Quantitative urinary proteome analysis reveals potential biomarkers for disease activity of Behcet's disease uveitis.

PURPOSE: Behçet's disease-associated uveitis (BDU) is a severe, recurrent inflammatory condition affecting the eye and is part of a systemic vasculitis with unknown etiology, making biomarker discovery essential for disease management. In this study, we intend to investigate potential urinary biomarkers to monitor the disease activity of BDU. METHODS: Firstly, label-free data-dependent acquisition (DDA) and tandem mass tag (TMT)-labeled quantitative proteomics methods were used to profile the proteomes of urine from active and quiescent BDU patients, respectively. For further exploration, the remaining fifty urine samples were analyzed by a data-independent acquisition (DIA) quantitative proteomics method. RESULTS: Twenty-nine and 21 differential proteins were identified in the same urine from BDU patients by label-free DDA and TMT-labeled analyses, respectively. Seventy-nine differentially expressed proteins (DEPs) were significantly changed in other active BDU urine samples compared to those in quiescent BDU urine samples by IDA analysis. Gene Ontology (GO) and protein-protein interaction (PPI) analyses revealed that the DEPs were associated with multiple functions, including the immune and neutrophil activation responses. Finally, seven proteins were identified as candidate biomarkers for BDU monitoring and recurrence prediction, namely, CD38, KCRB, DPP4, FUCA2, MTPN, S100A8 and S100A9. CONCLUSIONS: Our results showed that urine can be a good source of biomarkers for BDU. These dysregulated proteins provide potential urinary biomarkers for BDU activity monitoring and provide valuable clues for the analysis of the pathogenic mechanisms of BDU.

Tubulointerstitial nephritis and uveitis.

PURPOSE OF REVIEW: Tubulointerstitial nephritis and uveitis (TINU) is an important yet underrecognized ocular inflammatory syndrome. This review summarizes key historical publications that identified and defined the syndrome, and more recent literature that reveal the importance of urinary ß2-microglobulin testing and kidney biopsy in the diagnostic evaluation of patients with TINU. Additionally, research studies providing new insights into disease pathogenesis are highlighted. RECENT FINDINGS: In contrast with initial reports of TINU manifesting exclusively as an anterior uveitis in pediatric patients, more recent reports have identified TINU in patients of all ages with a wide range of ocular manifestations. Urinary ß2-microglobulin has emerged as a sensitive and specific laboratory screening test, and the role of kidney biopsy in differentiating TINU from sarcoidosis continues to evolve. Genetic studies have identified HLA-DQA101, HLA-DQB105, and HLA-DRB101 as high-risk alleles and the identification of antimonomeric C-reactive protein antibodies suggests a role for humoral immunity in disease pathogenesis. Management strategies have evolved to include systemic anti-inflammatory treatment as a result of important outcome studies in patients with significant renal and ocular disease. SUMMARY: With greater recognition, understanding, and treatment of this syndrome, both ocular inflammation and renal disease can be better addressed.

Host urinary biomarkers in HIV positive and HIV negative patients with tubercular uveitis and other uveitic diseases.

PURPOSE: To determine if host urinary biomarker profiles could distinguish between tubercular uveitis (TBU) and other uveitic diseases (OUD) in patients with and without HIV infection. METHODS: Concentrations of 29 different host biomarkers were measured in urine samples using the Luminex platform. Data were analyzed to describe differences between patients diagnosed with and without TBU and with and without HIV co-infection. RESULTS: One-hundred-and-eighteen urine samples were collected and 39% participants were diagnosed as TBU+. Mean age TBU+ was 39.3±13.6 years with 45.7% males. Anterior and panuveitis and unilateral involvement were most common. 32.6% were TBU+HIV+ (median CD4+=215) while 40.2% were OUD+HIV+ (median CD4+=234). Only sVEGF3 was decreased in TBU+ versus OUD+ (p=0.03), regardless of HIV status. Some biomarkers were significantly raised in HIV+ TBU+ compared to HIV- TBU+: sIL-6Rα, CD30, sRAGE , sTNFR I&-II, IP-10, MIP-1ß, sEGFR and Ferritin. HIV+ OUD+ had increased sVEGFR3, CD30, sIL-6Rα, IP-10, sTNFR I&-II, Ferritin and Haptoglobin compared to HIV- OUD+. VEGF-A (p = 0.04) was decreased in HIV+ OUD+ versus HIV- OUD+. CONCLUSION: Decreased urinary concentrations of VEGFR3 were observed in TBU+ compared to TBU-. HIV+ individuals demonstrated increased concentrations of multiple urinary analytes when compared to HIV- patients with uveitis.

