Abstract Details

Title Clinical Correlates of Blood KLRG1+ T cells in Inclusion Body Myositis

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) Neuromuscular and Clinical Neurophysiology (EMG) Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 107

Objective To correlate disease phenotype and severity in inclusion body myositis (IBM) with peripheral blood levels of killer cell lectin-like receptor G1 (KLRG1)+ T cells.

Background Recent advances have further demonstrated autoimmune pathogenic mechanisms in IBM. These include presence of blood anti-NT5c1A autoantibodies, muscle cytotoxic T cell gene expression signatures, and muscle and blood clonal highly differentiated effector cytotoxic KLRG1+ T cells.

Design/Methods We performed a prospective cross-sectional study of 51 IBM patients with ENMC 2011 clinically defined or probable IBM and 20 age-matched healthy comparators. Patient blood was tested for anti-NT5c1A antibodies and immunophenotyped through multiplex flow cytometry for lymphocyte subsets using markers including CD8, CD28, CD57 and KLRG1. Clinical details, demographics, functional data (timed get up, manual muscle testing, hand grip, pinch grip, IBM functional rating scale, modified Rankin score, forced vital capacity, presence of dysphagia, use of assistive devices), and quality of life questionnaires were collected.

Results Blood CD8+ late terminally differentiated effector memory (TEMRA) (CD28-CD57+) T cells constituted a dominant population in IBM, containing very high proportions of KLRG1+ cells. The mean proportion of CD3+ T cells that were CD8+CD28-CD57+KLRG1+ for IBM was 14.4% vs. for age-matched healthy comparators was 6.0% (p<0.001). Preliminary analysis shows that of the functional measures, Timed Get Up (a sensitive measure of proximal weakness) significantly correlated with late TEMRA (p=0.04). (Full results will be presented at the meeting).

Conclusions Our study will further evaluate if increased frequency of blood KLRG1⁺ T cells correlate with markers of disease severity in IBM patients. Identification of these KLRG1+ T cells in IBM and their associated clinical phenotype may give insight into the pathogenesis of IBM and aid in the development of IBM therapeutics.

Authors/Disclosures
Namita Goyal, MD, F�鶹��ýӳ�� (University of California, Irvine) PRESENTER	Dr. Goyal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Goyal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Annexon. Dr. Goyal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abcuro. Dr. Goyal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Goyal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Souffle. Dr. Goyal has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for CSL Behring. Dr. Goyal has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Argenx. Dr. Goyal has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amgen. The institution of Dr. Goyal has received research support from Fulcrum. The institution of Dr. Goyal has received research support from Healey Platform. The institution of Dr. Goyal has received research support from Medicinova. The institution of Dr. Goyal has received research support from Transposon. The institution of Dr. Goyal has received research support from Abcuro. The institution of Dr. Goyal has received research support from Calico. The institution of Dr. Goyal has received research support from Clene. The institution of Dr. Goyal has received research support from Janssen. The institution of Dr. Goyal has received research support from PepGen. The institution of Dr. Goyal has received research support from PTC. The institution of Dr. Goyal has received research support from Roche. The institution of Dr. Goyal has received research support from Sanofi. The institution of Dr. Goyal has received research support from Prilenia. The institution of Dr. Goyal has received research support from RAPA. The institution of Dr. Goyal has received research support from Avidity. Dr. Goyal has received publishing royalties from a publication relating to health care.
Steven A. Greenberg, MD (Brigham and Women's Hospital Neurology)	Dr. Greenberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abcuro, Inc.. Dr. Greenberg has stock in Abcuro. Dr. Greenberg has received intellectual property interests from a discovery or technology relating to health care.
Jonathan Cauchi, MD (University of New Mexico Hospital)	Dr. Cauchi has nothing to disclose.
	No disclosure on file
	No disclosure on file
Marie Wencel, CCRP (University of California, Irvine)	Ms. Wencel has nothing to disclose.
Tyler Irani, MD (Stanford University)	Dr. Irani has nothing to disclose.
Leo H. Wang, MD, PhD, F�鶹��ýӳ�� (University of Washington)	Dr. Wang has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AskBio. Dr. Wang has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Fulcrum Therapeutics. Dr. Wang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Wang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Wang has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Argenx. Dr. Wang has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Avidity. Dr. Wang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Wang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lupin. Dr. Wang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. Dr. Wang has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Scholar Rock. The institution of Dr. Wang has received research support from National Institute of Health. Dr. Wang has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant with US Government.
	No disclosure on file
	No disclosure on file
Tahseen Mozaffar, MD, F�鶹��ýӳ�� (University of California Irvine)	Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Argenx. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amicus. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Grifols. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astellas Gene Therapy. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Applied Therapeutics. The institution of Dr. Mozaffar has received research support from NIH. The institution of Dr. Mozaffar has received research support from Muscular Dystrophy Association. The institution of Dr. Mozaffar has received research support from Sanofi. The institution of Dr. Mozaffar has received research support from Argenx. The institution of Dr. Mozaffar has received research support from Amicus Therapeutics. The institution of Dr. Mozaffar has received research support from Astellas Gene Therpay. The institution of Dr. Mozaffar has received research support from Cartesian. The institution of Dr. Mozaffar has received research support from Cabaletta. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH.

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