Email Alert | RSS

北京大学学报（医学版） ›› 2023, Vol. 55 ›› Issue (6): 1088-1096. doi: 10.19723/j.issn.1671-167X.2023.06.021

• 论著 • 上一篇    下一篇

CENP-B抗体阳性的原发性干燥综合征患者的临床和免疫学特征

孟彦宏1,陈怡帆2,周培茹3,*()   

  1. 1. 北京大学口腔医学院·口腔医院检验科，国家口腔医学中心，国家口腔疾病临床医学研究中心，口腔生物材料和数字诊疗装备国家工程研究中心，北京 100081
    2. 北京大学口腔医学院·口腔医院信息中心，国家口腔医学中心，国家口腔疾病临床医学研究中心，口腔生物材料和数字诊疗装备国家工程研究中心，北京 100081
    3. 北京大学口腔医学院·口腔医院口腔黏膜科，国家口腔医学中心，国家口腔疾病临床医学研究中心，口腔生物材料和数字诊疗装备国家工程研究中心，北京 100081
  • 收稿日期:2022-10-09 出版日期:2023-12-18 发布日期:2023-12-11
  • 通讯作者: 周培茹 E-mail:zhoupeiru1989@163.com
  • 基金资助:
    北京大学口腔医院新技术新疗法项目(PKUSSNCT-21B13)

Clinical and immunological features of primary Sjögren's syndrome patients with positive anti-centromere protein B antibody

Yan-hong MENG1,Yi-fan CHEN2,Pei-ru ZHOU3,*()   

  1. 1. Department of Clinical Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
    2. Department of Information Center, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
    3. Department of Oral Medicine, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
  • Received:2022-10-09 Online:2023-12-18 Published:2023-12-11
  • Contact: Pei-ru ZHOU E-mail:zhoupeiru1989@163.com
  • Supported by:
    the Program for New Clinical Techniques and Therapies of Peking University School and Hospital of Stomatology(PKUSSNCT-21B13)

RICH HTML

 1   

PDF (PC)

125

摘要：

目的: 探讨着丝点蛋白B(centromere protein B, CENP-B)抗体阳性的原发性干燥综合征(primary Sjögren’s syndrome, pSS)患者的临床和免疫学特征。方法: 采用横断面研究的研究设计, 回顾性纳入2016年1月至2022年8月就诊于北京大学口腔医院并确诊为pSS的患者, 收集分析患者的一般及临床特征、唾液腺造影、唇腺活检病理、血清免疫学及生化检查等资料。将pSS患者分为CENP-B抗体阳性组和阴性组, 用SPSS 23.0软件对数据进行描述性分析、单因素及相关性分析, 并将CENP-B抗体阳性组分为CENP-B抗体单阳性组及合并其他抗体阳性组进行亚组分析。结果: 共纳入288例pSS患者, 其中CENP-B抗体阳性组75例(26.0%), 阴性组213例(74.0%)。CENP-B抗体阳性组的发病年龄较大, 罹患自身免疫性肝病的比例较高, 唾液腺肿大的比例较低, SSA/Ro60、Ro52、SSB抗体的阳性率均较低, 免疫球蛋白G、类风湿因子的水平较低, 免疫球蛋白M的水平较高, 总蛋白水平较低, 而白蛋白/球蛋白比值、谷丙转氨酶、谷草转氨酶、碱性磷酸酶、γ-谷氨酰转移酶、乳酸脱氢酶的水平较高。亚组分析显示, CENP-B抗体单阳性组的总蛋白、免疫球蛋白A水平低于合并其他抗体阳性组。结论: CENP-B抗体阳性的pSS患者具有独特的临床和免疫学特征, 表现为疾病活动性较低, 较少发生唾液腺肿大, 但易罹患自身免疫性肝病, 肝功能生化指标水平偏高, 提示CENP-B抗体可能是pSS亚型分类的特异性标志物。

关键词: 着丝点蛋白质B抗体, 原发性干燥综合征, 自身抗体, 免疫学特征

Abstract:

