强直性脊柱炎早发髋关节强直与HLA-B27基因亚型的易感性研究
|
摘要
背景:前期临床研究中发现,人类白细胞抗原B27阳性与强直性脊柱炎早发髋关节强直具有强相关性。目的:分析强直性脊柱炎早发髋关节强直与人类白细胞抗原B27基因亚型的易感性,探讨人类白细胞抗原B27基因亚型在强直性脊柱炎早发髋关节强直发病中的作用。方法:收集具有完整病历资料的强直性脊柱炎早发髋关节强直患者300例,强直性脊柱炎非早发髋关节强直患者300例。研究经过广西壮族自治区人民医院伦理委员会审议通过,所有受试者及监护人均签署知情同意。采用病例-对照研究方案,其中强直性脊柱炎早发髋关节强直组,在其开始发病5年内,均有放射学检查(髋关节MRI、CT,骨盆X射线正侧位片)证实髋关节发生强直。收集2组患者一般情况和临床表现,采集患者2m L静脉血,通过PCR-SSP高分辨技术进行29种人类白细胞抗原B27基因亚型检测,计算人类白细胞抗原B27各基因亚型的构成比,分析相对危险度。结果与结论:①2组患者人类白细胞抗原B27检测的总阳性率为93.67%(562例):强直性脊柱炎早发髋关节强直组99.33%,强直性脊柱炎非早发髋关节强直组88.59%;②共找到29种人类白细胞抗原B27亚型中的6种,分别是B~*2702、B~*2703、B~*2704、B~*2705、B~*2706及B~*2713;2组均以B~*2704及B~*2705亚型为主,组间比较,B~*2704亚型在强直性脊柱炎非早发髋关节强直组所占比例最高(P <0.01),强直性脊柱炎早发髋关节强直组B~*2705亚型所占比例最高(P <0.01);③B~*2705亚型与强直性脊柱炎早发髋关节强直发病危险度相关(OR=1.896,95%可信区为1.221-3.218);④结果表明,强直性脊柱炎患者以B~*2704和B~*2705为主要亚型,其中B~*2705亚型是导致强直性脊柱炎患者早发髋关节强直的易感基因。B~*2705亚型可作为强直性脊柱炎早发髋关节强直早期诊断的重要参考指标。
BACKGROUND: Preliminary study has shown that positive for human leukocyte antigen-B27 is closely related to ankylosing spondylitis early-onset hip ankylosis.OBJECTIVE: To study the susceptibility of ankylosing spondylitis early-onset hip ankylosis and human leukocyte antigen-B27 gene subtype,and to explore the role of human leukocyte antigen-B27 gene subtype in the pathogenesis of ankylosing spondylitis early-onset hip ankylosis.METHODS: Three hundred cases of ankylosing spondylitis with early-onset hip ankylosis and 300 cases of ankylosing spondylitis without early-onset hip ankylosis were collected. The study was approved by the Ethics Committee of the People's Hospital of Guangxi Zhuang Autonomous Region, and all the participants and their guardians signed the informed consents. A case-control study was conducted, and the cases of ankylosing spondylitis with early-onset hip ankylosis were confirmed by radiological examinations(hip MRI, CT, pelvic X-ray film)within 5 years. The general condition and clinical manifestation of the subjects were collected. The 2 mL venous blood of each subject was collected for detecting the 29 human leukocyte antigen-B27 genotypes by PCR-SSP high resolution technique. The constituent ratio of human leukocyte antigen-B27 gene subtypes was calculated and relative risk was analyzed.RESULTS AND CONCLUSION:(1) The total positive rate of human leukocyte antigen-B27 detection in the two groups was 93.67%(562 cases), 99.33% in the ankylosing spondylitis with early-onset hip ankylosis group, and 88.59% in ankylosing spondylitis without early-onset hip ankylosis.(2) Six of the 29 types of human leukocyte antigen-B27 subtypes were found, which were B~*2702, B~*2703, B~*2704, B~*2705,B~*2706 and B~*2713. The two groups were mainly B~*2704 and B~*2705 subtypes. The proportion of B~*2704 subtypes in the ankylosing spondylitis without early-onset hip ankylosis group was highest(P < 0.01). The highest proportion in the ankylosing spondylitis with early-onset hip ankylosis group was B~*2705(P < 0.01).(3) B~*2705 subtype was associated with the risk of ankylosing spondylitis early-onset hip ankylosis(OR=1.896, 95%CI: 1.221-3.218).(4) In summary, the main subtypes of ankylosing spondylitis patients are B~*2704 and B~*2705,and the B~*2705 subtype is a susceptible gene that causes early-onset hip ankylosis in ankylosing spondylitis patients. The subtype of B~*2705 can be used as an important reference index for early diagnosis of ankylosing spondylitis early-onset hip ankylosis.
