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Annemijn Philine Annette Wierenga, Gulcin Gezgin, Els van Beelen, Michael Eikmans, Mieke Versluis, Robert M. Verdijk, Sjoerd van Duinen, Marina Marinkovic, Gregorius P.M. Luyten, Martine J Jager; Soluble HLA in the aqueous humour as risk factor or a marker of inflammation in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):740.
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© ARVO (1962-2015); The Authors (2016-present)
A high HLA expression in uveal melanoma (UM) is part of the prognostically-bad inflammatory phenotype. We wondered whether we could measure soluble HLA (sHLA) in the aqueous humor and whether its presence corresponds to clinical and histopathological characteristics and inflammation, so that it could be used for prognostic purposes.
108 Samples of aqueous humor from UM patients were analysed for detectability and quantity of sHLA using a Luminex assay specific for HLA class I. We performed analyses on eyes positive or negative for sHLA, and correlated concentrations to genetic and clinical parameters. We additionally used tumor-derived mRNA data obtained by Illumina chips.
sHLA was above the detection limit in the aqueous fluid of 19/108 UM-containing eyes. sHLA positive eyes had significantly larger tumors, with a mean tumor prominence of 9.8 mm versus 7.0mm (P<0.0001), and showed more often involvement of the ciliary body (14/19 versus 25/89, P<0.0001). sHLA positive eyes included significantly more tumors with monosomy of chromosome 3 (15/18 versus 48/85, P=0.034), loss of BAP1 staining (16/18 versus 50/79, P=0.036) and gain of chromosome 8q (16/17 versus 43/78, P=0.003). Neither the presence, nor the concentration of sHLA in the aqueous humor was related to a chromosomal 6p duplication (n=82, P=0.811 and n=15, P=0.408 respectively). Survival approached a significant difference between tumors with sHLA and without sHLA in anterior chamber, with sHLA tending to have a worse survival (P = 0.094).When correlating the sHLA findings to mRNA markers representing infiltration (CD3, CD4 and CD8, CD68, n=51), no significant relation was found (P=0.101, P=0.511, P=0.311 and P=0.155). Within the sHLA positive group, CD4 levels were significantly correlated to sHLA levels (n=7, P=0.014). Additionally when comparing the sHLA in the aqueous to HLA-A and HLA-B in mRNA, no significant correlation is found (P=0.155 and 0.228 respectively).
sHLA was present in the aqueous humor of UM-containing eyes, especially in eyes with UM with a high tumor prominence, involvement of the ciliary body, monosomy of chromosome 3, BAP1 loss and a gain of 8q. No relation with the tumor’s lymphocyte infiltrate was observed. Studying factors in aqueous humor may lead to surprising findings and analyses should be expanded to cases undergoing local treatment instead of enucleation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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