Objective: To investigate the clinical and immunological features of primary Sjögren's syndrome (pSS) patients with positive anti-centromere protein B (CENP-B) antibody. Methods: In this cross-sectional study, the general clinical data, radiographic examination and labial salivary gland biopsy data, and serum immunological and biochemical data of patients diagnosed with pSS from January 2016 to August 2022 were evaluated. The included patients were divided into the anti-CENP-B antibody positive and negative groups. Intergroup differences were analyzed with SPSS 23.0 software. Subgroup analysis was further performed by dividing the anti-CENP-B antibody positive group into the single anti-CENP-B antibody positive and with other auto-antibodies positive groups to determine the characters related to anti-CENP-B antibody. Results: In this study, 288 patients with pSS were evaluated, including 75 patients with anti-CENP-B antibody positive and 213 with anti-CENP-B antibody negative. Univariate analysis showed that compared with the anti-CENP-B antibody negative group, the patients of the anti-CENP-B antibody positive group were older, had lower proportion of the patients with salivary gland enlargement and higher proportion of autoimmune liver disease. As for immunological indicators, the positive proportions of anti-SSA/Ro60, anti-Ro52, and anti-SSB antibodies were significantly lower. Moreover, the immunoglobulin (Ig) G and rheumatoid factor levels were significantly lower, while the IgM level was significantly higher in the patients of the anti-CENP-B antibody positive group. As for serum biochemical indicators, for the patients of the anti-CENP-B antibody positive group, the level of total protein (TP) was lower, the albumin/globulin ratio was higher, and the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH) were higher. Subgroup analysis showed that the levels of TP and IgA in the patients of the single anti-CENP-B antibody positive group were significantly lower than those of the patients with other autoantibodies positive group. Conclusion: The pSS patients with anti-CENP-B antibody positive have unique clinical and immunological features of lower disease activity, less likely to involve salivary gland, higher risk for autoimmune liver disease, and higher levels of liver function indicators. Anti-CENP-B antibody may be a marker for a distinct subset of polyautoimmunity in Sjögren's syndrome.

Key words: Centromere protein B antibody, Primary Sjögren's syndrome, Autoantibodies, Immuno-logical features

中图分类号: 

  • R593.2

图1

pSS患者筛选及分组流程图"

表1

CENP-B抗体阳性组和阴性组pSS患者一般及临床特征资料的比较"

Characteristics Anti-CENP-B antibody (-)(n=213) Anti-CENP-B antibody (+)(n=75) P
Gender, n (%) 0.927
  Male 11 (5.2) 3 (4.0)
  Female 202 (94.8) 72 (96.0)
Age at diagnosis/years, M (P25, P75) 53.0 (38.5, 62.0) 63.0 (54.0, 71.0) < 0.001
Dry mouth symptom duration/months, M (P25, P75) 24 (6, 72) 36 (12, 60) 0.335
UWS ≤0.1 mL/min*, n/total (%) 112/116 (96.6) 42/44 (95.5)
Salivary glands enlargement, n (%) 98 (46.0) 22 (29.3) 0.012
Abnormal conventional X-ray sialography*, n/total (%) 138/151 (91.4) 37/43 (86.0)
LSG biopsy*, n/total (%)
  FLS and FS = 1 foci/4 mm2 10/39 (25.6) 8/33 (24.2)
  FLS and FS = 2 foci/4 mm2 8/39 (20.5) 5/33 (15.2)
  FLS and FS = 3 foci/4 mm2 3/39 (7.7) 4/33 (12.1)
  FLS and FS ≥ 4 foci/4 mm2 18/39 (46.2) 16/33 (48.5)
Dry eyes symptom, n (%) 127 (59.6) 52 (69.3) 0.136
Abnormal Schirmer’s test* or OSS*, n (%) 69 (32.4) 26 (34.7)
Joint involvement, n (%) 41 (19.2) 21 (28.0) 0.113
Hypertension, n (%) 39 (18.3) 15 (20.0) 0.747
Autoimmune liver disease, n (%) 1 (0.5) 4 (5.3) 0.024

表2

自身免疫抗体和其他免疫指标的组间比较"

