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

doi:10.19723/j.issn.1671-167X.2023.06.021

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

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. 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 ZHOU^3,*()

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)

摘要/Abstract

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

孟彦宏,陈怡帆,周培茹. 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[J]. 北京大学学报（医学版）, 2023, 55(6): 1088-1096.

Yan-hong MENG,Yi-fan CHEN,Pei-ru ZHOU. Clinical and immunological features of primary Sjögren's syndrome patients with positive anti-centromere protein B antibody[J]. Journal of Peking University (Health Sciences), 2023, 55(6): 1088-1096.

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参考文献 27

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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

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

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

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

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

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

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

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