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Abstract Number: 2819

Clinical Utility of Anti-Aquaporin 4 Antibody Measurement in Patients with Neuropsychiatric Systemic Lupus Erythematosus with Neuromyelitis Optica Spectrum Disorder Manifestations

Simone Mader1, Yoshiyuki Arinuma1, Venkatesh Jeganathan1, Yuichiro Fujieda2, Irena Dujmovi3, Jelen Drulovic3, Yuko Sakuma4, Shinsuke Yasuda5, Joel Stern6, Cynthia Aranow6, Meggan Mackay7, Tatsuya Atsumi5, Shunsei Hirohata8 and Betty Diamond9, 1Center of Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Manhasset, NY, 2Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan, 3Clinical Centre of Serbia University School of Medicine, Belgrade, Serbia, 4Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, Kanagawa, Japan, 5Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan, 6The Feinstein Institute for Medical Research, Manhasset, NY, 7Autoimmune & Musculoskeletal Disorders, The Feinstein Institute for Medical Research, Manhasset, NY, 8Rheumatology and Infectious Diseases, Kitasato University School of Medicine, Kanagawa, Japan, 9Autoimmune & Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Manhasset, NY

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: autoantibodies, central nervous system involvement, neuropsychiatric disorders and systemic lupus erythematosus (SLE)

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Session Information

Date: Tuesday, November 15, 2016

Session Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment - Poster III: Biomarkers and Nephritis

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:  Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by the presence of autoantibodies. Among the complications of SLE, neuropsychiatric manifestations (NPSLE) can be very severe. They should be managed according to the disease pathogenesis. Previously we have shown that autoantibody against the amino acid sequence, DWEYS, a consensus sequence in the extracellular domain of the GluN2A/GluN2B subunits of the N-methyl-D-aspartate receptor (NMDAR) can induce apoptosis of hippocampal neurons through excitotoxicity and cause cognitive disorders in mice. DWEYS peptide reactive antibody displays reactivity to dsDNA with high affinity and is found in patients with NPSLE as well as SLE. Neuromyelitis optica spectrum disorders (NMOSD) are characterized by central nervous system damage, most commonly optic neuritis and acute myelitis, which can also be observed in NPSLE, and the presence of anti-aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) in serum. However, association of NMOSD and AQP4-IgG in patients with NPSLE, especially complicated with manifestations of demyelination, has not been studied. The purpose of this study is to determine the utility of AQP4-IgG in NPSLE with NMOSD based on a large multicenter cohort study.

Methods:  Sera of NPSLE patients (n=108), SLE (n=38) and healthy individuals (n=83) were collected from institutes in Europe, Japan and United States. As a disease control group, sera from 35 patients with NMOSD without any other autoimmune diseases were also used for this retrospective analysis. AQP4-IgG in serum were measured by a live cell-based assay using human embryonic kidney cells expressing AQP4. In addition, we measured serum anti-DWEYS antibodies as well as anti-dsDNA antibodies using an ELISA.

Results:  Of 108 patients diagnosed as NPSLE, 9 patients had demyelination classified according to ACR nomenclature for NPSLE in 1999, which could be also diagnosed as manifestation of NMOSD. Of the 9 patients with demyelination syndromes, 4 patients exhibited positivity for AQP4-IgG (44%) and 2 were seropositive for both DWEYS peptide and for AQP4-IgG. In all NPSLE patients without demyelination syndromes as well as in all SLE patients without neuropsychiatric syndromes and healthy controls, AQP4-IgG serostatus was negative. In 25/35 (71%) of NMOSD patients without any other autoimmune disease, the AQP4 IgG serostatus was positive. Anti-DWEYS antibody was detected in 1 (2%) of the 35 patients with NMOSD alone. DWEYS peptide reactivity didn’t differ between patients with NMOSD alone and healthy controls.

Conclusion:  In NPSLE patients with demyelination such as myelitis which is commonly seen in NMOSD, measurement of AQP4-IgG with our live cell based assay has a great advantage for diagnosis. Our results suggest AQP4-IgG testing patients with NPSLE and demyelinating syndrome. It is also possible that there could be other autoantibody specificities causing manifestation of NMOSD in patients with NPSLE negative for AQP4-IgG.


Disclosure: S. Mader, None; Y. Arinuma, None; V. Jeganathan, None; Y. Fujieda, None; I. Dujmovi, None; J. Drulovic, None; Y. Sakuma, None; S. Yasuda, None; J. Stern, None; C. Aranow, None; M. Mackay, None; T. Atsumi, None; S. Hirohata, None; B. Diamond, None.

To cite this abstract in AMA style:

Mader S, Arinuma Y, Jeganathan V, Fujieda Y, Dujmovi I, Drulovic J, Sakuma Y, Yasuda S, Stern J, Aranow C, Mackay M, Atsumi T, Hirohata S, Diamond B. Clinical Utility of Anti-Aquaporin 4 Antibody Measurement in Patients with Neuropsychiatric Systemic Lupus Erythematosus with Neuromyelitis Optica Spectrum Disorder Manifestations [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/clinical-utility-of-anti-aquaporin-4-antibody-measurement-in-patients-with-neuropsychiatric-systemic-lupus-erythematosus-with-neuromyelitis-optica-spectrum-disorder-manifestations/. Accessed January 19, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-utility-of-anti-aquaporin-4-antibody-measurement-in-patients-with-neuropsychiatric-systemic-lupus-erythematosus-with-neuromyelitis-optica-spectrum-disorder-manifestations/

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