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UBC Theses and Dissertations

The role of antibody testing for anti-natalizumab and anti-aquaporin-4 antibodies in demyelinating disorders Fronda, Anna Grace


Antibody testing in medicine is utilized for diverse purposes that are highly dependent on the type of antibody and the disease to which it is related. This thesis examines testing for antibodies in relation to two demyelinating diseases of the central nervous system. Anti-natalizumab antibodies in multiple sclerosis (MS) patients treated with natalizumab, a therapeutic humanized monoclonal antibody against a cell adhesion protein, are associated with increased infusion-related reactions and reduced treatment efficacy. While initial testing for this anti-biological antibody is recommended before 24 weeks of treatment, a seropositive result warrants multiple testing throughout the treatment duration to distinguish transient from persistent antibody responses. This is significant because patients with a transient antibody response may still benefit from natalizumab treatment in the long term whereas patients with persistent antibodies will not and, therefore, should discontinue treatment. A Biacore assay for anti-natalizumab antibodies that uses surface plasmon technology is suitable for a large amount of samples and to study antibody affinity. As such, this assay was used to demonstrate that in a single patient with a transient antibody response, seroconversion to antibody negative is indicative of immune tolerance to natalizumab. The second antibody under investigation is the pathological autoantibody, anti-aquaporin-4 antibody. It is the most specific and sensitive serum biomarker for neuromyelitis optica (NMO) and NMO spectrum disorders. However, there is, at present, a lack of standardization with the currently available methods to measure this antibody. This is seen in the varying assay senstitivity and specificities between labs even with commercial assays, as well as the differing results with repeat testing of samples. Along with the formulation of diagnostic criteria that better distinguishes NMO from MS, an effort should be made to improve current immunoassays and to development more sensitive techniques to measure anti-aquaporin-4 antibodies in patient serum.

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