BACKGROUND: Preliminary study has shown that positive for human leukocyte antigen-B27 is closely related to ankylosing spondylitis early-onset hip ankylosis.OBJECTIVE: To study the susceptibility of ankylosing spondylitis early-onset hip ankylosis and human leukocyte antigen-B27 gene subtype,and to explore the role of human leukocyte antigen-B27 gene subtype in the pathogenesis of ankylosing spondylitis early-onset hip ankylosis.METHODS: Three hundred cases of ankylosing spondylitis with early-onset hip ankylosis and 300 cases of ankylosing spondylitis without early-onset hip ankylosis were collected. The study was approved by the Ethics Committee of the People's Hospital of Guangxi Zhuang Autonomous Region, and all the participants and their guardians signed the informed consents. A case-control study was conducted, and the cases of ankylosing spondylitis with early-onset hip ankylosis were confirmed by radiological examinations(hip MRI, CT, pelvic X-ray film)within 5 years. The general condition and clinical manifestation of the subjects were collected. The 2 mL venous blood of each subject was collected for detecting the 29 human leukocyte antigen-B27 genotypes by PCR-SSP high resolution technique. The constituent ratio of human leukocyte antigen-B27 gene subtypes was calculated and relative risk was analyzed.RESULTS AND CONCLUSION:(1) The total positive rate of human leukocyte antigen-B27 detection in the two groups was 93.67%(562 cases), 99.33% in the ankylosing spondylitis with early-onset hip ankylosis group, and 88.59% in ankylosing spondylitis without early-onset hip ankylosis.(2) Six of the 29 types of human leukocyte antigen-B27 subtypes were found, which were B~*2702, B~*2703, B~*2704, B~*2705,B~*2706 and B~*2713. The two groups were mainly B~*2704 and B~*2705 subtypes. The proportion of B~*2704 subtypes in the ankylosing spondylitis without early-onset hip ankylosis group was highest(P < 0.01). The highest proportion in the ankylosing spondylitis with early-onset hip ankylosis group was B~*2705(P < 0.01).(3) B~*2705 subtype was associated with the risk of ankylosing spondylitis early-onset hip ankylosis(OR=1.896, 95%CI: 1.221-3.218).(4) In summary, the main subtypes of ankylosing spondylitis patients are B~*2704 and B~*2705,and the B~*2705 subtype is a susceptible gene that causes early-onset hip ankylosis in ankylosing spondylitis patients. The subtype of B~*2705 can be used as an important reference index for early diagnosis of ankylosing spondylitis early-onset hip ankylosis.
引文
[1]Lee JH,Choi M,Rim THT, et al.Clinical Characteristics and Prognostic Factors in Ankylosing Spondylitis Associated Uveitis.Ocul Immunol Inflamm.2017:11:1-6.
[2]文钟,青玉凤,易婷,等.晚发型强直性脊柱炎的临床特点(附152例分析)[J].山东医药,2018,58(7):76-78.
[3]刘振峰,梁治权,洪汉刚,等.新疆地区维吾尔族与汉族强直性脊柱炎患者的差异性基因表达[J].中国组织工程研究, 2016,20(15):2233-2240.
