Serum peptide reactivities may distinguish neuromyelitis optica subgroups and multiple sclerosis

Abstract

Objective:To assess in an observational study whether serum peptide antibody reactivities may distinguish aquaporin-4 (AQP4) antibody (Ab)–positive and -negative neuromyelitis optica spectrum disorders (NMOSD) and relapsing-remitting multiple sclerosis (RRMS).Methods:We screened 8,700 peptides that included human and viral antigens of potential relevance for inflammatory demyelinating diseases and random peptides with pooled sera from different patient groups and healthy controls to set up a customized microarray with 700 peptides. With this microarray, we tested sera from 66 patients with AQP4-Ab-positive (n = 16) and AQP4-Ab-negative (n = 19) NMOSD, RRMS (n = 11), and healthy controls (n = 20).Results:Differential peptide reactivities distinguished NMOSD subgroups from RRMS in 80% of patients. However, the 2 NMOSD subgroups were not well-discriminated, although those patients are clearly separated by their antibody reactivities against AQP4 in cell-based assays. Elevated reactivities to myelin and Epstein-Barr virus peptides were present in RRMS and to AQP4 and AQP1 peptides in AQP4-Ab-positive NMOSD.Conclusions:While AQP4-Ab-positive and -negative NMOSD subgroups are not well-discriminated by peptide antibody reactivities, our findings suggest that peptide antibody reactivities may have the potential to distinguish between both NMOSD subgroups and MS. Future studies should thus concentrate on evaluating peptide antibody reactivities for the differentiation of AQP4-Ab-negative NMOSD and MS.

Aquaporins in the Spinal Cord

“…Autoantibodies against AQP1 (AQP1-Abs) were found among patients in the high risk group (characterized by presence of AQP4 autoantibodies with early forms of LETM or optic neuritis [70]) and diagnosed with NMO and/or MS [71,72,73]. Interestingly, patients with sero-positivity for AQP4-IgG belonging to the NMOsd group had higher reactivity to AQP1 peptides compared to the NMOsd group with AQP4-IgG sero-negativity [71,74]. AQP1-Abs found among NMOsd patients belong to the complement-activating IgG1 subclass that possesses affinity for the extracellular domain of AQP1 [72].…”

Longitudinal Intravital Imaging of the Retina Reveals Long-term Dynamics of Immune Infiltration and Its Effects on the Glial Network in Experimental Autoimmune Uveoretinitis, without Evident Signs of Neuronal Dysfunction in the Ganglion Cell Layer

“…Frequently, the very first clinical signs of MS disease course are related to transient loss of vision (1–3). In the case of neuromyelitis optica (NMO), another chronic neuroinflammatory disease with strong involvement of the retina, permanent damage of visual function represents a clinical hallmark (4–6). Thinning of the neuronal retina, i.e., retinal neural fiber layer and the ganglion cell layer (GCL), has been demonstrated using optical coherence tomography (OCT) both in MS and NMO patients (7, 8).…”

Multiple Autoantibodies and Neuromyelitis Optica Spectrum Disorders

“…Neuromyelitis optica spectrum disorder (NMOSD) is an immune-mediated inflammatory disease of the central nervous system [1,2]. Recent studies have shown that the anti-aquaporin 4 antibody (AQP4-Ab), present in >80% of patients with NMOSD [3,4], causes astrocyte damage, inflammatory cell infiltration and myelin loss [5].…”