Abstract
BackgroundIn multiple sclerosis relapses refractory to intravenous corticosteroid therapy, plasma exchange is recommended. Immunoadsorption (IA) is regarded as an alternative therapy, but its efficacy and putative mechanism of action still needs to be established.MethodsWe prospectively treated 11 patients with multiple sclerosis who had optical neuritis and fulfilled the indications for apheresis therapy (Trial registration DE/CA25/00007080-00). In total, five IA treatments were performed using tryptophan-IA. Clinical activity (visual acuity, Expanded Disability Status Scale, Incapacity Status Scale), laboratory values and visual evoked potentials were measured before, during and after IA, with a follow-up of six months. Moreover, proteomic analyses were performed to analyze column-bound proteins as well as corresponding changes in patients’ sera.ResultsAfter the third IA, we detected an improvement of vision in eight of eleven patients, whom we termed responders. Amongst these, the mean visual acuity improved from 0.15 ± 0.12 at baseline to 0.47 ± 0.32 after the third IA (P = 0.0252) up to 0.89 ± 0.15 (P < 0.0001) at day 180 ± 10 after IA. Soluble interleukin-2 receptor decreased in responders (P = 0.03), whereas in non-responders it did not. Proteomic analyses of proteins adsorbed to IA columns revealed that several significant immunological proteins as well as central nervous system protein fragments, including myelin basic protein, had been removed by IA.ConclusionsIA was effective in the treatment of corticosteroid-refractory optic neuritis. IA influenced the humoral immune response. Strikingly, however, we found strong evidence that demyelination products and immunological mediators were also cleared from plasma by IA.
Highlights
In multiple sclerosis relapses refractory to intravenous corticosteroid therapy, plasma exchange is recommended
IA treatments were started after a mean time of 26.6 days after the initial symptoms and 10.8 days after the start of corticosteroid therapy
Two patients did not respond to therapy at any time point and one patient improved during IA therapy but deteriorated shortly after the end of IA therapy, associated with the incidence of a jugular venous thrombosis on the same side
Summary
In multiple sclerosis relapses refractory to intravenous corticosteroid therapy, plasma exchange is recommended. Immunoglobulins are synthesized intrathecally; Therapeutic plasma exchange (PE) is based on the separation of plasma from cellular blood components, allowing the removal of substances up to a molecular weight of 3 × 103 kDa. As shown in a randomized placebo controlled cross-over study, PE was efficient for steroid - refractory relapses in about 40% to 50% of cases of acute central nervous system inflammatory demyelinating diseases [4]. Clinical-pathological correlation analyses have shown that all patients with pattern II pathology but none with pattern I or pattern III experienced improvement in neurological deficits after being treated with PE [8]. This selective response suggests a removal of pathogenic humoral and plasma factors by PE
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