[4]KaratasD, DoganI, Ekinci A, et al. Evaluation of auditory and cochlear functions in ankylosing spondylitis patients according to the site of involvement. Eur Arch Otorhinolaryngol. 2017;274(11):3875-3881.
[5]刘勇,孙俊英,王涛,等.全髋关节置换术治疗强直性脊柱炎累及髋关节的疗效观察[J].中国修复重建外科杂志, 2017, 31(1):25-30.
[6]吴文,锐罗斯,敏刘宁,等.全髋关节置换术对强直性脊柱炎髋关节病变患者工作能力及功能恢复的影响[J].南方医科大学学报,2018,7(20):879-883.
[7]熊春翔,卫小春,尹东,等.强直性脊柱炎早发髋关节强直相关影响因素的研究[J].中国矫形外科杂志, 2018, 26(9):798-801.
[8]Jeanty C,Sourisce A,Noteuil A,et al.HLA-B27 subtype oligomerization and intracellular accumulation patterns correlate with predisposition to spondyloarthritis.Arthritis Rheumatol.2014;66(8):2113-2123.
[9]张政,张毓洪,马玲玲,等.强直性脊柱炎遗传易感性基因的研究进展[J].中国老年保健医学杂志,2015,13(2):110-113.
[10]范春梅,黄荣富,陈根旺.闽南地区HLA-B27基因亚型与强直性脊柱炎相关性研究[J].中国微生态学杂志, 2016,28(3):256-258.
[11]Raychaudhuri SP, Deodhar A. The classification and diagnostic criteria of ankylosing spondylitis.J Autoimmun.2014;48-49:128-133.
[12]刘德琳,徐卫东,张宸,等.人工全髋关节置换术治疗强直性脊柱炎[J].协和医学杂志, 2017, 8(Z2):251-257.
[13]TanChing-Yuan,戴岷,谈裔,等.强直性脊柱炎合并髋关节累及患者骨质疏松症发病概况及相关因素分析[J].中国骨质疏松杂志, 2017, 23(7):856-859.
[14]Huang JC,Qian BP,Qiu Y,et al.Quality of life and correlation with clinical and radiographic variables in patients with ankylosing spondylitis:a retrospective case series study.BMC Musculoskelet Disord. 2017;18(1):352.
[15]Yang B,Xu Y,Liu X,et al.IL-23R and IL-17A polymorphisms correlate with susceptibility of ankylosing spondylitis in a Southwest Chinese population. Oncotarget. 2017;8(41):70310-70316.
[16]Slobodin G,Shpigelman A,Dawood H,et al. Craniocervical junction involvement in ankylosing spondylitis. Eur Spine J.2015;24(12):2986-2990.
[17]Weiss BG, Bachmann LM, Pfirrmann CW,et al.Whole Body Magnetic Resonance Imaging Features in Diffuse Idiopathic Skeletal Hyperostosis in Conjunction with Clinical Variables to Whole Body MRI and Clinical Variables in Ankylosing Spondylitis. J Rheumatol. 2016;43(2):335-342.
[18]Turan A, Tufan A, Mercan R, et al. Real-time sonoelastography of Achilles tendon in patients with ankylosing spondylitis. Skeletal Radiol. 2013;42(8):1113-1118.
[19]刘勇,霍少川,周驰,等.强直性脊柱炎患者全髋关节置换后异位骨化的危险因素[J].中国骨质疏松杂志, 2017, 21(11):1641-1646.
[20]颜则行,孙水,宋泽众,等.强直性脊柱炎髋关节非功能位骨性强直的人工全髋关节置换[J].中国矫形外科杂志, 2016, 24(7):623-626.
[21]Antoniou AN, Lenart I,Kriston-Vizi J,et al.Salmonellaexploits HLA-B27 and host unfolded protein responses to promote intracellular replication. Ann Rheum Dis.2019;78(1):74-82.
