Neural autoantibody biomarkers of central nervous system autoimmunity and their clinical and serological accompaniments

Abstract

Several clinical syndromes or phenotypes which arise from central nervous system (CNS) pathology are associated with distinct autoantibodies. The extent to which these phenotypes overlap and the significance of the autoantibodies either as the cause or as biomarkers of disease is important. This thesis aims to evaluate clinical and serological associations of neural autoantibody biomarkers of the CNS with a focus on aquaporin-4 IgG associated neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), myelin oligodendrocyte glycoprotein IgG associated demyelination (MOGAD) and the autoimmune and paraneoplastic encephalitides.

Methods

These studies were conducted at the Mayo Clinic Neuroimmunology laboratory in Minnesota while a doctoral student at the University of Sydney. Clinical and laboratory data were obtained from a clinical laboratory service.

Results

Part A: Demonstrates key serological features of MOGAD and AQP4-IgG NMOSD, highlighting that these are distinct disorders. Chapters 1 and 2 identify distinguishing features including different demographics, lack of antibody co-existence, and a lack of co-existent humoral autoimmunity in MOGAD. Chapter 3 demonstrates the unique neural autoantibody association of N-Methyl-D-aspartate receptor antibody with MOG-IgG in patients with autoimmune encephalitis and MOGAD. Chapter 4 examines factors influencing the change in serostatus of AQP4-IgG.

Part B: Chapters 5 and 6 demonstrates clinical distinctions between MOGAD and AQP4-IgG NMOSD; namely that MOGAD patients do not fulfill the NMOSD seronegative diagnostic criteria and lack the characteristic clinical and radiological features of area postrema syndrome observed in NMOSD.

Part C: Chapter 7 examines the frequency, age and sex associations of autoimmune/paraneoplastic encephalitis autoantibodies.

Conclusions

Together these studies characterize the demographic, clinical and serological associations of neural antibody biomarkers of CNS autoimmunity.