8299
Targeted CSF Proteomics As a Tool for Analyzing Immunophenotype Heterogeneity in Multiple Sclerosis

Friday, June 3, 2022: 3:50 PM
Potomac A (Gaylord National Resort & Convention Center)
Saurabh Kumar, BS , Department of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, Department of Neurology, University of Massachusetts Memorial Medical Center, Worcester, MA
Khashayar Afshari, MD, MPH , Department of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA
Alexandra Rabin, BA , Department of Neurology, University of Massachusetts Memorial Medical Center, Worcester, MA
Farnaz Khalighinejad, MD , Department of Neurology, University of Massachusetts Memorial Medical Center, Worcester, MA
Nimmy Francis, PhD, MBBS , Department of Neurology, University of Massachusetts Memorial Medical Center, Worcester, MA
Fatima Qutab, N/A , Department of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA
Danny Kwong, N/A , Department of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA
Irina Radu, MD , Division of Cardiovascular Medicine, University of Massachusetts Chan Medical School, Worcester, MA
Idanis Berrios-Morales, MD , Department of Neurology, University of Massachusetts Memorial Medical Center, Worcester, MA
Christopher Hemond, MD , Department of Neurology, University of Massachusetts Memorial Medical Center, Worcester, MA
Dalia Abou Zeki, MD , Atrium Health Neurosciences Institute Neurology Kenilworth, Charlotte, NC
Jillian M Richmond, PhD , Department of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA
Carolina Ionete, MD, PhD , Department of Neurology, University of Massachusetts Memorial Medical Center, Worcester, MA



Background: Multiple Sclerosis (MS) is an autoimmune disorder characterized by central nervous system demyelination. Given the heterogeneity of MS clinical presentation, patients often try multiple treatment regimens before achieving satisfactory disease control. Common therapeutics used today include alemtuzumab (anti-CD52) and ocrelizumab (anti-CD20).

Objectives: We aspire to better characterize how immunological phenotypes correlate with MS presentation. We hypothesize that predominance of specific immune cell subsets and their associated cytokines and receptors can serve as biomarkers for autoimmune disease activity and responsiveness to therapeutics.

Methods: We have developed a high-parameter cellular immunophenotyping pipeline utilizing 1) spectral flow cytometry with 19 immunophenotyping markers and 2) oligonucleotide-linked-antibody proteomics (Olink Proteomics) for soluble cytokine analysis. Olink allows high-fidelity, simultaneous analysis of 90+ inflammation-associated proteins within circulation. Using this pipeline, we analyzed n=15 patient immune cells by flow cytometry including 9 relapsing remitting MS (RRMS) patients. n=64 cerebrospinal fluid (CSF) samples of patients with neuroinflammatory conditions, of which 40 were diagnosed with MS, were analyzed via Olink.

Results: We observed that RRMS patients exhibited decreased levels of monocyte stimulating markers (CCL2, CCL13) relative to non-MS patients. Additionally, we observed sex-based differences among RRMS patients where males expressed significantly higher IL-8 and females expressed higher Artemin (glial cell-derived neurotrophic factor in the TGF-β superfamily). Furthermore, significantly differential markers in SPMS and PPMS were observed relative to other patients. Likewise, preliminary multivariate analysis demonstrated clustering between RRMS patients treated with alemtuzumab versus ocrelizumab. Finally, CXCL10 and CXCL11 were elevated in RRMS patient CSF in addition to their cognate receptor, CXCR3, on T cells.

Conclusions: Using our pipeline, we were able to analyze the heterogeneity between MS cases. Our data suggest that decreased monocyte activity may characterize RRMS relative to other neuroinflammatory conditions. Furthermore, given that male sex is a poor prognostic factor for MS, IL-8 along with the TGF-β family and associated pathways may mediate this difference. Similarly, increased binding between CXCL10/11 to CXCR3 on T cells may contribute to inflammatory infiltrates in RRMS patients. Given more patient data, this pipeline has the potential to elucidate mechanisms of MS neuroinflammation and better inform clinical decisions.

See more of: Whitaker Research Track
See more of: Whitaker Research Track
<< Previous Abstract | Next Abstract