Abstract Details

Title Limited Effects of Interferon ß-1a in an IgG-driven Model of Multiple Sclerosis Pathology

Topic Multiple Sclerosis

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-037

Objective To examine whether interferon β-1a (IFNβ-1a), an approved MS medication, can limit lesion formation following intracerebral injection (ICI) of MS recombinant antibody and human complement (HC).

Background Persistent oligoclonal IgG is a signature of MS disease pathology. We produced a panel of monoclonal recombinant antibodies (rAbs) from MS CSF plasmablast clones recovered from MS patients. A subset of these rAbs bind to myelin and initiate complement-dependent demyelination in ex vivo slice cultures and in vivo mouse brain.

Design/Methods C57BL/6 mice were treated with IFNβ-1a or PBS by subcutaneous injection (every third day) beginning 8 days prior to ICI and continuing for an additional 28 days. Demyelinating lesions were induced by ICI of myelin-specific MS rAb (MS#30) or isotype control rAb 2B4 (IC) and 20% HC. T1-gadolinium (T1-gad) and T2 MRI imaging was performed prior to ICI (day 0) and on days 1, 7 and 28 post-injection. Animals were sacrificed post MRI, fixed and sectioned and stained for myelin damage (anti-MBPQD9) and immune cell infiltration.

Results The injection of MS#30+HC into mouse brain produced T2-weighted and T1-gad lesions that were significantly greater than that observed with IC+HC. MS#30 lesions demonstrated large areas of diffuse anti-MBPQD9 staining and large CD68+ immune cell infiltrates. Treatment with IFNβ-1a had no discernable effect on T2 and T1-gadolinum lesion volumes, myelin loss, or levels of CD68 infiltration. Treatment also did not affect the timing of lesion resolution.

Conclusions IFNβ-1a treatment did not lessen lesion size, blood-brain barrier (BBB) permeability, or immune cell infiltration in an intrathecal model of Ab-driven MS demyelination. The lack of effect of IFNβ-1a is likely due to the peripheral rather than central action of the cytokine on immune cell activation and BBB breakdown. Intrathecal antibody-mediated MS pathology may direct lesion formation that is recalcitrant to some MS therapeutics.

Authors/Disclosures
Jeffrey L. Bennett, MD, PhD, FAAN (University of Colorado School of Medicine) PRESENTER	Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immpact Bio. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Chugai. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Beigene. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Imcyse. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MIAC. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CorEvitas. Dr. Bennett has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Alexion. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Vindico. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Touch IME. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Efficient LLC. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Pavich. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Marie Bush. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Marks Gray. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Knight, Nicastro, MacKay. The institution of Dr. Bennett has received research support from Alexion. The institution of Dr. Bennett has received research support from Genentech. Dr. Bennett has received intellectual property interests from a discovery or technology relating to health care. Dr. Bennett has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Gregory Owens, PhD	Dr. Owens has received intellectual property interests from a discovery or technology relating to health care.

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