Research Projects

NMOSD is an inflammatory CNS disorder associated with aquaporin-4 antibodies (AQP4-Ab) against principal water channel on astrocyte foot processes. The prevalence among Asian population is 15-49 per million. The AQP4-Ab has been detected in 70-90% of NMOSD patient depending on ethnicity. The 4-11% (20-40% of AQP4-Ab negative) patients have been positive for myelin oligodendrocyte glycoprotein (MOG) antibody and 15-20% of NMOSD patients do not show any antibody suggesting a different pathophysiology. The pathology of MOG-Ab disease is primarily through demyelination without involvement of astrocytes. The age at onset, disease presentation, severity, response to treatment, relapse and prognosis differs among AQP4-Ab+, MOG-Ab+ and seronegative patients. There are very few studies exploring possible role of T cells subsets in pathobiology of NMOSD which also mainly focused on AQP4-Ab+ group and rest two groups MOG-Ab+ and seronegative NMOSD were not well characterized. The multiple sclerosis and NMO clinic of NIMHANS receives large number of demyelination patients and institute is providing clinical, diagnostic, and therapeutic management including therapeutic plasma exchange (TPE). The T follicular helper (Tfh) cells are involved in activation of antibody producing B cells. Tfh cells express cell surface phenotype including CXC chemokine receptor 5 (CXCR5), programmed death 1 (PD-1), inducible co-stimulator (ICOS), and CD40. T regulatory cells (Tregs) maintain immune regulation and homeostasis mainly via secretion of immunosuppressive cytokines. The dysregulation of generation and function of Tfh cell is associated with autoimmunity. The Tfh and Tregs cells levels have been shown to be altered in peripheral blood of various autoimmune diseases like SLE, rheumatoid arthritis, primary Sjogren syndrome, ankylosing spondylitis, and myasthenia gravis. Tfh have been reported higher and Tregs reported lower levels in NMOSD patients than healthy controls. A clear and better understanding of role of Tfh and Treg subsets is crucial to explore numerous facets of pathobiology of NMOSD for developing approaches to modulate these cells for clinical benefit. Acute attacks of NMOSD are managed by steroids with or without TPE or TPE alone. The TPE is now well accepted therapeutic option by removing pathological substance and by inducing immunomodulation. The NMOSD with production of antibodies and complement mediated astrocyte and neuronal damage is considered Th2 and Th17 mediated disease and TPE helps to restore Th2 pathway. The effect of TPE on Th1/Th2/Th17 pathway can provide better insight for therapeutic effect of TPE This study will assess pathobiology of NMOSD by analyzing Tfh and Tregs cells and Th1/Th2/Th17 cytokines on clinical presentation, response to immunomodulation, relapse and prognosis among AQP4-Ab+, AQP4-Ab negative and MOG-Ab+ and seronegative NMOSD. Age and gender matched healthy blood donors will serve as baseline controls for study markers