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北京大学学报（医学版） ›› 2019, Vol. 51 ›› Issue (3): 439-444. doi: 10.19723/j.issn.1671-167X.2019.03.010

• 论著 • 上一篇    下一篇

类风湿关节炎患者风湿病家族史特征及临床意义

张晓英1,2,*,靳家扬1,*,何菁1,甘雨舟1,陈家丽1,赵晓珍1,刘佳佳1,尤旭杰1,李雪1,郭建萍1,李小峰2,李静1,李茹1△(),栗占国1△()   

  1. 1. 北京大学人民医院风湿免疫科,风湿病机制及免疫诊断北京市重点实验室(BZ0135),北京 100044
    2. 山西医科大学第二医院风湿免疫科,太原 030001
  • 收稿日期:2019-03-15 出版日期:2019-06-18 发布日期:2019-06-26
  • 通讯作者: 张晓英,靳家扬 E-mail:doctorliru123@163.com;li99@bjmu.edu.cn
  • 作者简介:栗占国,教授,主任医师,博士生导师,北京大学人民医院临床免疫中心/风湿免疫科主任,风湿免疫研究所所长,北京大学医学部风湿免疫学系主任,北京大学临床免疫中心主任,973首席科学家,国家杰出青年科学基金获得者,CMB杰出教授及吴杨医药奖获得者,享受国务院特殊津贴。
    现任中国免疫学会临床免疫分会主任委员,中华医学会风湿病学分会名誉主任委员,国际风湿病联盟和亚太风湿病联盟前主席,WHO骨关节肌肉疾病委员会委员,Clinical Rheumatology和International Journal of Rheumatic Diseases副主编,《中华风湿病学杂志》总编,《北京大学学报(医学版)》副主编,Lancet Rheumatology、 Annals of the Rheumatic Diseases及Nature Reviews Rheumatology等期刊编委。
    长期从事风湿免疫病临床工作,主要研究方向为类风湿关节炎、系统性红斑狼疮和干燥综合征等的发病机制及免疫治疗,发现了新的致病分子及机制,建立了多种新型无创诊断和免疫治疗方法,并转化应用于临床。在Nature Medicine及Immunity等发表SCI论文240余篇,其中影响因子8.96~41.06的论文36篇。主编(译)及参编《类风湿关节炎》《风湿免疫学高级教程》等风湿病学专著30余本。
  • 基金资助:
    西藏自治区自然科学基金项目(XZ2017ZR-ZYZ02)和山西省青年科技研究基金面上项目(2015021180)

Family history of rheumatic diseases in patients with rheumatoid arthritis: a large scale cross-sectional study

Xiao-ying ZHANG1,2,*,Jia-yang JIN1,*,Jing HE1,Yu-zhou GAN1,Jia-li CHEN1,Xiao-zhen ZHAO1,Jia-jia LIU1,Xu-jie YOU1,Xue LI1,Jian-ping GUO1,Xiao-feng LI2,Jing LI1,Ru LI1△(),Zhan-guo LI1△()   

  1. 1. Department of Rheumatology and Immunology, Peking University People’s Hospital; Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis(BZ0135), Beijing 100044, China
    2. Department of Rheumatology and Immunology,Second Hospital of Shanxi Medical University, Taiyuan 030001, China
  • Received:2019-03-15 Online:2019-06-18 Published:2019-06-26
  • Contact: Xiao-ying ZHANG,Jia-yang JIN E-mail:doctorliru123@163.com;li99@bjmu.edu.cn
  • Supported by:
    Supported by Tibet Autonomous Region National Science Foundation(XZ2017ZR-ZYZ02)and General Program of Shanxi Youth Science and Technology Research Foundation (2015021180)

