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北京大学学报（医学版） ›› 2022, Vol. 54 ›› Issue (6): 1068-1073. doi: 10.19723/j.issn.1671-167X.2022.06.002

• 论著 • 上一篇    下一篇

类风湿关节炎临床分层及其特征的横断面研究

蔡文心1,李仕成2,3,刘一鸣1,4,梁如玉1,李静1,郭建萍1,胡凡磊1,孙晓麟1,李春1,刘栩1,叶华1,邓立宗3,*(),李茹1,*(),栗占国1,*()   

  1. 1. 北京大学人民医院风湿免疫科，北京 100044
    2. 苏州大学附属第二医院肿瘤科，江苏苏州 215123
    3. 中国医学科学院系统医学研究院/苏州系统医学研究所，江苏苏州 215123
    4. 郑州大学第五附属医院风湿免疫科，郑州 450052
  • 收稿日期:2022-10-10 出版日期:2022-12-18 发布日期:2022-12-19
  • 通讯作者: 邓立宗,李茹,栗占国 E-mail:denglz@ism.pumc.edu.cn;doctorliru123@163.com;zgli99@aliyun.com
  • 基金资助:
    国家自然科学基金(32141004)

A cross-sectional study on the clinical phenotypes of rheumatoid arthritis

Wen-xin CAI1,Shi-cheng LI2,3,Yi-ming LIU1,4,Ru-yu LIANG1,Jing LI1,Jian-ping GUO1,Fan-lei HU1,Xiao-lin SUN1,Chun LI1,Xu LIU1,Hua YE1,Li-zong DENG3,*(),Ru LI1,*(),Zhan-guo LI1,*()   

  1. 1. Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing 100044, China
    2. Department of Oncology, the Second Affiliated Hospital of Soochow University, Suzhou 215123, Jiangsu, China
    3. Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou Institute of Systems Medicine, Suzhou 215123, Jiangsu, China
    4. Department of Rheumatology and Immunology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
  • Received:2022-10-10 Online:2022-12-18 Published:2022-12-19
  • Contact: Li-zong DENG,Ru LI,Zhan-guo LI E-mail:denglz@ism.pumc.edu.cn;doctorliru123@163.com;zgli99@aliyun.com
  • Supported by:
    the National Natural Science Foundation of China(32141004)

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摘要：

目的: 探索类风湿关节炎(rheumatoid arthritis, RA)临床分层及其特征，为RA的发病机制、临床诊治和转归评估提供依据。方法: 选择2018—2021年于北京大学人民医院就诊的RA患者，收集患者一般情况、关节受累部位及数量、关节外表现、合并症及实验室检查结果等信息，采用统计及生物信息分析的方法，以受累关节部位、有无系统受累或合并其他自身免疫性疾病等进行临床分层，并对各亚型患者的特征进行分析。结果: 共纳入411例RA患者，平均年龄(48.84±15.17)岁，其中女性346例(84.2%)。患者被分为小关节型(74，18.0%)、全关节型(154, 37.5%)、系统型(100, 24.3%)、重叠型(83，20.2%)4个亚型。小关节型者无中大关节受累，其中35.1%有系统表现，红细胞沉降率(erythrocyte sedimentation rate, ESR)及C反应蛋白(C-reaction protein, CRP)水平和血小板计数较其他亚型低，而IgA及IgG类风湿因子阳性率较高；全关节型者中大关节和小关节均可受累，关节外表现少见，晨僵发生率和抗核抗体(antinuclear antibodies, ANA)阳性率显著低于其他亚型，而ESR及CRP水平相对较高；系统型者以合并肺间质纤维化和口、眼干燥症状常见, 病情活动指数高；重叠型至少合并另一种风湿病或自身免疫性疾病，以桥本甲状腺炎和原发性干燥综合征最为常见，与其他亚型相比，女性多见，高免疫球蛋白血症、低补体血症和斑点型ANA为其特征。结论: 根据类风湿关节炎的临床特征，可初步将其分为小关节型、全关节型、系统型、重叠型4个亚型，各有其临床和实验室特征，有助于进一步认识RA和为患者进行个体化治疗提供依据。