Characteristics Anti-CENP-B antibody (-)(n=213) Anti-CENP-B antibody (+)(n=75) P
Anti-mitochondrial antibody M2, n (%) 12 (5.6) 7 (9.3) 0.401
Anti-ribosomal P-proteins antibody, n (%) 9 (4.2) 3 (4.0) > 0.999
Anti-histones antibody, n (%) 6 (2.8) 1 (1.3) 0.778
Anti-nucleosome antibody, n (%) 3 (1.4) 6 (8.0) 0.015
Anti-dsDNA antibody, n (%) 9 (4.2) 3 (4.0) > 0.999
Anti-PCNA antibody, n (%) 1 (0.5) 0 (0) > 0.999
Anti-Jo-1 antibody, n (%) 5 (2.3) 1 (1.3) 0.953
Anti-PM-Scl antibody, n (%) 5 (2.3) 1 (1.3) 0.953
Anti-Scl-70 antibody, n (%) 3 (1.4) 2 (2.7) 0.839
Anti-SSB antibody, n (%) 108 (50.7) 10 (13.3) < 0.001
Anti-Ro52 antibody, n (%) 178 (83.6) 39 (52.0) < 0.001
Anti-SSA/Ro60 antibody, n (%) 190 (89.2) 36 (48.0) < 0.001
Anti-Sm antibody, n (%) 4 (1.9) 4 (5.3) 0.247
Anti-nRNP/Sm antibody, n (%) 17 (8.0) 3 (4.0) 0.243
IgG/(g/L), M (P25, P75) 19.55 (16.24, 24.73) 17.90 (13.51, 19.12) < 0.001
IgA/(g/L), M (P25, P75) 2.91 (2.33, 3.65) 2.91 (2.03, 3.50) 0.154
IgM/(g/L), M (P25, P75) 1.34 (0.92, 1.65) 1.34 (1.07, 2.42) 0.017
C3/(g/L), ${\bar x}$±s 1.313±0.238 1.310±0.227 0.074
RF/(g/L), M (P25, P75) 30.47 (19.30, 105.89) 18.20 (5.55, 30.42) < 0.001

表3

免疫球蛋白与CENP-B抗体的相关性分析"

Items P value OR (95% CI)
IgG* < 0.001 0.897 (0.850-0.947)
IgM* 0.007 1.321 (1.079-1.618)

表4

组间血清生化指标的比较"

Characteristics Anti-CENP-B antibody (-) (n=213) Anti-CENP-B antibody (+) (n=75) P
TP/(g/L), M (P25, P75) 80.0 (75.7, 84.0) 75.0 (72.0, 81.0) < 0.001
Alb/(g/L), M (P25, P75) 43.7 (41.7, 46.0) 44.0 (42.3, 46.0) 0.372
A/G, ${\bar x}$±s 1.240±0.270 1.410±0.266 < 0.001
ALT/(U/L), M (P25, P75) 16.0 (12.0, 21.8) 19.5 (14.0, 28.0) 0.014
AST/(U/L), M (P25, P75) 20.0 (17.0, 26.0) 24.0 (19.0, 31.0) 0.001
AST/ALT, M (P25, P75) 1.29 (1.00, 1.61) 1.31 (1.09, 1.45) 0.089
TBIL/(μmol/L), M (P25, P75) 12.08 (9.80, 15.87) 12.54 (10.10, 15.01) 0.777
DBIL/(μmol/L) M (P25, P75) 2.91 (2.26, 3.80) 3.20 (2.47, 4.05) 0.188
ALP/(U/L), M (P25, P75) 73.0 (67.0, 80.0) 73.0 (70.0, 99.0) 0.034
GGT/(U/L), M (P25, P75) 18.0 (14.9, 20.0) 18.0 (14.0, 35.0) 0.046
CK/(U/L), M (P25, P75) 64.0 (55.0, 73.5) 64.0 (52.0, 81.0) 0.652
LDH/(U/L), M (P25, P75) 171.0 (152.5, 175.0) 171.0 (171.0, 194.0) < 0.001

