Abstract Details

Title Serum Exosomes from Multiple Sclerosis subjects express EBV-derived proteins and activate Monocyte-Derived Macrophages

Topic Multiple Sclerosis

Presentation(s) P2 - Poster Session 2 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-060

Objective We investigated the effect of serum-derived exosomes on primary human blood monocyte-derived macrophages (MDMs) comparing exosomes from healthy donors versus RRMS patients in remission and in relapse (attack), and whether the response was correlated to exosomal EBV protein expression.

Background Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, related to several environmental and genetic risk factors. One of the environmental risk factors is Epstein-Bar virus (EBV) infection. EBV is a gamma-herpes virus that infects around 90% of the population and remains dormant within B lymphocytes throughout life. The vast majority of MS patients are found to be infected with EBV. Exosomes are cell-derived microvesicles that participate in various cellular functions by delivering proteins, mRNA and miRNA to cells. EBV-infected B lymphocytes were found to release exosomes containing the EBV latent membrane protein 1 and 2 (LMP1 and LMP2) and viral miRNA which have the potential to regulate gene expression in receipient cells.

Design/Methods A total of 45 serum-derived exosome preparations were isolated and verified for the expression of exosomal and EBV markers. MDMs were differentiated from monocytes for 7 days then cultured for 24 hours with exosomes, and cell supernatants were collected for cytokine measurement by cytometric bead array (CBA).

Results

After data normalization, we observed a significantly enhanced secretion of the pro-inflammatory cytokine IP-10 induced by RRMS-derived exosomes compared to those of healthy controls (p<0.001, t-test). In addition, there was a positive correlation between IP-10 and TNFα secretion (R²=0.61) by MDMs. Interestingly, exosomes from active patients (in relapse) induced a higher secretion of IL-6 and had a higher expression of LMP1, LMP2A, and EBNA1 with respect to controls.

Conclusions

EBV⁺ exosomes of MS patients induce a more pro-inflammatory cytokine profile by MDMs than those of healthy controls.

Authors/Disclosures
Samia J. Khoury, MD, FAAN (Nehme and Therese Tohme MS Center) PRESENTER	Dr. Khoury has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merk. Dr. Khoury has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Khoury has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for ANA. Dr. Khoury has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Clinical Immunology. The institution of Dr. Khoury has received research support from MENACTRIMS. The institution of Dr. Khoury has received research support from NMSS. The institution of Dr. Khoury has received research support from Office of Naval Research USA. An immediate family member of Dr. Khoury has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file

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