Immunoadsorption and Plasma Exchange in Seropositive and Seronegative Immune-Mediated Neuropathies

Abstract

<jats:p>The inflammatory neuropathies are disabling conditions with diverse immunological mechanisms. In some, a pathogenic role for immunoglobulin G (IgG)-class autoantibodies is increasingly appreciated, and immunoadsorption (IA) may therefore be a useful therapeutic option. We reviewed the use of and response to IA or plasma exchange (PLEx) in a cohort of 41 patients with nodal/paranodal antibodies identified from a total of 573 individuals with suspected inflammatory neuropathies during the course of routine diagnostic testing (PNAb cohort). 20 patients had been treated with PLEx and 4 with IA. Following a global but subjective evaluation by their treating clinicians, none of these patients were judged to have had a good response to either of these treatment modalities. Sequential serology of one PNAb+ case suggests prolonged suppression of antibody levels with frequent apheresis cycles or adjuvant therapies, may be required for effective treatment. We further retrospectively evaluated the serological status of 40 patients with either Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP), and a control group of 20 patients with clinically-isolated syndrome/multiple sclerosis (CIS/MS), who had all been treated with IgG-depleting IA (IA cohort). 32 of these patients (8/20 with CIDP, 13/20 with GBS, 11/20 with MS) were judged responsive to apheresis despite none of the serum samples from this cohort testing positive for IgG antibodies against glycolipids or nodal/paranodal cell-adhesion molecules. Although negative on antigen specific assays, three patients’ pre-treatment sera and eluates were reactive against different components of myelinating co-cultures. In summary, preliminary evidence suggests that GBS/CIDP patients without detectable IgG antibodies on routine diagnostic tests may nevertheless benefit from IA, and that an unbiased screening approach using myelinating co-cultures may assist in the detection of further autoantibodies which remain to be identified in such patients.</jats:p>

Safety and Tolerability of Plasma Exchange and Immunoadsorption in Neuroinflammatory Diseases

“…For other indications, no systematic evaluation of efficacy was done due to low numbers of patients. Efficacy data refer to subgroups of patients with sufficient clinical data and have been published previously [5,20,22].…”

“…A retrospective analysis of 20 patients with GBS [22] yielded response rates of 61.5% for IA and 71.4% for PE after the last treatment based on the documented neurological examinations.…”

IgG1 pan-neurofascin antibodies identify a severe yet treatable neuropathy with a high mortality

“…From July 2017 to May 2020, we tested serum samples from 649 patients with suspected inflammatory neuropathies for IgG antibodies directed against nodal (neurofascin-186) and paranodal (neurofascin-155, contactin-1 and contactin-associated protein, Caspr1) cell-adhesion molecules, using a live, cell-based assay. [12] A standardised request form was used to collect clinical data. This study was approved by the NHS National Research Ethics Service Committee (South Central – Oxford A, 14/SC/0280).…”

“…[6] Recently, antibodies directed against nodal/paranodal proteins have been identified in atypical forms of CIDP. [4,7–12]…”

Apheresis in Neurological Disorders

“…Although to date distinct disease-related antibodies are not detected in the majority of patients, the discovery of potential pathogenic auto-antibodies against proteins of the node of Ranvier and paranodal regions [ 12 ] have corroborated the importance of auto-antibodies in at least a subgroup of patients with immune-mediated neuropathies and therefore supported the rationale to apply treatments which target these antibodies. Alexander Davies and colleagues [ 13 ] investigated whether the existence of such antibodies may predict the response to apheresis in patients with GBS and CIDP. Interestingly, they did not find a clear correlation between the presence of known auto-antibodies and treatment response, suggesting that further, undiscovered antibodies may be present.…”