and 6 age-matched controls. We compared intensities of single epitopes and clusters based on overlapping amino acid sequence of peptides. Next-generation sequencing data was obtained to determine the HLA-DRB1∗15:01 genotype.\n**Findings**\nIntraocular antibody profiles largely matched serum profiles and were characterized by high IgG against the conserved PALTAVET-motif of enterovirus family members, as well as broad epitope reactivity against Epstein–Barr virus (EBV). The aqueous humour of patients showed elevated levels of antibodies against peptides containing the RRPFFHPV-motif of Epstein–Barr Virus Nuclear Antigen 1 [EBNA-1]. Antibody levels against the RRPFFHPV-motif of EBNA1 were significantly higher in individuals that carry the HLA-DRB1∗15:01 risk allele of paediatric uveitis.\n**Interpretation**\nIntraocular antibodies against an immunogenic epitope of EBV showed an association with paediatric uveitis, particularly HLA-DRB1∗15:01 positive uveitis, indicating a potential link between EBV-specific immune responses and autoimmune uveitis.\n**Funding**\nFunding for this research was received from Fischer Stichting (UZ2022-3), ODAS (2021-02), LSBS and ANVVB.},\n\tlanguage = {en},\n\turldate = {2025-04-18},\n\tjournal = {eBioMedicine},\n\tauthor = {Hendrikse, Jytte and Bont, Louis J. and Schellekens, Peter A.W.J.F. and De Groot-Mijnes, Jolanda D.F. and De Boer, Joke H. and Kuiper, Jonas J.W.},\n\tmonth = may,\n\tyear = {2025},\n\tkeywords = {Application - Autoimmune Research, PEPperCHIP - Standard, PEPperCHIP Infectious Disease Epitope Micorarray},\n\tpages = {105681},\n}\n\n\n\n","author_short":["Hendrikse, J.","Bont, L. 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