Contributions
Abstract: P427
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Immunology
Introduction: The myelin oligodendrocyte glycoprotein (MOG) is an important target of autoantibodies associated with atypical inflammatory demyelinating diseases like acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorders and monophasic or recurrent clinically isolated demyelination. Although experimental studies suggest that antibodies (Ab) against MOG can augment demyelination in rodents and primates, the pathogenic role of human MOG (hMOG) Abs under inflammatory conditions is still unclear. Potential reasons might be that only a subset of hMOG-Abs is also reactive with rodent MOG or a differential binding to MOG epitopes.
Methods: 100 hMOG seropositive samples from 73 patients (27 follow-ups from 25 patients) were screened for their reactivity to rat (rMOG) and mouse MOG (mMOG) with a cell-based assay (CBA). A selection of 40 hMOG positive patients (16 reactive against rMOG and mMOG, 0 against rMOG only, 13 against mMOG only and 11 negative for both) and 18 hMOG seronegative controls were screened for their reactivity on mildly fixed, snap frozen human cerebellum and mouse/rat brain slices via immunohistochemistry (IHC). To test whether this binding was specific we preabsorbed samples with hMOG transfected cells. The effect of purified IgG from three MOG positive patients (one reactive against rMOG) was also investigated in an experimental rat model.
Results: Our present data show that hMOG-Abs are not necessarily reactive to mMOG (72/100, 72%) or rMOG (26/100, 26%) transfected HEK293A cells. Follow-ups did not change their reactivity to rodent MOG. 11/29 mMOG reactive samples and 9/16 rMOG reactive samples showed a positive staining in mouse/rat brain tissue. These samples had significant higher Ab-titre to rMOG/mMOG compared to samples with negative staining. However, we could not detect any association with clinical parameters. Moreover, 25/40 hMOG positive patients had a specific binding in the IHC on human cerebellar slices. Three MOG-IgG preparations were transferred to a rat model of experimental autoimmune encephalitis but none of them induced severe pathological changes.
Conclusion: These data show that not all of the hMOG Ab-positive serum samples are also reactive to rodent MOG. Sera with a higher titre to rodent MOG have a better binding efficiency on rat and mouse brain tissue. With this finding we are now able to further investigate potential pathogenic effects of selected MOG positive serum samples in a suitable animal model.
Disclosure:
Patrick Peschl is enrolled in the graduate program W1206 SPIN funded by the Austrian Science Funds and has no conflict of interest.
Kathrin Schanda: nothing to disclose
Romana Höftberger is funded by Medizinisch-Wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien, Project 15022 and declares no conflicts of interest.
Albert Saiz is funded by Marató de TV3 (20141830) and has received compensation for consulting services and speaker honoraria from Bayer-Schering, Merck-Serono, Biogen-Idec, Sanofi-Aventis, Teva Pharmaceutical Industries Ltd and Novartis.
Monika Bradl is funded by the Austrian Science Funds, project P28476-B30, and has no conflict of interest.
Bleranda Zeka: nothing to disclose.
Kevin Rostasy is funded by project No.14158 from the Jubilaeumsfonds of the Austrian National Bank and has no conflict of interest.
Andreas Lutterotti: nothing to disclose
Thomas Berger: nothing to disclose
Markus Reindl is funded by the graduate program W1206 SPIN funded by the Austrian Science Funds and project BIG WIG MS from the Austrian Federal Ministery of Science, Research and Economy and has no conflict of interest.
Abstract: P427
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Immunology
Introduction: The myelin oligodendrocyte glycoprotein (MOG) is an important target of autoantibodies associated with atypical inflammatory demyelinating diseases like acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorders and monophasic or recurrent clinically isolated demyelination. Although experimental studies suggest that antibodies (Ab) against MOG can augment demyelination in rodents and primates, the pathogenic role of human MOG (hMOG) Abs under inflammatory conditions is still unclear. Potential reasons might be that only a subset of hMOG-Abs is also reactive with rodent MOG or a differential binding to MOG epitopes.
Methods: 100 hMOG seropositive samples from 73 patients (27 follow-ups from 25 patients) were screened for their reactivity to rat (rMOG) and mouse MOG (mMOG) with a cell-based assay (CBA). A selection of 40 hMOG positive patients (16 reactive against rMOG and mMOG, 0 against rMOG only, 13 against mMOG only and 11 negative for both) and 18 hMOG seronegative controls were screened for their reactivity on mildly fixed, snap frozen human cerebellum and mouse/rat brain slices via immunohistochemistry (IHC). To test whether this binding was specific we preabsorbed samples with hMOG transfected cells. The effect of purified IgG from three MOG positive patients (one reactive against rMOG) was also investigated in an experimental rat model.
Results: Our present data show that hMOG-Abs are not necessarily reactive to mMOG (72/100, 72%) or rMOG (26/100, 26%) transfected HEK293A cells. Follow-ups did not change their reactivity to rodent MOG. 11/29 mMOG reactive samples and 9/16 rMOG reactive samples showed a positive staining in mouse/rat brain tissue. These samples had significant higher Ab-titre to rMOG/mMOG compared to samples with negative staining. However, we could not detect any association with clinical parameters. Moreover, 25/40 hMOG positive patients had a specific binding in the IHC on human cerebellar slices. Three MOG-IgG preparations were transferred to a rat model of experimental autoimmune encephalitis but none of them induced severe pathological changes.
Conclusion: These data show that not all of the hMOG Ab-positive serum samples are also reactive to rodent MOG. Sera with a higher titre to rodent MOG have a better binding efficiency on rat and mouse brain tissue. With this finding we are now able to further investigate potential pathogenic effects of selected MOG positive serum samples in a suitable animal model.
Disclosure:
Patrick Peschl is enrolled in the graduate program W1206 SPIN funded by the Austrian Science Funds and has no conflict of interest.
Kathrin Schanda: nothing to disclose
Romana Höftberger is funded by Medizinisch-Wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien, Project 15022 and declares no conflicts of interest.
Albert Saiz is funded by Marató de TV3 (20141830) and has received compensation for consulting services and speaker honoraria from Bayer-Schering, Merck-Serono, Biogen-Idec, Sanofi-Aventis, Teva Pharmaceutical Industries Ltd and Novartis.
Monika Bradl is funded by the Austrian Science Funds, project P28476-B30, and has no conflict of interest.
Bleranda Zeka: nothing to disclose.
Kevin Rostasy is funded by project No.14158 from the Jubilaeumsfonds of the Austrian National Bank and has no conflict of interest.
Andreas Lutterotti: nothing to disclose
Thomas Berger: nothing to disclose
Markus Reindl is funded by the graduate program W1206 SPIN funded by the Austrian Science Funds and project BIG WIG MS from the Austrian Federal Ministery of Science, Research and Economy and has no conflict of interest.