Immunoadsorption therapy in autoimmune encephalitides

Onugoren, Müjgan Dogan; Golombeck, Kristin S.; Bien, Corinna I.; Abu-Tair, M.; Brand, Marcus; Bulla-Hellwig, Michael; Lohmann, Hubertus; Münstermann, Dieter; Pavenstädt, Hermann; Thölking, Gerold; Valentin, Rainer; Wiendl, Heinz; Melzer, Nico; Bien, Christian G.

doi:10.1212/nxi.0000000000000207

Cited by 84 publications

(72 citation statements)

References 38 publications

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“…Given the direct pathogenetic role of NMDAR-Abs, the use of apheresis therapy is very reasonable. The efficacy of immunoadsorption seems to be similar to those of plasma exchange [47,48]. As expected, an early immunotherapy ( < 40 days after initial manifestation) is associated with a significantly better prognosis [43].…”

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confidence: 67%

Management of Immune-Mediated Paraneoplastic Neurological Disorders

Ayzenberg

Gold

Kleiter

2017

Neurology International Open

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AbsTR Ac TParaneoplastic neurological disorders are rare and clinically heterogeneous diseases. They can affect both the central and peripheral nervous system as well as the neuromuscular junction and muscle. Neurological deficits develop in 2/3 of cases prior to cancer diagnosis. The diagnostic approach includes screening for antineuronal antibodies and a search for the underlying tumor. A prompt tumor therapy in combination with immunotherapy is the cornerstone in the management of these diseases. Due to lack of clinical trials, treatment recommendations are based on case series and expert opinions. Highdose corticosteroids, intravenous immunoglobulins and apheresis therapies are often used in the acute stage of the disease. These therapies should be started as early as possible, e. g., during tumor screening, in order to prevent irreversible damage. Long-term treatment is mostly immunosuppressive and depends on the specific paraneoplastic syndrome. Outcomes vary depending upon the prognosis of the underlying cancer and the nature of the antineuronal antibodies. Disorders with antibodies directed against antigens on the neuronal cell surface are highly sensitive to B cell-directed therapies and mostly associated with a favorable outcome. A thorough review of published data on actual treatment recommendation is provided along with discussion of currently not validated, but potentially effective new therapies. E264Ayzenberg I et al. Management of Immune-mediated Paraneoplastic … Neurology International Open 2017; 1: E264-E274 course, treatment response and prognosis of PNS [2,3]. Depending on tumor association, obligate and facultative paraneoplastic Abs are differentiated (Tab. 1).Clinically, the following PNS exist [3,4]: A. In the central nervous system: ▪ Encephalomyelitis (incl. brainstem encephalitis) ▪ Limbic encephalitis ▪ Subacute cerebellar degeneration ▪ Opsoclonus-myoclonus syndrome ▪ Optic neuritis/neuromyelitis optica ▪ Myelopathy/myelitis ▪ Stiff person syndrome ▶Table 1 Paraneoplastic antibodies: associated neurological syndromes and tumors. Target antigen clinical presentation# Association with tumorObligate paraneoplastic Abs (directed against intracellular antigens; tumor association > 95 %) In this review we discuss the diagnosis and management of PNS. With regard to facultative paraneoplastic syndromes which are more frequently of autoimmune origin, such as neuromyelitis optica or myasthenia gravis, the reader should refer to pertinent reviews [5,6]. Diagnostic and Pathogenetic Significance of Antibodies to Intracellular and Surface AntigensAntibodies (Abs) to intracellular antigens or so-called "classical" Abs are almost always tumor-associated (exception: GAD-Abs). They can be associated with various tumors and a variety of neurological conditions [7]. However, a direct pathogenetic significance of these Abs has not yet been demonstrated. Abs to intracellular antigens serve as useful diagnostic markers in the targeted tumor search in PNS. Here, cell-mediated immune responses play a major p...

