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Simon Epps, Natalie Coplin, Philip J Luthert, Andrew D Dick, Sarah E. Coupland, Lindsay B Nicholson; Immunohistochemical examination of the B lymphocyte infiltrate in human uveitis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):553.
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© ARVO (1962-2015); The Authors (2016-present)
Ectopic lymphoid-like structures (ELS) are focal aggregations of B lymphocytes with features of secondary lymphoid follicles that develop in non-lymphoid tissue. ELS are found in chronic inflammatory disorders, and with respect to uveitis, have been demonstrated in murine experimental autoimmune uveoretinitis and equine recurrent uveitis but have yet to be shown in man. This histopathological observational study examined a series of 14 human uveitic eyes by immunohistochemistry (IHC) to assess the nature of B cell infiltration and determine whether features of ELS were present.
14 formalin-fixed paraffin-embedded enucleated human eyes from 14 patients with uveitis were obtained from the Liverpool Ocular Oncology Biobank (Liverpool, UK) and Moorfields Biobank (London, UK) with ethical approval. Samples were identified by reviewing histopathology reports from each institution and selected if reported to contain visible lymphocytes within the uveoretina on haematoxylin- and eosin-stained sections. Further sections were examined by IHC for CD3+ T cells and CD20+ B cells. If CD20+ cells were present additional IHC was performed for lymphoid follicle markers CD21, CD23, BCL6 and AID. ELS were defined as focal B and T cell aggregates with T/B cell segregation and a CD21+ network.
B cells were present in the majority of cases (10 out of 14, 71%). The B cell infiltrate was either diffuse (3 out of 14 cases, 21%), focal (5 out of 14 cases, 36%), or focal with features of ELS (2 out of 14 cases, 14%). B cells were most frequently seen within the uvea and not the retina (uvea only: 9 out of the 10 cases where B cells were evident, 90%; uvea and retina 1 out of 10 cases, 10%).
Within the uvea of patients with uveitis a B cell infiltrate is often present as either diffuse, focal or organised aggregations with T cells and lymphoid follicle markers consistent with ELS. These ELS-like structures within the uvea may represent sites of antigen-specific B cell proliferation, mutation and maturation, and could be of clinical relevance with respect to B-cell immunomodulatory therapies in uveitis.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
Figure: IHC image of choroid of patient 2 showing focal CD20+ B and CD3+ T cell infiltrate with CD21+ follicular dendritic cell network, CD23+ follicular B cells and BCL6 expression consistent with an ELS (x400 magnification)
Table summarising IHC data; + indicates present, - indicates absent
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