Klaus Lehmann‐Horn

Learn More
OBJECTIVE Clinical studies indicate that anti-CD20 B-cell depletion may be an effective multiple sclerosis (MS) therapy. We investigated mechanisms of anti-CD20-mediated immune modulation using 2 paradigms of experimental autoimmune encephalomyelitis (EAE). METHODS Murine EAE was induced by recombinant myelin oligodendrocyte glycoprotein (rMOG), a model(More)
Mutations in the gene encoding the E3 ubiquitin-protein ligase parkin have been shown to be a common genetic cause of familial early-onset Parkinson's disease (PD). In addition to its function in the ubiquitin-proteasome system (UPS), parkin has been ascribed general neuroprotective properties. Stress and mutation induced decreases in parkin solubility(More)
Recent years have substantially broadened our view on the pathogenesis of multiple sclerosis (MS). While earlier concepts focused predominantly on T lymphocytes as the key cell type to mediate inflammatory damage within central nervous system (CNS) lesions, emerging evidence suggests that B lymphocytes may play a comparably important role both as precursors(More)
Natalizumab, which binds very late antigen-4 (VLA-4), is a potent therapy for multiple sclerosis (MS). Studies have focused primarily upon its capacity to interfere with T-cell migration into the central nervous system (CNS). B cells are important in MS pathogenesis and express high levels of VLA-4. Here, we report that the selective inhibition of VLA-4(More)
Clinical trials revealed that systemic administration of B-cell-depleting anti-CD20 antibodies can hold lesion formation in the early relapsing-remitting phase of multiple sclerosis (MS). Throughout the secondary-progressive (SP) course of MS, pathogenic B cells may, however, progressively replicate within the central nervous system (CNS) itself, which is(More)
OBJECTIVE To evaluate the influence of dimethyl fumarate (DMF, Tecfidera) treatment of multiple sclerosis (MS) on leukocyte and lymphocyte subsets. METHODS Peripheral blood leukocyte and lymphocyte subsets, including CD3(+), CD4(+), and CD8(+) T cells; CD19(+) B cells; and CD56(+) natural killer (NK) cells, were obtained at baseline and monitored at 3(More)
BACKGROUND Clinical trials evaluating anti-CD20-mediated B-cell depletion in multiple sclerosis (MS) and neuromyelitis optica (NMO) generated encouraging results. Our recent studies in the MS model experimental autoimmune encephalomyelitis (EAE) attributed clinical benefit to extinction of activated B-cells, but cautioned that depletion of naïve B-cells may(More)
Bacterial and viral infections have long been implicated in pathogenesis and progression of multiple sclerosis (MS). Incidence and severity of its animal model experimental autoimmune encephalomyelitis (EAE) can be enhanced by concomitant administration of pertussis toxin (PTx), the major virulence factor of Bordetella pertussis. Its adjuvant effect at the(More)
BACKGROUND Collectively, research on the role of B-cells in the pathogenesis of multiple sclerosis (MS) illustrates how translational medicine has given rise to promising therapeutic approaches for one of the most debilitating chronic neurological diseases in young adults. First described in 1935, the experimental autoimmune/allergic encephalomyelitis model(More)
OBJECTIVE To investigate the role of very late antigen-4 (VLA-4) on regulatory B cells (Breg) in CNS autoimmune disease. METHODS Experimental autoimmune encephalomyelitis (EAE) was induced in mice selectively deficient for VLA-4 on B cells (CD19cre/α4(f/f)) by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide (p)35-55 or recombinant(More)