Study Of FcRL3 In Multiple Sclerosis And Neuromyelitis Optica

Objective: Multiple sclerosis and neuromyelitis optica are complex autoimmune diseases whose pathogenesis involved with genes and environmental factors. Looking for genes associated with its onset and exploring its pathogenesis is of great importance for the understanding of the etiology and pathogenesis. In our preliminary results, the polymorphism rs7528684 locus in Fc RL3 gene promoter region was associated with MS and NMO in Chinese Han population and the loci may affect the gene transcription that patients carrying C allele had higher Fc RL3 expression. In addition, Fc RL3 transcription decreased in the acute phase of the patients, indicating that Fc RL3 might be a protective factor in patients. Fc RL3 had intracellular tyrosine receptor activation motif and tyrosine receptor inhibition motif, which implied its potential immune regulation function. However, the immune cell type and the mechanism how Fc RL3 function remained unknown. Our work was to further study the relevance between this functional site and the serum cytokinesis in MS and NMO, aiming to gain a preliminary understanding of the immune regulator function of Fc RL3.Methods: Induce the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis(EAE), and detect Fc RL3 m RNA level of spleen cells by fluorescent quantitation polymerase chain reaction(QPCR)in EAE. Collecting blood samples of 31 acute MS patients, 64 acute NMO patients and 71 normal controls. Cytometric Bead Array was applied to detect serum IL-2, IL-4, IL-6, IL-10, IL-17 a, TNF-a, IFN-?concentration. Flow cytometry were utilized to analyze the proportion of Th17 cells and Treg cells in peripheral blood.Results:1. The expression level of Fc RL5 gene was significantly lower in EAE compared to normal mouse, which reached statistic difference.2. The serum level of IL6 and IL17 a was higher in MS patients than that in healthy controls, while IL2 level was lower. In NMO patents, the level of IL17 a in serum was higher than that in healthy group, while IL2 was lower. The differences were of statistical significance. IL6 was higher in MS group when comparing MS and NMO group.3, According to the different allele on rs7528684 lied in the promoter region of Fc RL3 gene, MS NMO patients and normal controls were divided into three groups with variant genotypes of CC/CT/TT,respectively. In MS group, patients with CC or CT genotype had higher levels of IL10 in serum compared to those with TT genotype(CC vs TT p=0.0194,CT vs TT p=0.0282).4. Compared to the control group, the proportion of Th17 cells in peripheral blood of MS and NMO patients elevated, while the proportion of Treg cells decreased. The axis of Th17 / Treg cells skewed to Th17 cells. This phenomenon was more evident in MS patients.5. According to genotype of rs7528684 in Fc RL3 gene, MS and NMO patients were subdivided into three groups and Th17 / Treg cells were evaluated. due to the small samples of patients with the CC genotype,only comparison of CT and TT genotypes was conducted. No statistically significant differences were found.Conclusions:1. Fc RL5 expression was lower in EAE, suggesting that it might be a protective factor. The change of Fc RL5 in EAE was the same as the trend of its homologous protein Fc RL3 in MS patients, indicating that we could do further function study of Fc RL5 in EAE to reveal the function of Fc RL3 in patients.2. The polymorphism of rs7528684 in the gene promotor region of signal costimulatory molecular Fc RL3 on multiple immunocytes was associated with the level of serum IL10 in MS patients.