表5

根据CENP-B抗体及其他自身抗体阳性情况的亚组分析"

Characteristics Anti-CENP-B antibody (+) alone(n=24) Anti-CENP-B and other autoantibodies (+)(n=51) P
IgA/(g/L), M (P25, P75) 2.11 (1.78, 2.91) 2.91 (2.24, 3.74) 0.027
TP/(g/L), M (P25, P75) 72.6 (69.2, 76.5) 76.6 (73.0, 82.0) 0.032
1 Mavragani CP , Moutsopoulos HM . Sjögren syndrome[J]. CMAJ, 2014, 186 (15): E579- E586.
doi: 10.1503/cmaj.122037
2 Stefanski AL , Tomiak C , Pleyer U , et al. The diagnosis and treatment of Sjögren's syndrome[J]. Dtsch Arztebl Int, 2017, 114 (20): 354- 361.
3 Shiboski CH , Shiboski SC , Seror R , et al. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for primary Sjögren's syndrome: A consensus and data-driven methodology involving three international patient cohorts[J]. Arthritis Rheumatol, 2017, 69 (1): 35- 45.
doi: 10.1002/art.39859
4 Yoda K , Kitagawa K , Masumoto H , et al. A human centromere protein, CENP-B, has a DNA binding domain containing four potential alpha helices at the NH2 terminus, which is separable from dimerizing activity[J]. J Cell Biol, 1992, 119 (6): 1413- 1427.
doi: 10.1083/jcb.119.6.1413
5 Tanaka Y , Nureki O , Kurumizaka H , et al. Crystal structure of the CENP-B protein-DNA complex: The DNA-binding domains of CENP-B induce kinks in the CENP-B box DNA[J]. EMBO J, 2001, 20 (23): 6612- 6618.
doi: 10.1093/emboj/20.23.6612
6 Baer AN , Medrano L , McAdams-DeMarco M , et al. Association of anticentromere antibodies with more severe exocrine glandular dysfunction in Sjögren's syndrome: Analysis of the Sjögren's International Collaborative clinical alliance cohort[J]. Arthritis Care Res (Hoboken), 2016, 68 (10): 1554- 1559.
doi: 10.1002/acr.22859
7 Tsukamoto M , Suzuki K , Takeuchi T . Clinical and immunological features of anti-centromere antibody-positive primary Sjögren's syndrome[J]. Rheumatol Ther, 2018, 5 (2): 499- 505.
doi: 10.1007/s40744-018-0126-2
8 Nakamura H , Morimoto S , Shimizu T , et al. Clinical manifestations in anti-Ro52/SS-A antibody-seropositive patients with Sjögren's syndrome[J]. Immunol Med, 2021, 44 (4): 252- 262.
doi: 10.1080/25785826.2021.1919342
9 Lee YJ . Is the anti-centromere antibody a marker for a distinct subset of polyautoimmunity in Sjögren's syndrome?[J]. Korean J Intern Med, 2021, 36 (6): 1323- 1326.
doi: 10.3904/kjim.2021.467
10 中华医学会肝病学分会. 自身免疫性肝炎诊断和治疗指南(2021)[J]. 中华内科杂志, 2021, 60 (12): 1038- 1049.
doi: 10.3760/cma.j.cn112138-20211112-00796
