B-101 Aquaporin 4 and Neuromyelitis Optica Spectrum Disorders
Authors: Gonzalez Cejudo T , de Haro Romero T , Papay Ramirez L , Lopez Velez M , de Haro Muñoz T 
Published: September 2023

Background

Neuromyelitis óptica (NMO) is a rare demyelinating inflammatory disease of the central nervous system, characterized by acute optic neuritis (ON) and transverse myelitis (TM). Previously, it was considered as a variant of multiple sclerosis (MS), however, there are now several clinical, laboratory, neuroimaging and pathological anatomical features that distinguish it from MS as the presence of a specific autoantibody in blood called IgG-NMO or anti-AQP4 that binds to water channels named aquaporin-4 (AQP4) expressed on astrocytes and plays a key role in the pathogenesis of this disease. Some patients remain seronegative for AQP4-IgG despite a definite diagnosis of NMO and the use of the finest methods for antibody detection. In anti-AQP4 seronegative forms, antibodies against myelin oligodendrocyte glycoprotein (MOG) may be identified. We have carried out a review of those patients with anti-AQP4-IgG detected in the autoimmunity laboratory during the last 3 years.

Methods

Each year we receive an average of 260 samples from patients with suspected demyelinating pathology with or without visual impairment. For the detection of antibodies against AQP-4 specifically HEK293 cells transfected were used as the standard substrate. Anti-MOG antibody can be detected in the same test. Measurement range: The dilution starting point for this measurement system is 1:10 (serum/plasma) and 1:1 (CSF, undiluted).

Results

A total of 5 patients were positive for anti AQP-4 antibody in serum samples, all women aged between 23 and 78 years. All patients except the youngest, who presented to the neurology department for loss of visual acuity, had other autoimmune diseases: systemic lupus erythematosus (SLE) in conjunction with rheumatoid arthritis, SLE in conjunction with Graves’ disease and hypothyroidism, the two oldest (59 and 78 years), respectively. The oldest patient was admitted to the internal medicine department for persistent nausea, vomiting and hiccups and was diagnosed as NMO spectrum disorder. In all cases, the oligoclonal immunoglobulin G bands study in CSF was negative. None of the CSF samples tested were positive for anti AQP-4 antibody. All patients were treated with methylprednisolone, but treatment with azathioprine or rituximab was necessary in 3 patients.

Conclusion

Titers of antibodies against AQP-4 are significantly higher in serum than in CSF, with serum being the most sensitive simple. NMO is more prevalent in women than men, with a female predominance usually higher than observed in MS. The median age of onset is also higher than MS, with a median of 35–45 years. Since the discovery of AQ-4 antibodies, there has been an increase in the number of clinical and radiological manifestations of NMO beyond involvement of the optic nerve and the spinal cord, including manifestations in the brain. It is important to recognise them in order to make an early diagnosis, to avoid unnecessary complementary tests and to establish the most suitable treatment. Persistent and intractable hiccups and nausea may occur in 17%–43% as in our oldest patient’s case. Associations with organ-specific autoimmune diseases such as autoimmune thyroiditis, and non-organ-specific diseases such as SLE and Sjögren’s syndrome have been described.