Nowadays, therapeutic plasma exchange (PE) is the most common apheresis procedure. Plasma is separated from corpuscular blood constitutents and replaced with a substitution fluid. Thus, PE is a non-specific treatment modality. Its therapeutic effect is based on the removal of circulating, pathogenic immune factors, including autoantibodies. To date, PE is well established for several immune mediated neurological disorders. Whilst the first experience was acquired in acute life-threatening conditions, such as the treatment of Guillain–Barré syndrome or myasthenic crisis, therapeutic success was later achieved in other chronic autoimmune diseases; PE was applied successfully in chronic inflammatory demyelinating polyneuropathy, paraproteinaemic polyneuropathy, stiff-person syndrome and might also be tried in autoimmune diseases of paraneoplastic origin. From a novel aspect, PE was also established as an escalation therapy for steroid unresponsive relapses of multiple sclerosis, and thus has gained even more widespread attention. Humoral disease mechanisms dominate even more in neuromyelitis optica, as a subtype of MS, and usually respond to PE. Adding to its increasing application in clinical practice, the procedure is usually well tolerated. Possible adverse reactions of PE arise from the large-size vascular access site, the use of replacement fluids and the need for anticoagulation.
Although plasmapheresis has been established as effective in many autoimmune disorders, there are still issues to be addressed over the coming years. Immunological investigations and experimental studies should further clarify the mechanisms of PE action. Although the elimination of antibodies is a conceivable mechanism of action, these factors also influence cellular crosstalk. Thus, the modulation of cellular immune responses after elimination of humoral factors needs to be characterized in more detail. Here, Fc receptor bearing cells, including macrophages and NK cells, are in the centre of interest.
Further trials on the value of immunoadsorption are urgently needed, which might be of special interest as escalation therapy for MS relapses. Whereas in myasthenia gravis, some data support the superiority of immunoadsorption regimes as compared with conventional plasma exchange, the value of immunoadsorption in other autoimmune diseases is less clear. Randomized and double-blind head-to-head studies are warranted to prove equivalence of immunoadsorption to therapeutic plasma exchange. So far, the USA clinical trial registry (http://www.clinicaltrials.gov) only lists one study testing the value of plasma exchange for the elimination of natalizumab in MS patients. Even here, when comparing individual case reports, immunoadsorption may be superior.62,63
Finally, some retrospective studies already evaluate appropriate long-term follow-up therapies after plasma exchange in MS patients. From these data, it is clear that the need for plasma exchange in MS relapses should coincide with the initiation of a disease modifying therapy. Alternatively, an existing long-term therapy should be critically re-evaluated for the need of therapy escalation. In particular, immunotherapies targeting B cells or plasma cells as the source of pathogenic antibodies are of special interest as follow-up therapies. Although mitoxantrone might lead to B cell apoptosis,64 the B cell depleting anti-CD20 monoclonal antibody showed some very promising effects on MRI markers of disease in two recently published phase II studies65,66
As the ultimate goal, the development of suitable biomarkers for PE responders requires special attention. Here, proteomic profiling of sera and eventually also CSF from MS patients might help to identify suitable markers that need to be tested in clinical practice.
soure: clinical and experimental neuro immunology
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