11 中华医学会肝病学分会. 原发性胆汁性胆管炎的诊断和治疗指南(2021)[J]. 中华内科杂志, 2021, 60 (12): 1024- 1037.
doi: 10.3760/cma.j.cn112138-20211112-00794
12 中华医学会肝病学分会. 原发性硬化性胆管炎诊断及治疗指南(2021)[J]. 中华内科杂志, 2021, 60 (12): 1050- 1074.
doi: 10.3760/cma.j.cn112138-20211109-00786
13 Rubin P , Holt JF . Secretory sialography in diseases of the major salivary glands[J]. Am J Roentgenol Radium Ther Nucl Med, 1957, 77 (4): 575- 598.
14 Sun Z , Zhang Z , Fu K , et al. Diagnostic accuracy of parotid CT for identifying Sjögren's syndrome[J]. Eur J Radiol, 2012, 81 (10): 2702- 2709.
doi: 10.1016/j.ejrad.2011.12.034
15 Gamba R , Fachinetti D . From evolution to function: Two sides of the same CENP-B coin?[J]. Exp Cell Res, 2020, 390 (2): 111959.
doi: 10.1016/j.yexcr.2020.111959
16 Gelber AC , Pillemer SR , Baum BJ , et al. Distinct recognition of antibodies to centromere proteins in primary Sjögren's syndrome compared with limited scleroderma[J]. Ann Rheum Dis, 2006, 65 (8): 1028- 1032.
doi: 10.1136/ard.2005.046003
17 史洪博, 吕俊楠. 抗着丝点抗体阳性的原发干燥综合征临床及实验室特征分析[J]. 医学研究生学报, 2020, 33 (8): 839- 843.
doi: 10.16571/j.cnki.1008-8199.2020.08.011
18 颜淑敏, 曾小峰, 赵岩, 等. 抗着丝点抗体阳性原发性干燥综合征的临床特点[J]. 中华内科杂志, 2008, 47 (4): 296- 299.
doi: 10.3321/j.issn:0578-1426.2008.04.011
19 Min HK , Kim SH , Park Y , et al. Ultrasonographic characteristics of major salivary glands in anti-centromere antibody-positive primary Sjögren's syndrome[J]. PLoS One, 2021, 16 (11): e0259519.
doi: 10.1371/journal.pone.0259519
20 Lee KE , Kang JH , Lee JW , et al. Anti-centromere antibody-positive Sjögren's syndrome: A distinct clinical subgroup?[J]. Int J Rheum Dis, 2015, 18 (7): 776- 782.
doi: 10.1111/1756-185X.12684
21 Kajio N , Takeshita M , Suzuki K , et al. Anti-centromere antibo-dies target centromere-kinetochore macrocomplex: A comprehensive autoantigen profiling[J]. Ann Rheum Dis, 2021, 80 (5): 651- 659.
doi: 10.1136/annrheumdis-2020-218881
22 Seror R , Ravaud P , Bowman SJ , et al. EULAR Sjögren's syndrome disease activity index: Development of a consensus systemic disease activity index for primary Sjögren's syndrome[J]. Ann Rheum Dis, 2010, 69 (6): 1103- 1109.
doi: 10.1136/ard.2009.110619
23 Li Y , Bookman AAM . Comparison of effect on sicca symptoms of anticentromere antibody-positive Sjögren's syndrome and primary Sjögren's syndrome alone[J]. J Rheumatol, 2020, 47 (6): 876- 880.
doi: 10.3899/jrheum.190462
