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Sunny Shen, Anita Chan; Toll-like receptors (TLRs) involvement in conjunctival marginal zone lymphomas. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5588. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize the dysregulation of toll-like receptors (TLRs) in extranodal marginal zone lymphoma (EMZL)
A total of 11 extranodal marginal zone lymphoma (EMZL) biopsied from the conjunctiva and orbit, and 5 control reactive lymphoid hyperplasia (RLH) formalin fixed paraffin embedded (FFPE) samples were used. 6 10um thick sections were deparaffinized and RNA extracted using RNeasy FFPE kit (Qiagen) and subjected to the human Toll like receptor (TLR) signalling pathway PCR array (PAHS-018Z, Sabiosciences, Qiagen) which profiles 84 genes central to the TLR mediated signal transduction and innate immunity.
A total of 25/ 84 genes were differentially expressed.TLRs 1,2,4,5,8,and 9 were all significantly down regulated compared to TLR 10 which was more than 4 fold upregulated.7 genes (CD14,IRAK1, LTA, LY96, TLR2, TLR4 and TNFRSF1A) were involved in bacterial specific reponses. In comparison only 2 genes were found to be downregulated in either viral (IFNB1, TLR8) or fungal/parasitic (TLR2, TIRAP) specific responses.9 genes (IRAK1, TIRAP, TLR1,2,4,5,8,9,10) within the TLR MYD88 dependent signalling pathway were significantly dysregulated.7 genes (BTK, FADD, IRAK1, LY96, MAP3k1, NFKBIL1, TNFRSF1A) from the NFkB downstream pathway were significantly dysregulated compared to only 3 genes in the JNK/p38 (ELK1,MAP3ka) and JAK/ STAT (CSF2) pathways.
TLRs are pattern recognition receptor that may interect with specific pathogen associated molecular patterns (PAMPS) to trigger their activation. The finding of significantly down regulated genes involved in bacterial specific responses suggest a bacterial trigger may mediate MZL transformation. Helicobacter pylori is a known pathogenic trigger for EMZL in the stomach. In the eye, chlamydia have been implicated as a trigger for EMZL. TLR 1,6,7,9, and 10 are expressed on B cells in the peripheral blood mononuclear cells (PBMCs) and dysregulation of these TLRs may account for altered proliferation. Our findings of dysregulated MYD88 related genes also supports published data suggesting a role for MYD88 pathway in the pathogenesis of EMZL in the conjunctiva and orbit.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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