视神经脊髓炎谱系疾病患者的HLA-DP基因表达

Expression of HLA-DP in patients with neuromyelitis optica spectrum disorders

目的探讨HLA-DP基因表达对视神经脊髓炎谱系疾病(NMOSD)的发病和疾病状态的影响.方法前瞻性收集2016年7月至2017年12月在中山大学附属第三医院神经内科就诊的NMOSD患者86例(急性期52例,缓解期34例)、多发性硬化(MS)患者52例(急性期20例,缓解期32例)及健康对照29名,采用流式细胞技术及RT-PCR法,对其外周血抗原呈递细胞(包括B细胞及单核细胞)表面HLA-DP分子表达及外周血单个核细胞(PBMC)HLA-DPB1 mRNA转录水平进行研究.结果HLA-DPB1*0501/HLA-DPB1*0501、HLA-DPB1*0501/X、X/X三种基因型分布及HLA-DPB1*0501等位基因型频数分布在NMOSD、MS及健康对照组间比较差异无统计学意义(P=0.96,P=0.71).NMOSD患者,尤其是缓解期NMOSD患者外周血B细胞表面HLA-DP分子表达水平显著高于健康对照组(分别为212±328和374±394比55±57,P=0.049,P=0.002),急性期NMOSD患者外周血单核细胞表面HLA-DP分子表达水平显著高于健康对照组(158±175比65±90,P=0.025);NMOSD急性期和缓解期PMBC HLA-DPB1 mRNA的转录水平均显著高于健康对照组(3.0±1.4和2.9±1.3 vs 1.5±1.4,P分别为0.000和0.003);MS患者急性期及缓解期外周血B细胞及单核细胞表面HLA-DP分子表达水平及PBMC HLA-DPB1 mRNA的转录水平均与健康对照组比较差异无统计学意义.HLA-DPB1*0501/HLA-DPB1*0501、HLA-DPB1*0501/X、X/X三种基因型的患者外周血B细胞表面HLA-DP分子表达水平比较差异有统计学意义(P=0.017).结论抗原呈递细胞HLA-DP基因转录及分子表达水平可能影响NMOSD的易感性及疾病状态,而HLA-DPB1*0501等位基因型可能影响抗原呈递细胞HLA-DP基因转录及分子表达水平.

Objective To investigate the effect of HLA-DP gene expression on the susceptibility and disease status of neuromyelitis optica spectrum disorders(NMOSD).Methods A total of 86 NMOSD patients(52 in acute phase and 34 in remission phase),52 multiple sclerosis(MS)patients(20 in acute phase and 32 in remission phase)diagnosed in Department of Neurology,the Third Affiliated Hospital of Sun Yat-sen University and 29 healthy controls were enrolled prospectively.Genotyping of HLA-DP was performed.The expression levels of HLA-DP molecules in peripheral blood B cells and monocytes were measured by flow cytometry.The transcription levels of HLA-DPB1 mRNA in peripheral blood mononuclear cells(PBMC)were measured by real time-PCR.The results were compared among different groups Results There was no statistically significant difference of the distributions of HLA-DPB1*0501/HLA-DPB1*0501,HLA-DPB1*0501/X and X/X genotypes and the frequencies of allele of HLA-DPB1*0501 among NMOSD,MS patients and healthy controls(P=0.96 and 0.71,respectively).The expression levels of HLA-DP on the surface of B cells in NMOSD patients,especially in remission phase patients,were significantly higher than those in healthy controls(212±328 and 374±394 vs 55±57,P=0.049 and 0.002,respectively).The expression levels of HLA-DP on the surface of monocytes in NMOSD patients in acute phase were significantly higher than those in healthy controls(158±175 vs 65±90,P=0.025).The transcription levels of PMBC HLA-DPB1 mRNA in acute phase and remission phase of NMOSD patients were significantly higher than those in healthy controls(3.0±1.4 and 2.9±1.3 vs 1.5±1.4,P=0.000 and 0.003,respectively).The expression levels of HLA-DP molecules on the surface of peripheral blood B cells and monocytes and the transcription levels of PMBC HLA-DPB1 mRNA in MS patients at the acute and remission stages were not significantly different from those in healthy controls.The expression levels of HLA-DP molecules on the surface of B cells in patients with HLA-DPB1*0501/HLA-DPB1*0501,HLA-DPB1*0501/X and X/X genotypes were statistically different(P=0.017).Conclusion HLA-DP gene transcription and molecular expression levels in antigen presenting cells may affect the susceptibility and disease status of NMOSD patients,while HLA-DPB1*0501 allele may affect the transcription and molecular expression levels of HLA-DP gene in antigen presenting cells.