TY - JOUR
T1 - Vitreous proteomics, a gateway to improved understanding and stratification of diverse uveitis aetiologies
AU - Schrijver, Benjamin
AU - Kolijn, P. Martijn
AU - ten Berge, Josianne C. E. M.
AU - Nagtzaam, Nicole M. A.
AU - van Rijswijk, Angelique L. C. T.
AU - Swagemakers, Sigrid M. A.
AU - van der Spek, Peter J.
AU - Missotten, Tom O. A. R.
AU - van Velthoven, Mirjam E. J.
AU - de Hoog, Joeri
AU - van Hagen, P. Martin
AU - Langerak, Anton W.
AU - Dik, Willem A.
N1 - Publisher Copyright: © 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.
PY - 2021
Y1 - 2021
N2 - Purpose: The vitreous proteome might provide an attractive gateway to discriminate between various uveitis aetiologies and gain novel insights into the underlying pathophysiological processes. Here, we investigated 180 vitreous proteins to discover novel biomarkers and broaden disease insights by comparing (1). primary vitreoretinal lymphoma ((P)VRL) versus other aetiologies, (2). sarcoid uveitis versus tuberculosis (TB)-associated uveitis and (3). granulomatous (sarcoid and TB) uveitis versus other aetiologies. Methods: Vitreous protein levels were determined by proximity extension assay in 47 patients with intraocular inflammation and a prestudy diagnosis (cohort 1; training) and 22 patients with a blinded diagnosis (cohort 2; validation). Differentially expressed proteins identified by t-tests on cohort 1 were used to calculate Youden’s indices. Pathway and network analysis was performed by ingenuity pathway analysis. A random forest classifier was trained to predict the diagnosis of blinded patients. Results: For (P)VRL stratification, the previously reported combined diagnostic value of IL-10 and IL-6 was confirmed. Additionally, CD70 was identified as potential novel marker for (P)VRL. However, the classifier trained on the entire cohort (cohort 1 and 2) relied primarily on the interleukin score for intraocular lymphoma diagnosis (ISOLD) or IL-10/IL-6 ratio and only showed a supportive role for CD70. Furthermore, sarcoid uveitis displayed increased levels of vitreous CCL17 as compared to TB-associated uveitis. Conclusion: We underline the previously reported value of the ISOLD and the IL-10/IL-6 ratio for (P)VRL identification and present CD70 as a potentially valuable target for (P)VRL stratification. Finally, we also show that increased CCL17 levels might help to distinguish sarcoid uveitis from TB-associated uveitis.
AB - Purpose: The vitreous proteome might provide an attractive gateway to discriminate between various uveitis aetiologies and gain novel insights into the underlying pathophysiological processes. Here, we investigated 180 vitreous proteins to discover novel biomarkers and broaden disease insights by comparing (1). primary vitreoretinal lymphoma ((P)VRL) versus other aetiologies, (2). sarcoid uveitis versus tuberculosis (TB)-associated uveitis and (3). granulomatous (sarcoid and TB) uveitis versus other aetiologies. Methods: Vitreous protein levels were determined by proximity extension assay in 47 patients with intraocular inflammation and a prestudy diagnosis (cohort 1; training) and 22 patients with a blinded diagnosis (cohort 2; validation). Differentially expressed proteins identified by t-tests on cohort 1 were used to calculate Youden’s indices. Pathway and network analysis was performed by ingenuity pathway analysis. A random forest classifier was trained to predict the diagnosis of blinded patients. Results: For (P)VRL stratification, the previously reported combined diagnostic value of IL-10 and IL-6 was confirmed. Additionally, CD70 was identified as potential novel marker for (P)VRL. However, the classifier trained on the entire cohort (cohort 1 and 2) relied primarily on the interleukin score for intraocular lymphoma diagnosis (ISOLD) or IL-10/IL-6 ratio and only showed a supportive role for CD70. Furthermore, sarcoid uveitis displayed increased levels of vitreous CCL17 as compared to TB-associated uveitis. Conclusion: We underline the previously reported value of the ISOLD and the IL-10/IL-6 ratio for (P)VRL identification and present CD70 as a potentially valuable target for (P)VRL stratification. Finally, we also show that increased CCL17 levels might help to distinguish sarcoid uveitis from TB-associated uveitis.
KW - (P)VRL
KW - intraocular
KW - proteomics
KW - proximity extension assay
KW - sarcoidosis
KW - tuberculosis
KW - uveitis
KW - vitreous
UR - http://www.scopus.com/inward/record.url?scp=85111381307&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/aos.14993
DO - https://doi.org/10.1111/aos.14993
M3 - Article
C2 - 34318583
SN - 1755-375X
JO - Acta ophthalmologica
JF - Acta ophthalmologica
ER -