Dynamic Changes in AQP4-IgG Level and Immunological Markers During Protein-A Immunoadsorption Therapy for NMOSD: A Case Report and Literature Review

Abstract

The changes in the serum levels of aquaporin-4-IgG (AQP4-IgG), immunoglobulins, and inflammatory mediators in neuromyelitis optica spectrum disorder (NMOSD) cases treated with immunoadsorption have been rarely described in detail. Here we report a 29-year-old steroid-resistant NMOSD female with a severe disability (bilateral blindness and paraplegia) who received protein-A immunoadsorption as a rescue treatment. During the total 5 sessions, the circulating level of AQP4-IgG, immunoglobulins, and complement proteins (C3 and C4) showed a rapid and sawtooth-like decrease, and the serum AQP4-IgG titer declined from 1:320 to below the detectable limit at the end of the 3rd procedure. Of all the antibodies, IgG had the biggest removal rate (>96.1%), followed by IgM (>66.7%) and IgA (53%), while complement C3 and C4 also dropped by 73% and 65%, respectively. The reduced pro-inflammatory cytokines (interleukin-8 and tumor necrosis factor-α) and marked increased lymphocyte (T and B cell) counts were also observed. The improvement of symptoms initiated after the last session, with a low AQP4-IgG titer (1:32) persisting thereafter. Accordingly, protein-A immunoadsorption treatment could be one of the potential rescue therapies for steroid-resistant NMOSD patients with a severe disability.

Efficacy and safety of apheresis therapy in AQP4 antibody‐positive NMOSD attack: A propensity score‐matched cohort study

“…This may be related to the mechanism of PE/IA: quickly clear serum AQP4-IgG and complement, reduce the damage of astrocytes caused by membrane attack complex; and regulate lymphocyte subsets and cytokines to reduce disease activity. 7 We found prognostic factors after acute episodes of NMOSD PE and IA constitute safety therapeutic options in NMOSD acute attacks. We recorded two patients (6.45%) in the PE group with transient hypotension, which recovered quickly after rehydration therapy.…”

“…5 Apheresis therapies, which include the two main therapies plasma exchange (PE) and immunoadsorption (IA), aim to eliminate disease-causing antibodies and other pro-inflammatory factors from the patient's peripheral circulation. [6][7][8] Although PE/IA + IVMP treatment was found to be effective in previous retrospective studies, high-quality evidence was lacking. [9][10][11][12][13] Randomized placebo-controlled trials of PE/IA + IVMP treatment are necessary to provide high-quality evidence.…”

Factors influencing the cerebrospinal fluid antibodies to aquaporin-4: a study of 87 patients with neuromyelitis optica spectrum disorder

“…As some therapies such as immunoadsorption decrease AQP4-IgG titer obviously, the therapy heterogeneity may interference our results [22].…”

APOE from patient-derived astrocytic extracellular vesicles alleviates neuromyelitis optica spectrum disorder in a mouse model

“…DEGs with the P value adjusted by Benjamini-Hochberg < 0.05 were considered significant. KEGG pathway enrichment analysis was performed by gseKEGG function in clusterProfiler (v4.6.2) ( 55 ). Wilcoxon rank-sum test continuity correction was used for comparisons of gene expression.…”

“…NMOSD-IgG isolation and preparation of the hC NMOSD-IgG was purified from plasma immune adsorption columns (IMMUSORBA TR-350) (55) from two patients affected by NMOSD and showed the presence of AQP4-Abs. The anti-AQP4 Abs testing was performed by the Euroimmun Medical Diagnostic Laboratory (China) using a fixed cell-based indirect immunofluorescence test into BIOCHIPs (EUROIMMUN AG, Lübeck, Germany), and the results were confirmed by ELISA.…”