Anatomy and Neuroscience - Research Publications

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End date: 2022 × Author: Monif, Mastura × Author: Butzkueven, Helmut × Author: Kalincik, Tomas ×

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    Fast and safe: Optimising multiple sclerosis infusions during COVID-19 pandemic
    Rath, L ; Bui, MV ; Ellis, J ; Carey, J ; Baker, J ; Taylor, L ; Fernando, H ; Taylor, N ; Savage, P ; Richards, J ; Zhong, M ; Kalincik, T ; Skibina, O ; Wesselingh, R ; Nguyen, A-L ; Monif, M ; Butzkueven, H ; van der Walt, A (ELSEVIER SCI LTD, 2021-01)
    BACKGROUND: The COVID-19 pandemic challenges multiple sclerosis services to be innovative in delivering infusible therapies. To reduce time in clinical settings, and potential staff or space losses, we implemented rapid infusion protocols for selected patients. OBJECTIVE: To analyse the rate of infusion related reactions and patient experience of rapid infusions of natalizumab and ocrelizumab. To document time reduction patients spent in clinical settings during the COVID-19 pandemic. METHODS: Patients with prior exposure to at least three natalizumab or two 300mg ocrelizumab infusions were approved for rapid protocols. A retrospective audit and survey were completed. RESULTS: We analysed 269 rapid natalizumab infusions and 100 rapid ocrelizumab infusions. Infusion related reactions during the natalizumab or ocrelizumab infusions occurred in two patients (1.52%) and eight patients (8%), respectively. All infusion related reactions were mild to moderate and did not require infusion discontinuation. No infusion reactions occurred during the post-infusion observation. Patient experience was positive. CONCLUSION: Frequency or severity of infusion related reactions in rapid infusions were no different compared to published data. In the setting of COVID-19, pandemic rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis.
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    Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination
    Tea, F ; Lopez, JA ; Ramanathan, S ; Merheb, V ; Lee, FXZ ; Zou, A ; Pilli, D ; Patrick, E ; van der Walt, A ; Monif, M ; Tantsis, EM ; Yiu, EM ; Vucic, S ; Henderson, APD ; Fok, A ; Fraser, CL ; Lechner-Scott, J ; Reddel, SW ; Broadley, S ; Barnett, MH ; Brown, DA ; Lunemann, JD ; Dale, RC ; Brilot, F ; Sinclair, A ; Kermode, AG ; Kornberg, A ; Bye, A ; McGettigan, B ; Trewin, B ; Brew, B ; Taylor, B ; Bundell, C ; Miteff, C ; Troedson, C ; Pridmore, C ; Spooner, C ; Yiannikas, C ; O'Gorman, C ; Clark, D ; Suan, D ; Jones, D ; Kilfoyle, D ; Gill, D ; Wakefield, D ; Hofmann, D ; Mathey, E ; O'Grady, G ; Jones, HF ; Beadnall, H ; Butzkueven, H ; Joshi, H ; Andrews, I ; Sutton, I ; MacIntyre, J ; Sandbach, JM ; Freeman, J ; King, J ; O'Neill, JH ; Parratt, J ; Barton, J ; Garber, J ; Ahmad, K ; Riney, K ; Buzzard, K ; Kothur, K ; Cantrill, LC ; Menezes, MP ; Paine, MA ; Marriot, M ; Ghadiri, M ; Boggild, M ; Lawlor, M ; Badve, M ; Ryan, M ; Aaqib, M ; Shuey, N ; Jordan, N ; Urriola, N ; Lawn, N ; White, O ; McCombe, P ; Patel, R ; Leventer, R ; Webster, R ; Smith, R ; Gupta, S ; Mohammad, SS ; Pillai, S ; Hawke, S ; Simon, S ; Calvert, S ; Blum, S ; Malone, S ; Hodgkinson, S ; Nguyen, TK ; Hardy, TA ; Kalincik, T ; Ware, T ; Fung, VSC ; Huynh, W (BMC, 2019-09-03)
    Over recent years, human autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG Ab) have been associated with monophasic and relapsing central nervous system demyelination involving the optic nerves, spinal cord, and brain. While the clinical relevance of MOG Ab detection is becoming increasingly clear as therapeutic and prognostic differences from multiple sclerosis are acknowledged, an in-depth characterization of human MOG Ab is required to answer key challenges in patient diagnosis, treatment, and prognosis. Herein, we investigated the epitope, binding sensitivity, and affinity of MOG Ab in a cohort of 139 and 148 MOG antibody-seropositive children and adults (n = 287 patients at baseline, 130 longitudinal samples, and 22 cerebrospinal fluid samples). MOG extracellular domain was also immobilized to determine the affinity of MOG Ab. MOG Ab response was of immunoglobulin G1 isotype, and was of peripheral rather than intrathecal origin. High affinity MOG Ab were detected in 15% paediatric and 18% adult sera. More than 75% of paediatric and adult MOG Ab targeted a dominant extracellular antigenic region around Proline42. MOG Ab titers fluctuated over the progression of disease, but affinity and reactivity to Proline42 remained stable. Adults with a relapsing course intrinsically presented with a reduced immunoreactivity to Proline42 and had a more diverse MOG Ab response, a feature that may be harnessed for predicting relapse. Higher titers of MOG Ab were observed in more severe phenotypes and during active disease, supporting the pathogenic role of MOG Ab. Loss of MOG Ab seropositivity was observed upon conformational changes to MOG, and this greatly impacted the sensitivity of the detection of relapsing disorders, largely considered as more severe. Careful consideration of the binding characteristics of autoantigens should be taken into account when detecting disease-relevant autoantibodies.