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Issue: Issue 3 (2016) – Supplement 1


Debate

Anti B cell or non specific anti B+T therapy

Author(s):
Hans-Peter Hartung
Abstract:
Point of view: Pro Anti B
More than a decade ago the dominant theories on the etiology and pathogenesis of MS revolved around a prime role of T cells that would recognize target autoantigens in the brain and orchestrate inflammatory insults on CNS parenchyma. Subsequently, numerous lines of research advanced robust evidence for a role of humoral autoimmunity and B lymphocytes in driving or contributing to the disease process. These included histopathological analyses of MS brains detecting immunoglobulin and complement deposits as well as B cells in lesions, and the retrieval of myelin-reactive antibodies and B cells in blood and CSF. The most convincing evidence came from therapeutic studies with the B cell depleting monoclonal anti-CD20 antibody rituximab in RRMS. This highly effective monoclonal induced early suppression of inflammatory disease activity. This temporal profile suggested an action on B cell function as antigen presenters and instructors of T cells rather than a modifying effect on autoantibody production. The clinical development of the humanized anti-CD 20 antibody ocrelizumab culminating in the two OPERA studies in RRMS completed last year replicated the marked therapeutic effects achieved with rituximab in the earlier phase 2 trial. Very interestingly, ocrelizumab also appeared effective in a recently completed phase 3 trial in PPMS. These results raise a number of questions as to the role of B cells in the pathogenesis of this disease type.

Special Issue on Controversies in Neurology. From the 10th World Congress on Controversies in Neurology (CONy), Lisbon, Portugal. 17–20 March 2016.

International Journal of Clinical Neurosciences and Mental Health 2016; 3(Suppl. 1):D11
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