Combined cellular and soluble mediator analysis for improved diagnosis of vitreoretinal lymphoma
2019
Purpose: Primary vitreoretinal lymphoma [(P)VRL]) is a rare malignancy of the
eye localized in the retina, vitreous or choroid. Here, we aim to determine the
value of the combination of innovative diagnostic methods for accurate
differentiation between (P)VRL and non-(P)VRL in patients with suspect uveitis
or vitritis.
Methods: Multicolour flow cytometric immunophenotyping of cells in the
vitreous samples was performed using the EuroFlow small sample tube.
Additionally, cytokines/chemokines and growth factors were measured in the
vitreous specimens using a multiplex immunoassay. Data were evaluated in
predefined clinical subgroups using OMNIVIZ unsupervised Pearson’s correlation
visualization and unsupervised heatmap analysis.
Results: A total of 53 patients were prospectively included in the period 2012–
2015. In the (P)VRL subgroup (n = 10), nine cases showed aberrant surface
membrane immunoglobulin (SmIg) light chain expression. In the non-(P)VRL
group (n = 43) clearly skewed SmIg light chain expression was observed in two
multiple sclerosis-related uveitis cases, but not in other uveitis types. Soluble
mediator measurement revealed high interleukin (IL)-10/IL-6 ratios, and high
IL-1RA levels in 9/10 (P)VRL cases, but not in any non-(P)VRL case. Further
correlation and heatmap analysis revealed a minimal signature of cellular
parameters (CD19+ B cells, aberrant SmIg light chain expression) and cytokine
parameters (IL-10/IL-6 ratio >1, high IL-10, high IL-1 RA, high monocyte
chemotactic protein-1, high macrophage inflammatory protein-1b) to reliably
distinguish (P)VRL from non-(P)VRL.
Conclusion: Here, we show the power of a combined cellular and proteomics
strategy for detecting (P)VRL in vitreous specimens, especially in cases with
minor cellular (P)VRL infiltrates.
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