Immunoadsorption Therapy in Patients With Multiple Sclerosis With Steroid-Refractory Optical Neuritis

Michael J Koziolek; Desiree Tampe; Matthias Bühr; Hassan Dihazi; Klaus Jung; Dirk Fitzner; Reinhard Klinge; Gerhard A Müller; Bernd Kitze


J Neuroinflammation. 2012;9(80) 

In This Article


PE is an efficient treatment in acute central nervous system inflammatory demyelinating diseases,[4] including severe optic neuritis, motor impairment or ataxia[5,6] after steroid-refractory relapses, successful in about 40% to 50% of cases. Here, we report on the first prospective investigation of tryptophan-IA in 11 relapsing MS patients with optic neuritis refractory to corticosteroid pulses in an open prospective study. Overall, eight of eleven patients (72.7%) achieved a remission. One patient gradually improved but deteriorated again along with the development of jugular venous thrombosis, and two patients did not respond at all. The response to IA seems to be comparable to the best results achieved in PE series[5,6] and to two very recent retrospective analyses of the effect of IA in steroid-refractory MS cases.[18,19] As in our own PE study,[10] significant clinical improvement was seen after the third extracorporeal treatment session with a trend in favor of early IA initiation compared to delayed IA initiation. Our treatment protocol was limited to a total of five IA sessions. Additional experience showed that increasing the number of apheresis sessions did not correlate with further improvement of outcome (data not shown). This observation is in accord with results of IA in acute autoimmune neuropathies like Guillain-Barré Syndrome.[20]

Most side effects were typical of any apheresis procedure using central venous lines as vascular access, but not characteristic of IA. Compared with the safety data from previously published PE studies,[15,21] the incidence of mild adverse events was higher in our study, and moderate side effects were slightly more frequent. However, moderate side effects were almost level with our own study of neurological patients treated with PE.[15] Potential side effects of PE known to be related to the substitution of human plasma products were completely avoided.[12]

Apart from clinical data, we analyzed possible therapeutic effects of IA with the help of proteomic analyses. Several relevant proteins, particularly fibrinogen and the immunoglobulins, were monitored. The decrease of fibrinogen is one limiting factor in the use of tryptophan-IA that makes regular controls necessary. Our protocol with five IA sessions on alternate days did not decrease fibrinogen to critical levels. Moreover, immunoglobulin depletion along with prior corticosteroid pulse therapy reflects a strong immunosuppression, which makes close controls of clinical and laboratory infection signs necessary. Previous investigations reported that the restoration of serum IgG levels until day 5 after IA does not result from increased antibody synthesis, but is probably related to changes of catabolism and immunoglobulin backflow.[7] Interestingly enough, we found a significant immunoglobulin increase beyond baseline values until day 180 ± 10 after the start of IA, suggesting additional mechanisms other than backflow alone.

Several mechanisms of PE action in neuroimmunological disorders have been described, such as a removal of pathogenic autoantibodies, a redistribution of pathogens from the extravascular to the intravascular compartment, increased proliferation of immune cells, an enhanced production of immunoglobulins, a promotion of suppressor T-cell function, and a deviation of cytokine patterns redressing a disturbed T-helper type 1 and T-helper type 2 balance.[3] Although IA has been termed specific, several studies have demonstrated additional binding properties of ligands other than immunoglobulins alone.[22,23] According to our proteomics data, several proteins that are possibly involved in MS pathogenesis are removed from the plasma by IA, for example, transthyretin,[24] serum amyloid P,[24] complement factors,[24] clusterin,[24] gelsolin,[24] kininogen-1,[24] MBP,[25,26] CD5L[27] and immunoglobulins.[1,3,8] We confirmed a decrease of serum levels by IA in two of them, MBP and sCD5L. MBP-like material has been detected in several body fluids including cerebral spinal fluid and the urine of patients with MS.[28] Since MBP and other myelin proteins have been shown to be encephalitogenic in animal models of MS, they could drive the systemic autoimmune response in patients with MS. Other investigations have demonstrated the prevalence of MBP-specific memory B-cells in the peripheral blood of relapsing patients with remitting MS that might prime T-cells in lymphoid organs to migrate into the central nervous system and to elicit IFN-γ secretion.[25] These data were further corroborated with the evidence of MBP-reactive T-cells among IL-2 expanded lymphocytes in patients with MS.[26] Thus, removal of MBP from the plasma by IA might interrupt these autoimmune mechanisms, although more research in this hypothesis is definitely needed.

sIL-2R, a marker of TH1 cell activation, is increased in the serum of patients with relapsing MS.[14] We induced a significant decrease of sIL-2R after IA in responders, but not in non-responders. Decreased sIL-2R levels might reflect the silencing of cellular autoimmune responses effective only in responders.


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