关键词: 类风湿关节炎, 临床分层, 聚类分析

Abstract:

Objective: To explore the characteristics and clinical phenotypes of rheumatoid arthritis (RA) and provide the basis for further understanding, interventions and outcomes of this disease. Methods: RA patients attended at Peking University People's Hospital from 2018 to 2021 were enrolled in the study. Data collection included demographic data, the sites and numbers of joints involved, extra-articular manifestations (EAM), comorbidities and laboratory variables. Statistical and bioinformatical analysis was performed to establish clinical subtypes by clustering analysis based on the type of joint involved, EAM involvement and other autoimmune diseases overlapped. The characteristics of each subtype were analyzed. Results: A total of 411 patients with RA were enrolled. The mean age was (48.84±15.17) years, and 346 (84.2%) were females. The patients were classified into 4 subtypes: small joint subtype (74, 18.0%), total joint subtype (154, 37.5%), systemic subtype (100, 24.3%), and overlapping subtype (83, 20.2%). The small joint subtype had no medium or large joint involvement, and 35.1% had systemic involvement. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and platelet count (PLT) were lower than those in other subtypes, and the rates of positive rheumatoid factors (RF-IgA and RF-IgG) were significantly higher in the small joint subtype. The total joint subtype had both large and small joint involvement but no systemic involvement. The rate of morning stiffness and positive antinuclear antibodies (ANA) in this subtype were lower than those in other subtypes. In the systemic subtype, interstitial lung disease and secondary Sj?gren syndrome were the most common systemic involvements, with prominent levels of disease activity score 28-joint count (DAS28-ESR and DAS28-CRP). The overlapping subtype was commonly combined with Hashimoto's thyroiditis or primary Sj?gren syndrome. Female in the overlapping subtype was more common than in other subtypes. This subtype was characterized by hyperglobulinemia, hypocomplementemia and high rate of positive ANA, especially spotting type. Conclusion: Based on the clinical features, RA patients could be classified into 4 subtypes: small joint subtype, total joint subtype, systemic subtype, and overlapping subtype. Each subtype had its own clinical characteristics. They help for further understanding and a more individualized treatment strategy of RA.

Key words: Rheumatoid arthritis, Clinical phenotypes, Clustering analysis

中图分类号: 

  • R593.22

图1

RA临床亚型分布图(n=411)"

表1

RA各亚型间临床特点比较"

Items Small joint subtype (n=74) Total joint subtype (n=154) Systemic subtye (n=100) Overlapping subtype (n=83) F/χ2 P value
Female, n (%) 60 (81.1) 125 (81.2) 85 (85.0) 76 (91.6) 5.034 0.169
Onset Age/years，${\bar x}$±s 47.04±18.92 47.16±13.89 44.80±13.56 45.10±17.14 0.391 0.76
Diseae duration /months, ${\bar x}$±s 140.43±103.01 142.03±109.38 209.80±143.11 116.35±111.78 1.757 0.155
Family history, n (%) 8 (10.8) 19 (12.3) 11 (11.0) 7 (8.4) 0.845 0.839
History of smoking, n (%) 12 (16.2) 26 (16.9) 15 (15.0) 10 (12.0) 1.028 0.794
Morning stiffness time＞1 h，n (%) 44 (61.1) 70 (47.0) 56 (57.1) 45 (58.4) 5.415 0.144
TJC, M (P25, P75) 3.00 (0.50，16.00) 6.00 (2.00，14.00) 14.00 (4.00，23.00) 8.50 (2.00，18.75) 27.983 ＜0.001
SJC, M (P25, P75) 4.00 (1.50，12.00) 4.50 (1.75，13.25) 6.00 (2.00，16.00) 4.00 (2.00，12.00) 4.731 0.193
DAS28-ESR， M (P25, P75) 4.30 (3.82，5.82) 4.95 (4.02，5.92) 5.41 (4.51，6.95) 5.07 (3.86，5.99) 23.880 ＜0.001
DAS28-CRP， M (P25, P75) 3.63 (2.79，5.30) 4.30 (3.32，5.44) 4.80 (3.67，6.14) 4.12 (2.99，5.66) 26.062 ＜0.001
Small joint involvement, n (%) 74 (100.0) 125 (81.2) 92 (92.0) 67 (80.7) 20.929 ＜0.001
Medium/large joint involvement, n (%) 0 (0.0) 154 (100.0) 100 (100.0) 61 (73.5) 320.682 ＜0.001
Systemic involvement, n (%) 26 (35.1) 0 (0.0) 100 (100.0) 33 (39.8) 256.091 ＜0.001
Other AID overlapped, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 83 (100.0) 411.000 ＜0.001

