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

Disclosures

J Neuroinflammation. 2012;9(80) 

In This Article

Background

Previous studies have described four immunopathological patterns of demyelination in early multiple sclerosis (MS) lesions, with pattern II being characterized by antibody and/or complement-associated demyelination.[1] Several specific antibodies have been described and discussed to contribute to the humoral autoimmune response in MS.[2] Immunoglobulins are synthesized intrathecally; however, at least part of the humoral response in MS is derived systemically from the blood.[3]

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] The usefulness of PE has also been extended to severe optic neuritis in patients with MS.[5,6] Thus, the use of PE in steroid-refractory relapses has become an integral part of European guidelines for the treatment of MS.[7] 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.

Immunoadsorption (IA) provides a more selective approach and the potential for technical innovations in therapeutic apheresis techniques, allowing the elimination of pathogenic antibodies while sparing other plasma proteins. With IA, relevant side effects of PE resulting from protein substitution can be avoided.[9] We hypothesized that IA is at least equally efficient compared to PE as an escalation therapy for steroid-unresponsive relapses of MS. Therefore, we performed a prospective trial to compare IA treatment in 11 patients with MS with our earlier patient population treated with PE for their MS.[10] In addition, proteomic analyses of column-bound proteins were performed as well as measurements of corresponding changes in patients' plasma samples.

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