[22]Arévalo M,Gratacós MasmitjàJ,Moreno M,et al. Influence of HLA-B27on theAnkylosing Spondylitisphenotype:results from the REGISPONSER database. Arthritis Res Ther. 2018;20(1):221.
[23]罗秀霞,尹志华,张春容,等.荧光定量PCR染料法检测强直性脊柱炎患者HLA-B27基因及分型[J].国际检验医学杂志, 2018,39(13):1550-1552.
[24]宋红林,孟保福,李艳霞,等.强直性脊柱炎患者外周血淋巴细胞及血清PD-1、HLA-B27水平变化[J].山东医药, 2016, 56(16):55-57.
[25]段新旺,刘念,邹桂香,等. HLA-B27阳性与阴性中轴型脊柱关节炎临床特征分析[J].实用医学杂志, 2017, 33(12):1992-1995.
[26]Guiliano DB,North H,Panayoitou E,et al.Polymorphisms in the F Pocket ofHLA-B27 SubtypesStrongly Affect Assembly,Chaperone Interactions, and Heavy-Chain Misfolding.Arthritis Rheumatol. 2017;69(3):610-621.
[27]Mou Y, Wu Z, Gu J, Liao Z, et al.HLA-B27polymorphism in patients with juvenile and adult-onset ankylosing spondylitis in SouthernChina.Tissue Antigens.2010;75(1):56-60.
[28]Ziade NR.HLA B27antigen in Middle Eastern and Arab countries:systematic review of the strength of association with axial spondyloarthritis and methodological gaps.BMC Musculoskelet Disord.2017;18(1):280.
[29]吴震.强直性脊柱炎患者HLA-B27多态性及其与临床特点的相关性研究[D].广州:中山大学,2007.
[30]Chen B, Li J, He C,et al.Role of HLA-B27 in the pathogenesis of ankylosing spondylitis. Mol Med Rep. 2017;15(4):1943-1951.
[2]文钟,青玉凤,易婷,等.晚发型强直性脊柱炎的临床特点(附152例分析)[J].山东医药,2018,58(7):76-78.
[3]刘振峰,梁治权,洪汉刚,等.新疆地区维吾尔族与汉族强直性脊柱炎患者的差异性基因表达[J].中国组织工程研究, 2016,20(15):2233-2240.
[4]KaratasD, DoganI, Ekinci A, et al. Evaluation of auditory and cochlear functions in ankylosing spondylitis patients according to the site of involvement. Eur Arch Otorhinolaryngol. 2017;274(11):3875-3881.
[5]刘勇,孙俊英,王涛,等.全髋关节置换术治疗强直性脊柱炎累及髋关节的疗效观察[J].中国修复重建外科杂志, 2017, 31(1):25-30.
[6]吴文,锐罗斯,敏刘宁,等.全髋关节置换术对强直性脊柱炎髋关节病变患者工作能力及功能恢复的影响[J].南方医科大学学报,2018,7(20):879-883.
[7]熊春翔,卫小春,尹东,等.强直性脊柱炎早发髋关节强直相关影响因素的研究[J].中国矫形外科杂志, 2018, 26(9):798-801.
[8]Jeanty C,Sourisce A,Noteuil A,et al.HLA-B27 subtype oligomerization and intracellular accumulation patterns correlate with predisposition to spondyloarthritis.Arthritis Rheumatol.2014;66(8):2113-2123.
[9]张政,张毓洪,马玲玲,等.强直性脊柱炎遗传易感性基因的研究进展[J].中国老年保健医学杂志,2015,13(2):110-113.
[10]范春梅,黄荣富,陈根旺.闽南地区HLA-B27基因亚型与强直性脊柱炎相关性研究[J].中国微生态学杂志, 2016,28(3):256-258.
[11]Raychaudhuri SP, Deodhar A. The classification and diagnostic criteria of ankylosing spondylitis.J Autoimmun.2014;48-49:128-133.
[12]刘德琳,徐卫东,张宸,等.人工全髋关节置换术治疗强直性脊柱炎[J].协和医学杂志, 2017, 8(Z2):251-257.