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摘要： 目的 分析类风湿关节炎(rheumatoid arthritis, RA)患者的风湿病家族史特征及其临床意义。方法 采用现场问卷调查方法,共调查890例RA患者,其中资料完整者803例,内容包括患者的性别、年龄、吸烟史、饮酒史、身高、体重、风湿病家族史、临床及血清学特征、疼痛和疾病总体评价、多维健康评估问卷等,并根据RA患者有无家族史进行分组比较。结果 本研究中,RA患者发病年龄为(45.09 ±14.50)岁,男女比例1 ∶3.5。有风湿病(包括RA、脊柱关节炎、干燥综合征、系统性红斑狼疮、系统性硬化症)家族史的患者123例(123/803, 15.32%), 其中一级亲属患病者占有家族史者73.98%(91/123),二级亲属患病者占有家族史者17.89%(22/123),一级+二级亲属均患病10例(8.13%)。家族史疾病种类以RA为主,为70.73%(87/123),其他风湿性疾病为21.95%(27/123),RA合并其他风湿病占7.32%(9/123)。根据有无家族史,对两组RA患者的人口学特征和临床指标进行比较,结果显示:在有家族史患者中,发病年龄提前6.04年[(39.97±13.68)岁 vs.(46.01 ±14.46)岁],类风湿因子阳性率高(78.48% vs. 66.67%), 差异具有统计学意义(P<0.05)。校正性别、体重指数及抗环瓜氨酸肽抗体等混杂因素后,有家族史患者的发病年龄提前4.54年(β = -4.54;95%CI:-8.70, -0.38;P < 0.05)。进一步分层分析发现,在吸烟RA患者中,有家族史者发病年龄提前10.02年,差异具有统计学意义(β = -10.02;95%CI:-17.60, -2.43;P = 0.01);而在不吸烟RA患者中,有家族史者发病年龄提前3.27年,差异无统计学意义(β = -3.27;95%CI:-8.37, 1.82;P= 0.21)。结论 风湿病家族史是RA发病提前的危险因素,与吸烟可能具有协同作用。

关键词: 类风湿关节炎, 家族史, 发病年龄, 吸烟

Abstract: Objective: To determine the associations between the family history of rheumatic diseases and clinical features in patients with rheumatoid arthritis (RA).Methods: In total, eight hundred and ninety patients with RA were enrolled. The demographic and clinical data were collected, including gender, age, height, body weight, age of disease onset, history of smoking and drinking, family history of rheumatic diseases, clinical and laboratory features, pain and global visual analogue scale (VAS), and multi-dimensional health assessment questionnaire (MDHAQ). Finally, 803 patients were completed the dataset and were included in the study. Results: In this cohort, the male/female ratio was 1 ∶3.5, and the age of onset was (45.09±14.50) years. A total of 123 (15.32%) patients were accompanied with family history of rheumatic diseases, including RA, spondyloarthritis, Sj?gren’s syndrome, systemic lupus erythematosus and systemic sclerosis. The percentages of first degree, second degree and both first and second degree relatives were 91 (73.98%), 22 (17.89%), and 10(8.13%) respectively. The most common disease was RA (70.73%), followed by other rheumatic diseases (21.95%), and RA combined with other rheumatic diseases (7.32%). The clinical and laboratory characteristics were compared between the patients with and without family history. The onset-age of the subjects was significantly different between those with and without family history of rheumatic diseases (39.97 ±13.68 vs. 46.01±14.46; P<0.01), which meant that the onset-age in patients with family history was 6.04 years earlier than that in patients without family history. The patients with family history had higher positive rate of rheumatoid factor (RF) compared with those without family history (78.48% vs. 66.67%, P<0.05). By adjusting with gender, body mass index (BMI), smoking and alcohol drinking, anti-cyclic citrullinated peptide (CCP) antibody and RF level, the age at disease onset in the patients with family history was 4.54 years earlier than that in the patients without family history (β=-4.54;95%CI:-8.70, -0.38;P<0.05). Further hierarchical regression analysis showed that, the age at onset of the RA patients with family history was 10.02 years earlier than that without family history among the smoking patients (β= -10.02;95%CI:-17.60, -2.43;P=0.01), while the age at onset of the RA patients with family history was 3.27 years earlier than that without family history among the never smoking patients (β=-3.27;95%CI:-8.37, 1.82;P=0.21).Conclusion: The family history of rheumatic diseases is a risk factor for early onset of RA, and may interact with smoking.