24 Miyawaki S , Asanuma H , Nishiyama S , et al. Clinical and serological heterogeneity in patients with anticentromere antibodies[J]. J Rheumatol, 2005, 32 (8): 1488- 1494.
25 包振英, 彭科凤, 孟彦宏, 等. 抗着丝点蛋白B抗体阳性的原发性干燥综合征的实验室特征分析[J]. 中国预防医学杂志, 2018, 19 (3): 234- 237.
doi: 10.16506/j.1009-6639.2018.03.011
26 Park Y , Lee J , Koh JH , et al. Clinical influences of anticentromere antibody on primary Sjögren's syndrome in a prospective Korean cohort[J]. Korean J Intern Med, 2021, 36 (6): 1492- 1503.
doi: 10.3904/kjim.2020.146
27 Suzuki Y , Fujii H , Nomura H , et al. Impact of double positive for anti-centromere and anti-SS-a/Ro antibodies on clinicopathological characteristics of primary Sjögren's syndrome: A retrospective cohort study[J]. Mod rheumatol, 2018, 28 (5): 872- 878.
doi: 10.1080/14397595.2017.1418164
[1] 韩艺钧,李常虹,陈秀英,赵金霞. 抗SSB抗体阳性和阴性的原发性干燥综合征患者临床及免疫学特征的比较[J]. 北京大学学报（医学版）, 2023, 55(6): 1000-1006.
[2] 张琳崎,赵静,王红彦,王宗沂,李英妮,汤稷旸,李思莹,曲进锋,赵明威. 抗ENO1抗体与狼疮性视网膜病变的相关性[J]. 北京大学学报（医学版）, 2022, 54(6): 1099-1105.
[3] 张璐,陈澄,翁梅婷,郑爱萍,苏美玲,王庆文,蔡月明. 狼疮肾炎患者肾小管间质损伤的自身抗体特征[J]. 北京大学学报（医学版）, 2022, 54(6): 1094-1098.
[4] 于昊哲,曾唯珍,吴文雨,姚中强,冯云. 原发性干燥综合征合并甲状腺功能减退眼表状态评估[J]. 北京大学学报（医学版）, 2022, 54(4): 705-711.
[5] 肖云抒,朱冯赟智,罗澜,邢晓燕,李玉慧,张学武,沈丹华. 88例重叠肌炎的临床及免疫学特征[J]. 北京大学学报（医学版）, 2021, 53(6): 1088-1093.
[6] 罗澜,邢晓燕,肖云抒,陈珂彦,朱冯赟智,张学武,李玉慧. 抗合成酶综合征合并心脏受累患者的临床及免疫学特征[J]. 北京大学学报（医学版）, 2021, 53(6): 1078-1082.
[7] 赵静,孙峰,李云,赵晓珍,徐丹,李英妮,李玉慧,孙晓麟. 抗α-1C微管蛋白抗体在系统性硬化症中的表达及临床意义[J]. 北京大学学报（医学版）, 2020, 52(6): 1009-1013.
[8] 朱冯赟智,邢晓燕,汤晓菲,李依敏,邵苗,张学武,李玉慧,孙晓麟,何菁. 肌炎合并血栓栓塞患者的临床及免疫学特征[J]. 北京大学学报（医学版）, 2020, 52(6): 995-1000.
[9] 郑艺明,郝洪军,刘怡琳,郭晶,赵亚雯,张巍,袁云. Ro52抗体与其他肌炎抗体共阳性的相关性研究[J]. 北京大学学报（医学版）, 2020, 52(6): 1088-1092.
[10] 王一帆,范稹,成姚斌,金月波,霍阳,何菁. 原发性干燥综合征患者睡眠障碍的相关影响因素[J]. 北京大学学报（医学版）, 2020, 52(6): 1063-1068.
[11] 李英妮,相晓红,赵静,李云,孙峰,王红彦,贾汝琳,胡凡磊. 抗类瓜氨酸化抗体在系统性红斑狼疮中的意义[J]. 北京大学学报（医学版）, 2019, 51(6): 1019-1024.
[12] 王永福,刘媛. 自身抗体在肿瘤及感染性疾病发生、发展中的作用[J]. 北京大学学报（医学版）, 2018, 50(6): 952-955.
[13] 刘洪江, 石连杰, 胡凡磊, 姚海红, 栗占国, 贾园. 趋化因子配体19在系统性红斑狼疮中的表达及其与B细胞异常的相关性研究[J]. 北京大学学报(医学版), 2017, 49(5): 829-834.
[14] 徐婧，刘婧，朱雷，张学武，栗占国. 葡萄糖-6-磷酸异构酶水平测定与类风湿关节炎早期诊断[J]. 北京大学学报(医学版), 2016, 48(6): 942-946.
[15] 王琳琳, 杨娜, 袁悦, 任爱国. 人叶酸受体自身抗体IgG酶联免疫吸附试验检测方法的建立及评价[J]. 北京大学学报（医学版）, 2014, 46(3): 483-487.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
ISSN 1671-167X
CN 11-4691/R
主管单位：中华人民共和国教育部
主办单位：北京大学
地址： 北京市海淀区学院路38号 北京大学医学部 《北京大学学报（医学版）》
邮编：100191
电话：010-82801551
Email： xbbjb2@bjmu.edu.cn

《北京大学学报（医学版）》
微信公众号
版权所有 © 2018 《北京大学学报（医学版）》编辑部