CD19 as a molecular target in CNS autoimmunity

Abstract

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are the most prevalent neuroinflammatory diseases of the central nervous system (CNS). The immunological cascade of these disorders is complex, and the exact spatial and temporal role of different immune cells is not fully understood. Although MS has been considered for many years to be primarily T cell driven, it is well established that B cells and the humoral immune response play an important role in its pathogenesis. This has long been evident from laboratory findings that include the presence of oligoclonal bands in the CSF. In NMO the importance of the humoral immune system appears even more obvious as evidenced by pathogenic antibodies against aquaporin 4 (AQP4). Besides their capacity to mature into antibody-producing plasma cells, B cells are potent antigen presenting cells to T lymphocytes and they can provide soluble factors for cell activation and differentiation to other immune-competent cells. In MS and NMO, there are substantial data from clinical trials that B cell depletion with CD20-directed agents is effective and relatively safe. Plasma cells, which produce antibodies against molecular targets expressed by the host, but which also provide humeral immune responses against pathogens, are not targeted by anti-CD20 therapies. Therefore the depletion of CD19-expressing cells would offer potential advantages with regard to efficacy, but potentially higher risks with regard to infectious complications. This review will outline the rationale for CD19 as a molecular target in CNS autoimmunity. The current stage of drug development is illustrated. Potential safety concerns will be discussed.

Differences in Intercellular Communication During Clinical Relapse and Gadolinium-Enhanced MRI in Patients With Relapsing Remitting Multiple Sclerosis: A Study of the Composition of Extracellular Vesicles in Cerebrospinal Fluid

“…Two other markers examined were CD19, one of the main membrane proteins of B lymphocytes, which is expressed in the maturation step ( Stüve et al, 2014 ), and CD200, which is expressed on neurons, oligodendrocytes and on reactive astrocytes ( Koning et al, 2009 ). Supplementary Figures S3G–I shows the mean percentages ± SD of CD200 + , CD19 + , and CD19 + /CD200 + CSF-EVs in the rMS, pMS, CIS, OIND, and ONIND groups.…”

Condition-dependent generation of aquaporin-4 antibodies from circulating B cells in neuromyelitis optica

“…In a disease characterized by AQP4-IgG production over years, sometimes decades ( Leite et al , 2012 ), this model may present a deviation from traditional paradigms of antibody production that implicate the non-proliferative, CD20-negative bone marrow-niched long-lived plasma cells as major secretors of long-lived serum antibodies ( Leite et al , 2012 ; Stüve et al , 2014 ; Alexander et al , 2015 ; Bennett et al , 2015 ; Halliley et al , 2015 ). Without direct sampling from this compartment, our study does not fully exclude a contribution from bone marrow-niched long-lived plasma cells.…”

Promise, Progress, and Pitfalls in the Search for Central Nervous System Biomarkers in Neuroimmunological Diseases: A Role for Cerebrospinal Fluid Immunophenotyping

“…102 Plasma cells are not targeted by anti-CD20. 103 The anti-CD19 monoclonal antibody, inebilizumab, has progressed to clinical trials for MS, NMO, and systemic sclerosis. 104 Possible risks include chronic B cell depletion.…”