Key words: Rheumatoid arthritis, Family history, Age at onset, Smoking

中图分类号: 

  • R593.22

表1

RA患者一般情况及临床特征(n=803)"

Items Total (n=803) Family history of rheumatic disease
No (n=680) Yes (n=123) P
Female,n (%) 624 (77.71) 519 (76.32) 105 (85.37) 0.05
Han nationality,n (%) 715 (95.72) 614 (96.39) 101 (91.82) 0.03
Age/years, x?±s 55.53±13.52 56.20±13.39 51.86±13.69 <0.01
Age at RA onset/years, x?±s 45.09±14.50 46.01±14.46 39.97±13.68 <0.01
History of smoking, n (%) 222 (31.94) 185 (31.46) 37 (34.58) 0.53
History of drinking, n (%) 210 (27.23) 178 (27.30) 32 (26.89) 0.93
Disease duration/years, M (P25, P75) 7.00 (3.00,15.00) 7.00 (3.00,14.00) 10.00 (3.00, 16.00) 0.12
MDHAQ, M (P25, P75) 2.0 (0.0, 6.0) 2.0 (0.0, 6.0) 2.0 (0.0, 6.0) 0.32
Pain VAS, M (P25, P75) 3.0 (1.0, 6.0) 3.0 (1.0, 5.0) 3.0 (1.0, 6.0) 0.15
TJC,M (P25, P75) 2.0 (0.0, 6.0) 2.0 (0.0, 6.0) 2.0 (0.0, 6.0) 0.73
SJC,M (P25, P75) 1.0 (0.0, 4.0) 1.0 (0.0, 4.0) 2.0 (0.0, 4.0) 0.37
DJC,M (P25, P75) 0.0 (0.0, 4.0) 0.0 (0.0, 4.0) 1.0 (0.0,7.0) 0.15
BMI/(kg/m2), x?±s 23.22±3.50 23.35±3.47 22.47±3.61 0.05
CRP/(mg/L),M (P25, P75) 4.68 (1.85, 11.72) 4.88 (2.00, 12.03) 3.40 (1.53, 10.54) 0.07
ESR/(mm/h), M (P25, P75) 19.0 (10.0, 37.8) 19.0 (11.0, 39.0) 17.0 (8.3, 29.5) 0.05
DAS28-CRP,M (P25, P75) 3.1 (2.2, 4.1) 3.0 (2.2, 4.1) 3.1 (2.1, 4.2) 0.96
DAS28-ESR,M (P25, P75) 3.6 (2.7, 4.7) 3.6 (2.7, 4.7) 3.3 (2.5, 4.5) 0.17
Anti-CCP positive, n (%) 509 (85.55) 441 (85.96) 68 (82.93) 0.47
RF-positive, n (%) 394 (68.28) 332 (66.67) 62 (78.48) <0.05

表2

RA患者风湿病家族史分布特征(n=123)"

Relatives RA SpA SS SLE SSc RA with others Total, n (%)
First-degree relatives 70 6 5 5 1 4 91 (73.98)
Second-degree relatives 15 4 2 1 0 0 22 (17.89)
First- and second-degree relatives 2 1 1 1 0 5 10 (8.13)
Total, n (%) 87(70.73) 11 (8.94) 8 (6.51) 7 (5.69) 1(0.81) 9 (7.32) 123 (100.00)

表3

应用广义线性回归模型分析家族史对RA患者发病年龄的影响"

Items β(95%CI) P
Non-adjusted -6.04 (-8.79, -3.28) <0.01
Adjusted -4.54 (-8.70, -0.38) <0.05

表4

RA发病年龄的危险因素分层及与家族史交互作用分析"

Variable n β (95%CI) P (β) P (interaction)
Gender 0.20
Male 179 1.81(-8.81, 12.43) 0.74
Female 624 -6.78(-11.37, -2.20) <0.01
Nation 0.96
Han 715 -5.42(-9.71, -1.13) 0.01
Minority 32 -10.29(-39.73, 19.14) 0.51
Drinking 0.10
No 561 -7.32(-12.13, -2.51) <0.01
Yes 210 0.89(-7.88, 9.66) 0.84
Smoking 0.09
No 473 -3.27(-8.37, 1.82) 0.21
Yes 222 -10.02(-17.60, -2.43) 0.01
BMI/(kg/m2) 0.12
<24 337 -8.83(-14.66, -3.00) <0.01
24-28 145 -2.81(-9.87, 4.25) 0.44
>28 80 1.11(-10.52, 12.74) 0.85
RF 0.79
Negative 183 -5.10(-14.20, 4.00) 0.27
Positive 394 -5.78(-10.52, -1.03) <0.05
Anti-CCP 0.56
Negative 86 -8.92(-20.83, 2.98) 0.15
Positive 509 -4.75(-9.31, -0.19) <0.05
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