Transcriptomic and proteomic analysis of iris tissue and aqueous humor in juvenile idiopathic arthritis-associated uveitis.

Wildschütz, Lena; Ackermann, Doreen; Witten, Anika; Kasper, Maren; Busch, Martin; Glander, Shirin; Melkonyan, Harutyun; Walscheid, Karoline; Tappeiner, Christoph; Thanos, Solon; Barysenka, Andrei; Koch, Jörg; Heinz, Carsten; Laffer, Björn; Bauer, Dirk; Stoll, Monika; König, Simone; Heiligenhaus, Arnd (2019). Transcriptomic and proteomic analysis of iris tissue and aqueous humor in juvenile idiopathic arthritis-associated uveitis. Journal of autoimmunity, 100, pp. 75-83. Elsevier 10.1016/j.jaut.2019.03.004

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Gene and protein expression profiles of iris biopsies, aqueous humor (AqH), and sera in patients with juvenile idiopathic arthritis-associated uveitis (JIAU) in comparison to control patients with primary open-angle glaucoma (POAG) and HLA-B27-positive acute anterior uveitis (AAU) were investigated. Via RNA Sequencing (RNA-Seq) and mass spectrometry-based protein expression analyses 136 genes and 56 proteins could be identified as being significantly differentially expressed (DE) between the JIAU and POAG group. Gene expression of different immunoglobulin (Ig) components as well as of the B cell-associated factors ID3, ID1, and EBF1 was significantly upregulated in the JIAU group as compared to POAG patients. qRT-PCR analysis showed a significantly higher gene expression of the B cell-related genes CD19, CD20, CD27, CD138, and MZB1 in the JIAU group. At the protein level, a significantly higher expression of Ig components in JIAU than in POAG was confirmed. The B cell-associated protein MZB1 showed a higher expression in JIAU patients than in POAG which was confirmed by western blot analysis. Using bead-based immunoassay analysis we were able to detect a significantly higher concentration of the B cell-activating and survival factors BAFF, APRIL, and IL-6 in the AqH of JIAU and AAU patients than in POAG patients. The intraocularly upregulated B cell-specific genes and proteins in iris tissue suggest that B cells participate in the immunopathology of JIAU. The intracameral environment in JIAU may facilitate local effector and survival functions of B cells, leading to disease course typical for anterior uveitis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology

UniBE Contributor:

Tappeiner, Christoph

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0896-8411

Publisher:

Elsevier

Language:

English

Submitter:

Christoph Tappeiner

Date Deposited:

04 Dec 2019 10:34

Last Modified:

04 Dec 2019 10:43

Publisher DOI:

10.1016/j.jaut.2019.03.004

PubMed ID:

30885419

Uncontrolled Keywords:

B cells Cytokines HLA-B27 Juvenile idiopathic arthritis Plasma cell niche Uveitis

BORIS DOI:

10.7892/boris.135566

URI:

https://boris.unibe.ch/id/eprint/135566

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