Transcriptomic and proteomic analysis of iris tissue and aqueous humor in juvenile idiopathic arthritis-associated uveitis. (June 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Journal of autoimmunity. Volume 100(2019)
• Page Start: 75
• Page End: 83
• Publication Date: 2019-06
• Subjects: Juvenile idiopathic arthritis -- Uveitis -- B cells -- Cytokines -- Plasma cell niche -- HLA-B27; ANA anti nuclear antibodies -- APRIL a proliferation-inducing ligand -- AU anterior uveitis -- AAU acute anterior uveitis -- AqH aqueous humor -- BAFF B cell-activating factor -- BCMA B cell maturation antigen -- BSA bovine serum albumin -- CD cluster of differentiation -- cDNA complementary desoxyribonucleic acid -- CHAPS 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate -- DE differentially expressed -- DMARD disease-modifying anti-rheumatic drug -- DTT Dithiothreitol -- f female -- EBF1 early B cell factor 1 -- FDR false discovery rate -- fw forward -- GAPDH Glyceraldehyde 3-phosphate dehydrogenase -- Gpr83 G Protein-Coupled Receptor 83 -- HLA human leukocyte antigen -- HKG housekeeping gene -- ID inhibitor of DNA binding -- Ig immunoglobulin -- IL interleukin -- ILAR International League of Associations for Rheumatology -- IOP intraocular pressure -- JIA juvenile idiopathic arthritis -- JIAU juvenile idiopathic arthritis-associated uveitis -- LC-IMS liquid chromatography coupled ion mobility mass spectrometry -- LLPC long-lived plasma cell -- m male -- mRNA messenger RNA -- Mmrn2 Multimerin 2 -- MTX methotrexate -- MZB1 marginal zone and B1 cell-specific protein -- Nedd9 Neural Precursor Cell Expressed -- PC plasma cell -- PCA principle component analysis -- POAG primary open-angle glaucoma -- qRT-PCR quantitative real-time polymerase chain reaction -- RA rheumatoid arthritis -- RF rheumatoid factor -- RIN RNA integrity number -- rlog regularized logarithm -- RNA ribonucleic acid -- RNA-Seq RNA Sequencing -- rv reverse -- SD standard deviation -- SE standard error -- SDC-1 Syndecan-1 -- SDS-PAGE Sodium dodecyl sulfate polyacrylamide gel electrophoresis -- SLE systemic lupus erythematosus -- SS Sjögren syndrome -- SUN standardization of uveitis nomenclature -- TBS-T Tris-buffered saline with Tween 20 -- TCEP tris(2-carboxyethyl)phosphine) -- Th T-helper -- UPLC Ultra Performance Liquid Chromatography; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2019.03.004
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: 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. Highlights: Iris of juvenile idiopathic arthritis-associated uveitis (JIAU) is characterized by distinct gene and protein expression. Gene and proteome expression point to presence and longevity of B cells and plasma cells in the iris of JIAU patients. Elevated BAFF and APRIL concentrations in aqueous humor of JIA-uveitis may contribute to longevity of B and plasma cells.