Study On The Correlation Between Serum Concentration Of Kir4.1 Protein And The Clinical Features Of Neuromyelitis Optica Spectrum Disorders

Background and ObjectivesNeuromyelitis optica (NMO) is an autoimmune disease involving the central nervous system, mainly for its recur optic neuritis or (and) myelitis. Previous view that, NMO is one subtype of multiple sclerosis (MS); in 2004 the disease-specific immune biomarker aquaporin 4 (aquaporin-4, AQP4) antibody was found, since then, NMO was considered as an independent demyelinating disease of the central nervous system. However, as people getting deeper understanding of the disease, studies found that some pathogenesis of NMO was similar with non-specific inflammatory demyelinating disease. In 2007, Wingerchuk summarized and presented the concept-neuromyelitis optica spectrum disorders(NMOSD).2015 Wingerchuk et al proposed NMOSD disease diagnosis consensus further. NMOSD has a high recurrence rate, what’s worse, NMOSD patients get higher morbidity and mortality than MS patients. Inwardly rectifying potassium ion(Kir) refers to the degree of permeability K+influx is greater than K+efflux and transparent degree of a class of potassium channel protein, Kir4.1 is a subtype of Kir, mainly express on oligodendrocytes and astrocytes endfeet. Studies suggest that, Kir4.1 aquaporin 4 may work together to maintain the balance of potassium ions and water, which to maintain the stability of intracellular osmotic pressure. Moreover, people thought that Kir4.1 may be involved in the pathogenesis of central nervous system demyelinating disease.In this study, we detected the serum concentration of Kir4.1 in patients with NMOSD, and analyzed the relationship between it and clinical features of the disease, then explore the role of serum Kir4.1 played in the pathogenic of NMOSD disease.MethodsCollect the NMOSD patients admitted to the department of neurology in the First Affiliated Hospital of Zhengzhou University from October 2013 to December 2015 [including NMO 18 cases, bilateral optic neuritis (BON) 2 cases long segment transverse myelitis (LETM) 8 cases,2 cases of brain stem encephalitis]; collected the serum in the acute phase and after clinical treatment, measured the concentration of Kir4.1 in the serum. Other non-inflammatory neurological disease group (ONND) 20 patients [including seven cases of transient ischemic attack (TIA),4 patients with benign paroxysmal positional vertigo (BPPV),5 patients with idiopathic epilepsy, four cases of multiple system atrophy]. Select the same period healthy volunteers (Healthy Control, HC) 18 cases for the control group. By enzyme-linked immunosorbent assay (ELISA) determining a level of case group and the control group serum Kir4.1 law. Using software SPSS17.0 to handle all the data, using the mean ± standard deviation (χ ± s) expressed in the form of quantitative data. Using two independent samples t test was used for quantitative data were compared using ANOVA group more quantitative data, and then using pairwise comparison (LSD-t-test), when P<0.05, it means the difference statistically significant.Results1.NMOSD group compared with serum levels in patients with non-NMOSD group Kir4.1NMOSDs serum levels of acute phase Kir4.1 was 89.09 ± 33.71pg/ml, ease serum levels of Kir4.1 was 130.27 ± 43.72pg/ml, ONND Kir4.1 serum levels of 201.20 ± 41.59pg/ml; healthy control group Kir4.1 serum level of 230.49 ± 76.36pg /ml; NMOSD serum levels of acute phase compared with Kir4.1 NMOSD remission (P<0.01), respectively, ONND group (P<0.01) and the HC group (P<0.01) lower, the differences were statistically significant.2.Relationship between serum levels of Kir4.1 and AQP4 serum antibodies NMOSD acute groupNMOSD group of patients with acute phase serum AQP4 antibody positive serum levels of Kir4.181.23±32.18pg/ml, serum AQP4 antibody-negative group was 110.70±29.56pg/ml; low serum AQP4 antibody positive group, serum levels of Kir4.1 in AQP4-negative group, the difference was statistically significant (p= 0.03).3.Relations between NMOSD acute phase serum levels and EDSS score of Kir4.1NMOSD group of patients with acute, EDSS score<5 Kir4.1 grouping serum levels of 106.30+31.59pg/ml, EDSS score≥5 grouped 69.45±24.58pg/ml; EDSS score<5 packets of high serum levels of Kir4.1 in EDSS score>5 group, the difference was statistically significant (p= 0.002).4.Relations between NMOSD acute phase serum levels of Kir4.1 and the spinal cord lesion segmentsNMOSD group of patients with acute lesions involving vertebral segments<3 serum levels of Kir4.1 group was 118.10±17.00pg/ml, spinal cord lesion segment≥3 vertebral group was 84.55±33.69pg/ml; NMOSD acute phase patients, spinal cord lesions segment<3 vertebral serum levels were higher than Kir4.1 lesion spinal segment≥3 vertebral group, the difference was statistically significant (p= 0.04).Conclusion1. Kir4.1 may be involved in the pathogenesis of NMOSD, which reduce their expression or disturbs the homeostasis in the glial cells, leading to diseases.2.AQP4 antibodies may by acting on AQP4 and Kir4.1 common sites, reduce the expression of Kir4.1 participate NMOSD pathogenic process.3. Serum levels may Kir4.1 with disease severity, serum Kir4. the lower level 1, the more severe the disease.