Autoimmune neurologic diseases
Multiple sclerosis (MS) involves immune attacks on the CNS, leading to demyelination, axonal injury and increasing neurological dysfunction. Though both CD4+ and CD8+ T cells are implicated, the particular subsets and their antigenic targets remain largely unknown. In adult-onset MS, distinguishing immune responses that are consequences of, rather than cause of, injury, is difficult. In contrast, pediatric-onset MS offers a unique early window into disease mechanisms given the narrower gap from biological onset. We aim to identify and characterize disease-relevant antigen-specific effector T cell responses to traditional and novel antigenic targets involved early in the MS disease process.
Our group has implicated putative target antigens and T cell subsets in pediatric-onset MS, by following patients from time of an initial presentation with acquired demyelinating syndrome (ADS) and comparing those confirmed to have MS with those who remain monophasic. A CSF proteomic study implicated novel axo-glial apparatus molecules as early injury targets, rather than traditional compact myelin antigens. A series of multiparameter flow-cytometry panels applied to pediatric peripheral blood mononuclear cells (PBMC) revealed that MS children harbor abnormally increased frequencies and pro-inflammatory cytokine responses of particular effector T cell subsets compared to controls.
Our strategy involves developing assays, initially in fresh PBMC samples from adult MS and controls, then miniaturizing the approach and validating it for use in the small numbers of available cryopreserved pediatric PBMC samples to quantify antigen-specific responses including proliferation and cytokine profiles of distinct disease-implicated T cell subsets to both traditionally and newly implicated antigens.
Perelman School of Medicine at the University of Pennsylvania
Post-doctoral research associate
University of Cambridge
Melissa and Paul Anderson President’s Distinguished Professor
University of Pennsylvania and McGill University