图2

亚型临床特征分布"

表2

RA各亚型间实验室指标比较"

Items Small joint subtype (n=74) Total joint subtype (n=154) Systemic subtye (n=100) Overlapping subtype (n=83) χ2 P value
ESR/(mm/h) 37.00 (21.50，55.00) 42.00 (25.00，74.00) 60.00 (21.00，88.00) 41.00 (25.00，66.75) 21.580 ＜0.001
CRP/(mg/L) 10.56 (2.57，30.96) 19.60 (6.30，58.59) 21.70 (5.38，53.97) 12.94 (3.06，37.39) 25.918 ＜0.001
WBC/(×109/L) 5.70 (4.25，7.30) 6.15 (4.58，8.15) 5.90 (4.20，7.20) 5.65 (4.43，6.75) 4.362 0.225
NEU/(×109/L) 3.60 (2.45，4.60) 4.15 (2.68，5.40) 3.80 (2.50，5.20) 3.35 (2.70，4.78) 4.652 0.199
LYM/(×109/L) 1.30 (0.80，1.70) 1.40 (1.00，1.83) 1.30 (1.00，1.60) 1.30 (1.00，1.70) 2.604 0.457
HGB/(g/L) 119.00 (105.50，125.50) 113.50 (102.50，123.25) 112.00 (98.00，121.00) 111.50 (98.00，121.75) 3.695 0.296
PLT/(×109/L) 207.00 (179.00，276.00) 259.00 (211.00，315.50) 249.00 (185.00，295.00) 223.50 (197.75，266.00) 25.723 ＜0.001

表3

RA各亚型间免疫学指标比较"

Items Small joint subtype (n=74) Total joint subtype (n=154) Systemic subtype (n=100) Overlapping subtype (n=83) χ2 P value
γG/TP elevation/%, M (P25, P75) 17.40 (14.90，20.80) 20.50 (16.45，23.13) 19.90 (17.10，23.20) 22.25 (17.85，25.38) 12.892 0.005
IgA elevation 8 (11.1) 25 (16.9) 21 (22.1) 13 (15.7) 3.651 0.302
IgG elevation 6 (8.3) 35 (23.6) 20 (21.1) 21 (25.3) 8.597 0.035
IgM elevation 1 (1.4) 4 (2.7) 4 (4.2) 6 (7.2) 4.379 0.223
C3 reduction 17 (23.6) 16 (10.9) 15 (15.8) 21 (25.3) 10.060 0.018
RF-IgM 62 (83.8) 108 (70.6) 74 (75.5) 64 (77.1) 4.855 0.183
RF-IgA 15 (41.7) 17 (22.4) 9 (16.1) 9 (20.9) 8.486 0.037
RF-IgG 32 (45.1) 36 (24.8) 33 (33.3) 28 (34.6) 9.182 0.027
anti-CCP 66 (90.4) 125 (82.8) 87 (87.9) 72 (87.8) 3.008 0.39
APF 50 (70.4) 89 (61.4) 69 (69.7) 50 (61.7) 3.097 0.377
anti-MCV 28 (75.7) 47 (64.4) 33 (78.6) 27 (67.5) 3.263 0.353
GPI 25 (35.2) 56 (38.6) 46 (46.5) 29 (35.8) 3.067 0.381
ANA 24 (33.8) 31 (21.2) 34 (34.7) 37 (44.6) 14.306 0.003
Homogeneous type ANA 23 (32.4) 57 (39.0) 36 (36.7) 26 (31.3) 1.786 0.618
Spotting type ANA 20 (28.2) 31 (21.2) 26 (26.5) 34 (41.0) 10.364 0.016
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ISSN 1671-167X
CN 11-4691/R
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