Clinical Stabilization and Effective B-Lymphocyte Depletion in the Cerebrospinal Fluid and Peripheral Blood of a Patient With Fulminant Relapsing-Remitting Multiple Sclerosis

Abstract

Background: The anti-CD20 monoclonal antibody rituximab effectively depletes B lymphocytes and has been successfully used in the therapy of immune-mediated disorders of the peripheral nervous system. A limited effect of rituximab on B lymphocytes in the cerebrospinal fluid compartment of patients with primary progressive multiple sclerosis (MS) was recently reported. Objective: To determine the effect of rituximab on clinical, magnetic resonance imaging, and immunological variables in a patient with relapsing-remitting MS. Design: A patient with relapsing-remitting MS was treated with rituximab. The patient was repeatedly examined clinically and by magnetic resonance imaging. The frequency of peripheral blood and cerebrospinal fluid B lym-phocytes was assessed by flow cytometry before, during, and after rituximab therapy. Results: Rituximabmonotherapyresultedinsignificantclinical improvement. Inflammatory surrogate markers on magnetic resonance imaging were also reduced. B lymphocytes weredepletedinthecerebrospinalfluidandperipheralblood. Conclusions: Our data demonstrate beneficial clinical effects of rituximab in relapsing-remitting MS, mediated through modulation of humoral systemic and central nervous system intrinsic immune responses. Clinical trials should determine optimal therapeutic strategies for patients with relapsing-remitting MS.

Single-cell profiling indicates a high similarity between immune cells in the cerebrospinal fluid and in meningeal ectopic lymphoid tissue in experimental autoimmune encephalomyelitis

“…Possibly, this altered phenotype favors accumulation of those myeloid cells in the CSF. In line with our data, studies have demonstrated that B cell depletion by aCD20 mAbs like rituximab and ocrelizumab in MS patients led to a strong reduction of CSF B cells and, to a lesser degree, T cells ( 48 – 50 ). To our knowledge, no data regarding CSF macrophages in B cell depleted CSF has been published.…”

Single-cell profiling indicates a high similarity between immune cells in the cerebrospinal fluid and in meningeal ectopic lymphoid tissue in experimental autoimmune encephalomyelitis

“…Possibly, this altered phenotype favors accumulation of those myeloid cells in the CSF. In line with our data, studies have demonstrated that B cell depletion by aCD20 mAbs like rituximab and ocrelizumab in MS patients led to a strong reduction of CSF B cells and, to a lesser degree, T cells ( 48 – 50 ). To our knowledge, no data regarding CSF macrophages in B cell depleted CSF has been published.…”

Rituximab in a patient with multiple sclerosis - effect on B cells, plasma cells and intrathecal IgG synthesis

“…Our case illustrates the dramatic and sustained clinical improvement that can be achieved by treating autoimmune disease with rituximab. It confirms the findings in a similar case of rapidly progressing MS (7). In neuromyelitis optica, an antibody-mediated autoimmune disease of the spinal cord and the optic nerve with similarities to MS, a beneficial effect of rituximab has been documented as well (8).…”

B-cells and humoral immunity in multiple sclerosis. Implications for therapy

“…Unlike the results reported by Monson et al [70], B-cell levels in the CSF and peripheral blood were depleted in the patient with relapsing-remitting MS after the administration of rituximab. The patient also showed clinical and MRI improvement [71]. Similar data on B-cell depletion from the CSF after rituximab administration for 24 weeks have recently been published [72]; this new study also found that B-cell depletion was associated with a reduction in T-cells in the CSF [72].…”

Single-cell profiling indicates a high similarity between immune cells in the cerebrospinal fluid and in meningeal ectopic lymphoid tissue in experimental autoimmune encephalomyelitis

“…Possibly, this altered phenotype favors accumulation of those myeloid cells in the CSF. In line with our data, studies have demonstrated that B cell depletion by aCD20 mAbs like rituximab and ocrelizumab in MS patients led to a strong reduction of CSF B cells and, to a lesser degree, T cells ( 48 – 50 ). To our knowledge, no data regarding CSF macrophages in B cell depleted CSF has been published.…”

Rituximab in a patient with multiple sclerosis - effect on B cells, plasma cells and intrathecal IgG synthesis

“…Our case illustrates the dramatic and sustained clinical improvement that can be achieved by treating autoimmune disease with rituximab. It confirms the findings in a similar case of rapidly progressing MS (7). In neuromyelitis optica, an antibody-mediated autoimmune disease of the spinal cord and the optic nerve with similarities to MS, a beneficial effect of rituximab has been documented as well (8).…”

B-cells and humoral immunity in multiple sclerosis. Implications for therapy

“…Unlike the results reported by Monson et al [70], B-cell levels in the CSF and peripheral blood were depleted in the patient with relapsing-remitting MS after the administration of rituximab. The patient also showed clinical and MRI improvement [71]. Similar data on B-cell depletion from the CSF after rituximab administration for 24 weeks have recently been published [72]; this new study also found that B-cell depletion was associated with a reduction in T-cells in the CSF [72].…”

Single-cell profiling indicates a high similarity between immune cells in the cerebrospinal fluid and in meningeal ectopic lymphoid tissue in experimental autoimmune encephalomyelitis

“…Possibly, this altered phenotype favors accumulation of those myeloid cells in the CSF. In line with our data, studies have demonstrated that B cell depletion by aCD20 mAbs like rituximab and ocrelizumab in MS patients led to a strong reduction of CSF B cells and, to a lesser degree, T cells ( 48 – 50 ). To our knowledge, no data regarding CSF macrophages in B cell depleted CSF has been published.…”

Rituximab in a patient with multiple sclerosis - effect on B cells, plasma cells and intrathecal IgG synthesis

“…Our case illustrates the dramatic and sustained clinical improvement that can be achieved by treating autoimmune disease with rituximab. It confirms the findings in a similar case of rapidly progressing MS (7). In neuromyelitis optica, an antibody-mediated autoimmune disease of the spinal cord and the optic nerve with similarities to MS, a beneficial effect of rituximab has been documented as well (8).…”

B-cells and humoral immunity in multiple sclerosis. Implications for therapy

“…Unlike the results reported by Monson et al [70], B-cell levels in the CSF and peripheral blood were depleted in the patient with relapsing-remitting MS after the administration of rituximab. The patient also showed clinical and MRI improvement [71]. Similar data on B-cell depletion from the CSF after rituximab administration for 24 weeks have recently been published [72]; this new study also found that B-cell depletion was associated with a reduction in T-cells in the CSF [72].…”