Tubulointerstitial Nephritis and Uveitis Syndrome: Characterization of Clinical Features.

Purpose: To describe clinical manifestations of patients with tubulointerstitial nephritis and uveitis syndrome (TINU) with a focus on posterior segment findings.Methods: Retrospective chart review.Results: 17 patients were diagnosed with TINU. Ten (59%) were female. Average age at presentation was 19 years (range 7-49). Urine ß2-microglobulin was elevated in all tested patients. Six patients (35%) had isolated anterior uveitis. Eleven (65%) had posterior segment findings. Three (18%) had multifocal choroidal lesions, seven (41%) had disc edema, four (24%) had macular edema, three (18%) had choroidal neovascular membranes, two (12%) had retinal vasculitis, one (6%) had disc neovascularization and vitreous hemorrhage, one (6%) had bilateral posterior scleritis. Eleven (65%) required systemic steroid therapy, seven (41%) required immunomodulatory therapy.Conclusions: TINU occurs in all age groups. Posterior segment manifestations are common. Most patients required systemic steroid therapy, with a significant number requiring long-term systemic immunomodulation. Careful fundus examination is required on all patients with TINU.

Tubulointerstitial nephritis and uveitis syndrome.

PURPOSE OF REVIEW: Tubulointerstitial nephritis and uveitis syndrome (TINU) is a specific form of intraocular inflammation (uveitis) combined with kidney disease that was first described in two patients by Dobrin et al. in 1975. Since then, approximately 200 more cases have been published. The cause of the disease is still unknown. A hypersensitivity reaction is suspected, especially an infection or very rarely a medication reaction is thought to trigger the disease. It is considered to be a rare disease and thus unfortunately is still unfamiliar to most ophthalmologists. Therefore, it is frequently overlooked in the differential diagnosis. In this review we want to show advances in diagnostics and treatment as well as progress in deciphering the pathogenesis. RECENT FINDINGS: Beta-2 microglobulin (Ub2MG) analysis in urine and human leukocyte antigen (HLA) typing is helpful to diagnose TINU cases. A high association of HLA-DRB1*01 has been shown with TINU. A first single case report suggests a common antibody production against ocular and renal proteins. SUMMARY: TINU is a common cause of uveitis among patients who present with bilateral, anterior uveitis of sudden onset. It is more frequent in children and apparently in boys. Although the activity of the eye disease can persist for many months, it is usually controlled with little treatment and the outcome is very good.

Repeat renal biopsy in a girl with tubulointerstitial nephritis and uveitis syndrome.

A Japanese girl aged 8 years who presented with a 2-month history of uveitis subsequently developed tubulointerstitial nephritis. A percutaneous renal biopsy revealed massive interstitial mononuclear cell infiltrates consisting of CD4-positive T cells. Despite administration of topical corticosteroids, the ocular symptoms persisted. Systemic corticosteroid therapy dramatically reduced the ocular symptoms and urinary beta2-microglobulin (beta 2MG) concentration. However, reducing the prednisolone dosage induced recurrence of uveitis associated with increased levels of urinary beta 2MG. The CD4-positive T cell infiltration persisted in the second renal biopsy performed 6 months after the first renal biopsy. These observations suggest that the interstitial cell infiltration persists for a relatively long time in a proportion of patients with tubulointerstitial nephritis and uveitis syndrome (TINU). Although the renal outcome of TINU has been reported to be favorable, prolonged interstitial cell infiltration may affect long-term renal outcome. Selected patients with TINU should be followed with close observation.