Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Tuller, F; Holzer, H; Schanda, K; Aboulenein-Djamshidian, F; Höftberger, R; Khalil, M; Seifert-Held, T; Leutmezer, F; Berger, T; Reindl, M.
Characterization of the binding pattern of human aquaporin-4 autoantibodies in patients with neuromyelitis optica spectrum disorders.
J Neuroinflammation. 2016; 13(1):176-176 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Khalil Michael
Seifert-Held Thomas
Altmetrics:

Dimensions Citations:

Plum Analytics:
Number of Figures: 5
| | | | |
Abstract:
The discovery of a highly specific antibody against the aquaporin-4 (AQP4) water channel (AQP4-IgG) unified the spectrum of neuromyelitis optica spectrum disorders (NMOSD), which are considered to be antibody-mediated autoimmune diseases. The AQP4 water channel is located on astrocytic end-feet processes and consists of six transmembrane helical domains forming three extracellular loops A, C, and E in which defined amino acids were already proven to be critical for AQP4-IgG binding. However, the clinical relevance of these findings is unclear. Therefore, we have characterized the epitope specificity of AQP4-IgG-positive NMOSD patients. We established a cell-based flow cytometry assay for the quantitative detection of AQP4-IgG-positive serum samples. Human embryonic kidney (HEK) cells were transiently transfected with an EmGFP-tagged AQP4-M23, AQP4-M1, or six AQP4-M23 extracellular loop mutants including two mutations in loop A (serial AA substitution, insertion of a myc-tag), two in loop C (N153Q, insertion of a myc-tag), and two in loop E (H230G, insertion of a myc-tag). Fourty-seven baseline and 49 follow-up serum samples and six paired cerebrospinal fluid (CSF) baseline samples of 47 AQP4-IgG-positive Austrian NMOSD patients were then tested for their binding capability to AQP4-M1 and AQP4-M23 isoforms and these six extracellular loop mutants. Overall, we could identify two broad patterns of antibody recognition based on differential sensitivity to mutations in extracellular loop A. Pattern A was characterized by reduced binding to the two mutations in loop A, whereas pattern B had only partial or no reduced binding to these mutations. These two patterns were not associated with significant differences in demographic and clinical parameters or serum titers in this retrospective study. Interestingly, we found a change of AQP4-IgG epitope recognition pattern in seven of 20 NMOSD patients with available follow-up samples. Moreover, we found different binding patterns in five of six paired CSF versus serum samples, with a predominance of pattern A in CSF. Our study demonstrates that AQP4-IgG in sera of NMOSD patients show distinct patterns of antibody recognition. The clinical and diagnostic relevance of these findings have to be addressed in prospective studies.
Find related publications in this database (using NLM MeSH Indexing)
Adult -
Aged -
Aquaporin 4 - chemistry
Aquaporin 4 - genetics
Aquaporin 4 - immunology
Autoantibodies - blood
Epitope Mapping -
Epitopes - genetics
Female -
Flow Cytometry -
HEK293 Cells -
Humans -
Male -
Middle Aged -
Models, Molecular -
Mutagenesis -
Mutation - genetics
Neuromyelitis Optica - blood
Neuromyelitis Optica - immunology
Protein Binding - drug effects
Protein Binding - genetics
Protein Domains - genetics
Protein Isoforms - chemistry
Protein Isoforms - genetics
Sensitivity and Specificity -
Transfection -

Find related publications in this database (Keywords)
Neuromyelitis optica spectrum disorders
Aquaporin-4
Autoantibodies
Epitope specificity
Flow cytometry
© Meduni Graz Impressum