[13]TanChing-Yuan,戴岷,谈裔,等.强直性脊柱炎合并髋关节累及患者骨质疏松症发病概况及相关因素分析[J].中国骨质疏松杂志, 2017, 23(7):856-859.
[14]Huang JC,Qian BP,Qiu Y,et al.Quality of life and correlation with clinical and radiographic variables in patients with ankylosing spondylitis:a retrospective case series study.BMC Musculoskelet Disord. 2017;18(1):352.
[15]Yang B,Xu Y,Liu X,et al.IL-23R and IL-17A polymorphisms correlate with susceptibility of ankylosing spondylitis in a Southwest Chinese population. Oncotarget. 2017;8(41):70310-70316.
[16]Slobodin G,Shpigelman A,Dawood H,et al. Craniocervical junction involvement in ankylosing spondylitis. Eur Spine J.2015;24(12):2986-2990.
[17]Weiss BG, Bachmann LM, Pfirrmann CW,et al.Whole Body Magnetic Resonance Imaging Features in Diffuse Idiopathic Skeletal Hyperostosis in Conjunction with Clinical Variables to Whole Body MRI and Clinical Variables in Ankylosing Spondylitis. J Rheumatol. 2016;43(2):335-342.
[18]Turan A, Tufan A, Mercan R, et al. Real-time sonoelastography of Achilles tendon in patients with ankylosing spondylitis. Skeletal Radiol. 2013;42(8):1113-1118.
[19]刘勇,霍少川,周驰,等.强直性脊柱炎患者全髋关节置换后异位骨化的危险因素[J].中国骨质疏松杂志, 2017, 21(11):1641-1646.
[20]颜则行,孙水,宋泽众,等.强直性脊柱炎髋关节非功能位骨性强直的人工全髋关节置换[J].中国矫形外科杂志, 2016, 24(7):623-626.
[21]Antoniou AN, Lenart I,Kriston-Vizi J,et al.Salmonellaexploits HLA-B27 and host unfolded protein responses to promote intracellular replication. Ann Rheum Dis.2019;78(1):74-82.
[22]Arévalo M,Gratacós MasmitjàJ,Moreno M,et al. Influence of HLA-B27on theAnkylosing Spondylitisphenotype:results from the REGISPONSER database. Arthritis Res Ther. 2018;20(1):221.
[23]罗秀霞,尹志华,张春容,等.荧光定量PCR染料法检测强直性脊柱炎患者HLA-B27基因及分型[J].国际检验医学杂志, 2018,39(13):1550-1552.
[24]宋红林,孟保福,李艳霞,等.强直性脊柱炎患者外周血淋巴细胞及血清PD-1、HLA-B27水平变化[J].山东医药, 2016, 56(16):55-57.
[25]段新旺,刘念,邹桂香,等. HLA-B27阳性与阴性中轴型脊柱关节炎临床特征分析[J].实用医学杂志, 2017, 33(12):1992-1995.
[26]Guiliano DB,North H,Panayoitou E,et al.Polymorphisms in the F Pocket ofHLA-B27 SubtypesStrongly Affect Assembly,Chaperone Interactions, and Heavy-Chain Misfolding.Arthritis Rheumatol. 2017;69(3):610-621.
[27]Mou Y, Wu Z, Gu J, Liao Z, et al.HLA-B27polymorphism in patients with juvenile and adult-onset ankylosing spondylitis in SouthernChina.Tissue Antigens.2010;75(1):56-60.
[28]Ziade NR.HLA B27antigen in Middle Eastern and Arab countries:systematic review of the strength of association with axial spondyloarthritis and methodological gaps.BMC Musculoskelet Disord.2017;18(1):280.
[29]吴震.强直性脊柱炎患者HLA-B27多态性及其与临床特点的相关性研究[D].广州:中山大学,2007.
[30]Chen B, Li J, He C,et al.Role of HLA-B27 in the pathogenesis of ankylosing spondylitis. Mol Med Rep. 2017;15(4):1943-1951.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |