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Article(id=1194617493298843957, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1194617490446721194, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.1097.2024.1113, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1692288000000, receivedDateStr=2023-08-18, revisedDate=null, revisedDateStr=null, acceptedDate=1699372800000, acceptedDateStr=2023-11-08, onlineDate=1762748605322, onlineDateStr=2025-11-10, pubDate=1740672000000, pubDateStr=2025-02-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1762748605322, onlineIssueDateStr=2025-11-10, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1762748605322, creator=13701087609, updateTime=1762748605322, updator=13701087609, issue=Issue{id=1194617490446721194, tenantId=1146029695717560320, journalId=1189873630562394117, year='2025', volume='50', issue='2', pageStart='123', pageEnd='244', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1762748604641, creator=13701087609, updateTime=1762749162199, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1194619829073191185, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1194617490446721194, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1194619829073191186, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1194617490446721194, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=146, endPage=153, ext={EN=ArticleExt(id=1194617493579862328, articleId=1194617493298843957, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Analysis of factors affecting rheumatoid-interstitial pulmonary diseases: a study based on an analysis of latent class, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To analyze the classification characteristics of rheumatoid arthritis (RA)-related antibodies and to investigate the factors influencing the development of RA-related interstitial pulmonary diseases (RA-ILD) in RA patients using latent class analysis (LCA). Methods A retrospective analysis of 712 RA patients treated at the Department of Rheumatology and Immunology of the Second Hospital of Shanxi Medical University from December 2019 to October 2022 was conducted. According to whether patients had RA-ILD or not, they were divided into simple RA group (n=523) and RA-ILD group (n=189). Then, the differences in general data, clinical features, medication use and laboratory indicators were compared between the two groups. Based on the differences in RA-related antibody indicators, 712 patients were divided into 3 latent categories using LCA: high-risk group (n=364), medium-risk group (n=205), and low-risk group (n=143).One-way analysis of variance was employed to compare clinical characteristics of the 3 groups, and the prevalence of RA-ILD was calculated. Multivariate logistic regression analysis was utilized to identify independent affect factors of RA-ILD. Results Significant differences in gender, age, and smoking history were observed between simple RA group and RA-ILD group (P<0.05). The high, medium and low risk groups exhibited significant differences in gender, age, prednisone (PRED) and methotrexate (MTX) medication history, Red blood cell count (RBC), interleukin-2 (IL-2), IL-4, IL-10, IL-17, TNF-α, interferon-γ (INF-γ), serum globulins, and white blood albumins (P<0.05). The high-risk group had a higher proportion of males, RBC, IL-2, IL-4, IL-10, IL-17, TNF-α, INF-γ, and serum globulin levels, and a lower proportion of MTX medication compared with medium- and low-risk groups (P<0.05 or P<0.01). The medium-risk group had a higher proportion of MTX administration than that in high- and low-risk groups (P<0.05 or P<0.01). The low-risk group had a higher proportion of females and older age than those in other two groups (P<0.05 or P<0.01). The prevalence of RA-ILD was 30.5%, 23.9% and 20.3% in the three groups, respectively. Multivariate logistic regression analysis indicated that male (OR=2.920, 95%CI 1.722-4.952), age (OR=1.055, 95%CI 1.035-1.074), IL-17 (OR=1.013, 95%CI 1.003-1.023), TNF-α (OR=1.050, 95%CI 1.017-1.083), INF-γ (OR=0.962, 95%CI 0.932-0.993), Serum albumin (OR=0.919, 95%CI 0.869-0.971) and high risk antibody indicators (OR=1.725, 95%CI 1.084-2.745) were independent predictors for RA-ILD. Conclusions RA patients exhibit distinct categories of antibody indicators, with a higher prevalence in high-risk patients with RA-ILD. RA-ILD is more likely to occur in male, elderly patients with abnormal liver function and high-risk antibody indictors. More attention should be paid to these patients and individualized interventions should be developed and implemented in a timely manner to improve the quality of patient survival.

, correspAuthors=Xiao-Xia Wang, Li-Xia Qiu, authorNote=null, correspAuthorsNote=
Wang Xiao-Xia, E-mail:
Qiu Li-Xia, E-mail:
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目的 利用潜在类别分析(LCA)法分析类风湿关节炎(RA)患者RA相关抗体的分类特征，并探讨RA患者发生类风湿关节炎相关间质性肺疾病(RA-ILD)的影响因素。方法 收集2019年12月－2022年10月山西医科大学第二医院风湿免疫科收治的712例RA患者进行回顾性分析；根据是否发生RA-ILD将其分为单纯RA组(n=523例)与RA-ILD组(n=189)，比较两组患者一般资料、临床特征、用药情况及实验室指标的差异。根据RA相关抗体指标的不同，采用LCA法将712例患者分为3个潜在类别：抗体指标高危组(n=364例)、抗体指标中危组(n=205例)及抗体指标低危组(n=143例)。采用单因素方差分析比较3组的临床特征，并计算RA-ILD的患病率；采用多因素logistic回归分析RA-ILD发生的独立影响因素。结果 单纯RA组与RA-ILD组在性别、年龄、吸烟史等方面差异有统计学意义(P<0.05)。抗体指标高、中、低危组在性别、年龄、醋酸泼尼松(PRED)及甲氨蝶呤(MTX)用药史、红细胞计数(RBC)、白细胞介素(IL)-2、IL-4、IL-10、IL-17、肿瘤坏死因子-α(TNF-α)、γ干扰素(INF-γ)、血清球蛋白、血清白蛋白水平方面差异有统计学意义(P<0.05)。其中，抗体指标高危组的男性占比、RBC、IL-2、IL-4、IL-10、IL-17、TNF-α、INF-γ、血清球蛋白水平等均高于抗体指标中、低危组，MTX用药比例低于抗体指标中危组，差异均有统计学意义(P<0.05或P<0.01)；抗体指标中危组的MTX用药比例高于抗体指标高危组及低危组，差异有统计学意义(P<0.05或P<0.01)；抗体指标低危组的女性占比、年龄等高于其他两组，差异有统计学意义(P<0.05或P<0.01)。3组RA-ILD的患病率分别为30.5%、23.9%、20.3%，差异有统计学意义(χ2=6.525，P=0.038)。多因素logistic回归分析结果显示，男性(OR=2.920，95%CI 1.722~4.952)、年龄(OR=1.055，95%CI 1.035~1.074)、IL-17(OR=1.013，95%CI 1.003~1.023)、TNF-α(OR=1.050，95%CI 1.017~1.083)、INF-γ(OR=0.962，95%CI 0.932~0.993)、血清白蛋白(OR=0.919，95%CI 0.869~0.971)、抗体指标高危(OR=1.725，95%CI 1.084~2.745)是RA患者并发ILD的独立影响因素。结论 RA患者抗体指标有明显的分类特征，抗体指标高危者RA-ILD患病率较高。男性、高龄、肝功能异常、细胞因子异常及抗体指标高危的患者更易发生RA-ILD，应及时制定并实施个体化干预措施，以提高患者的生存质量。

, correspAuthors=王晓霞, 仇丽霞, authorNote=null, correspAuthorsNote=
王晓霞，E-mail：
仇丽霞，E-mail：
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聂艳聪，硕士研究生，主要从事卫生统计方面的研究

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聂艳聪，硕士研究生，主要从事卫生统计方面的研究

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聂艳聪，硕士研究生，主要从事卫生统计方面的研究

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keyword=interstitial pulmonary diseases), Keyword(id=1194646510865453857, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493298843957, language=CN, orderNo=1, keyword=类风湿关节炎), Keyword(id=1194646510919979810, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493298843957, language=CN, orderNo=2, keyword=潜在类别分析), Keyword(id=1194646511016448803, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493298843957, language=CN, orderNo=3, keyword=间质性肺疾病)], refs=[Reference(id=1194646513415590706, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493298843957, doi=null, pmid=null, pmcid=null, year=2020, volume=164, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[1], rfOrder=0, authorNames=Osipova D, Janssen R, Martens HA, journalName=Ned Tijdschr Geneeskd, refType=null, unstructuredReference=Osipova D, Janssen R, Martens HA. 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RF. 类风湿因子；APF. 抗核周因子；AKA. 抗角蛋白抗体；ANA. 抗核抗体；CCP. 环瓜氨酸多肽；AFA家族. 抗聚丝蛋白抗体

, figureFileSmall=0vmjqg9KQacSyIZN9wsG4A==, figureFileBig=iOPKwFFDo1X4CFSaUCGkQQ==, tableContent=null), ArticleFig(id=1194646512396374822, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493298843957, language=EN, label=Tab.1, caption=

Autoantibody indicator assignment table

, figureFileSmall=null, figureFileBig=null, tableContent=
自身抗体赋值
RF-IgA0~18 U/ml=0, >18 U/ml=1
RF-IgG0~18 U/ml=0, >18 U/ml=1
RF-IgM0~18 U/ml=0, >18 U/ml=1
APF<1:20=0, ≥1:20=1
AKA<1:10=0, ≥1:10=1
ANA<1:80=0, ≥1:80=1
CCP<20 U/ml=0, ≥20 U/ml=1
AFA家族<20 U/ml=0, ≥20 U/ml=1
抗RA33<25 U/ml=0, ≥25 U/ml=1
), ArticleFig(id=1194646512463483687, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493298843957, language=CN, label=表1, caption=