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supporting

confidence: 67%

Management of Immune-Mediated Paraneoplastic Neurological Disorders

Ayzenberg

Gold

Kleiter

2017

Neurology International Open

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“…Clinical trials using tryptophan IA showed rapid response of neurologic symptoms being refractory to drugbased strategies, for example, in patients with myasthenic crisis [22,23] . In autoimmune encephalitides, IA led to improvement in up to 86% of patients with antibodies directed to CNS surface antigens [24,25] . Reduction of serum antibodies with IA also resulted in the reduction of antibodies in CSF.…”

Section: Discussionmentioning

confidence: 99%

“…Three major mechanisms of action for IA in autoantibody-mediated neurological diseases act together: immediate intravascular reduction of antibody and immune complex concentration, pulsed induction of antibody redistribution, and subsequent immunomodulatory changes [25,27] . The mechanism of the effectiveness of IA for MS is not yet fully understood.…”

Section: Discussionmentioning

confidence: 99%

Escalation Therapy of Steroid Refractory Multiple Sclerosis Relapse with Tryptophan Immunoadsorption - Observational Multicenter Study with 147 Patients

et al. 2016

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Background: A marked proportion of multiple sclerosis (MS) relapses is followed by incomplete recovery. Our aim was to considerably increase the evidence of the clinical use of immunoadsorption (IA) as escalation therapy for patients with MS relapse. Methods: A retrospective multicenter study was performed in MS patients with steroid refractory relapse who were treated with tryptophan IA. The main outcome parameter was change of acute relapse-related disability assessed by Expanded Disability Status Scale (EDSS) and visual acuity (VA) measurements for patients with optic neuritis (ON). IA treatments were performed using single-use tryptophan adsorbers. Results: Data of 147 MS patients and 786 single IA treatments were analyzed. Treatment with IA was commenced in mean 32 ± 35 days after the onset of relapse. One hundred and five out of 147 patients (71.4%) improved functionally after mean 5.4 IA treatments within 7-10 days. EDSS improved from median 5 (interquartile range, IQR 3.5) to 4 (IQR 2.5) (p < 0.001). In patients with ON (n = 32), VA improved after the IA series in 84% of cases from median 0.2 (IQR 0.6) to 0.6 (IQR 0.66) (p < 0.001). In 98.9% of IA treatments, no clinically relevant side effect was reported. Conclusion: Tryptophan IA was found to be effective and well tolerated as escalation therapy for MS relapse.

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“…These observations, coupled with the highly heterogeneous phenotypes of patients with NMDAR antibodies in serum but not CSF, may suggest that the predicted natural diffusion of NMDAR‐IgG into the CNS is insufficient to generate this encephalitis phenotype. Yet, maybe the soluble autoantibodies do play a role in ongoing disease as plasma immunoabsorption of IgG leads to a fall in CSF autoantibodies and correlates with improvements in clinical status . The relative contributions of serum autoantibody transfer into the CNS and the degree of immune cell infiltration may vary across diseases but also within diseases, and could determine the likelihood of amelioration with plasma exchange or predict the need for future intrathecal‐directed therapies.…”

Section: The Therapeutically Relevant Immunologymentioning

confidence: 99%

The clinical features, underlying immunology, and treatment of autoantibody‐mediated movement disorders

et al. 2018

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An increasing number of movement disorders are associated with autoantibodies. Many of these autoantibodies target the extracellular domain of neuronal surface proteins and associate with highly specific phenotypes, suggesting they have pathogenic potential. Below, we describe the phenotypes associated with some of these commoner autoantibody‐mediated movement disorders, and outline increasingly well‐established mechanisms of autoantibody pathogenicity which include antigen downregulation and complement fixation. Despite these advances, and the increasingly robust evidence for improved clinical outcomes with early escalation of immunotherapies, the underlying cellular immunology of these conditions has received little attention. Therefore, here, we outline the likely roles of T cells and B cells in the generation of autoantibodies, and reflect on how these may guide both current immunotherapy regimes and our future understanding of precision medicine in the field. In addition, we summarise potential mechanisms by which these peripherally‐driven immune responses may reach the central nervous system. We integrate this with the immunologically‐relevant clinical observations of preceding infections, tumours and human leucocyte antigen‐associations to provide an overview of the therapeutically‐relevant underlying adaptive immunology in the autoantibody‐mediated movement disorders. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Immunoadsorption therapy in autoimmune encephalitides

Cited by 84 publications

References 38 publications

Management of Immune-Mediated Paraneoplastic Neurological Disorders

Management of Immune-Mediated Paraneoplastic Neurological Disorders

Escalation Therapy of Steroid Refractory Multiple Sclerosis Relapse with Tryptophan Immunoadsorption - Observational Multicenter Study with 147 Patients

The clinical features, underlying immunology, and treatment of autoantibody‐mediated movement disorders

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