自身抗体指标赋值表

, figureFileSmall=null, figureFileBig=null, tableContent=
自身抗体赋值
RF-IgA0~18 U/ml=0, >18 U/ml=1
RF-IgG0~18 U/ml=0, >18 U/ml=1
RF-IgM0~18 U/ml=0, >18 U/ml=1
APF<1:20=0, ≥1:20=1
AKA<1:10=0, ≥1:10=1
ANA<1:80=0, ≥1:80=1
CCP<20 U/ml=0, ≥20 U/ml=1
AFA家族<20 U/ml=0, ≥20 U/ml=1
抗RA33<25 U/ml=0, ≥25 U/ml=1
), ArticleFig(id=1194646512534786856, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493298843957, language=EN, label=Tab.2, caption=

Comparison of baseline characteristics between two groups of patients with RA

, figureFileSmall=null, figureFileBig=null, tableContent=
项目单纯RA组(n=523)RA-ILD组(n=189)χ2/t/ZP
一般资料
性别48.077<0.001
男[例(%)]117(22.4)93(49.2)
女[例(%)]406(77.6)96(50.8)
年龄(岁, $\bar{x}±s$)53.1±12.660.7±10.7-7.959<0.001
BMI(kg/m2, $\bar{x}±s$)23.8±11.323.4±3.70.5210.602
病程(年, M(Q1, Q3)4.0(1.0, 10.0)5.0(1.0, 12.0)-1.2260.221
吸烟史[例(%)]92(17.6)72(38.1)32.924<0.001
饮酒史[例(%)]51(9.75)36(19.0)11.185<0.001
高血压史[例(%)]126(24.1)46(24.3)0.0050.946
糖尿病史[例(%)]43(8.2)19(10.1)0.5860.444
临床特征
晨僵时间(min, $\bar{x}±s$)59.2±46.260.8±58.6-0.4040.686
肿胀关节数(个, $\bar{x}±s$)14.8±9.616.3±9.9-1.7260.085
疼痛关节数(个, $\bar{x}±s$)16.8±9.218.7±9.0-2.5720.010
用药史[例(%)]
PRED383(73.2)152(80.4)3.8440.050
MTX130(24.9)36(19.0)2.6200.106
LEF171(32.7)70(37.0)1.1680.280
血常规
RBC[×1012/L, M(Q1, Q3)]4.2(3.8, 4.5)4.2(3.8, 4.5)-0.1470.883
HG[g/L, M(Q1, Q3)]122.0(110.0, 133.0)123.0(110.0, 134.0)-0.8480.397
PLT[×109/L, M(Q1, Q3)]281.0(226.0, 340.0)292.0(222.5, 352.0)-1.2040.229
WBC[×109/L, M(Q1, Q3)]6.4(5.2, 7.8)7.2(5.7, 8.7)-3.919<0.001
炎性标志物
ESR[mm/h, M(Q1, Q3)]42.0(20.0, 74.0)52.0(24.5, 84.5)-2.6420.008
CRP[mg/L, M(Q1, Q3)]15.3(4.2, 40.9)19.4(5.5, 52.0)-2.2920.022
细胞因子[pg/ml, M(Q1, Q3)]
IL-23.1(2.0, 4.6)3.7(2.3, 5.9)-3.2480.001
IL-43.2(2.0, 5.1)3.5(2.2, 7.4)-2.4400.015
IL-616.1(7.4, 41.6)16.9(7.8, 48.9)-0.5880.557
IL-105.0(3.5, 7.1)6.0(4.2, 9.4)-3.539<0.001
IL-179.4(4.6, 17.9)13.0(6.1, 25.4)-3.4420.001
TNF-α4.6(2.7, 8.9)8.1(3.0, 15.0)-3.916<0.001
INF-γ4.2(2.7, 6.6)4.9(3.3, 9.6)-3.3550.001
肝功能
血清总蛋白[g/L, M(Q1, Q3)]68.1(64.2, 73.0)66.3(61.6, 71.0)-3.539<0.001
血清球蛋白[g/L, M(Q1, Q3)]32.2(28.1, 35.9)32.1(29.0, 36.8)-0.5820.561
血清白蛋白($\bar{x}±s$, g/L)36.1±4.434.0±4.45.692<0.001
自身抗体[例(%)]
RF-IgA73(14.0)19(10.1)1.8820.170
RF-IgG160(30.6)54(28.6)0.2700.603
RF-IgM31(5.9)7(3.7)1.3590.244
APF289(55.3)125(66.1)6.7520.009
AKA299(57.2)124(65.6)4.0990.043
ANA262(50.1)95(50.3)0.0020.968
CCP435(83.2)166(87.8)2.2880.130
AFA家族387(74.0)158(83.6)7.1290.008
抗RA3355(10.5)21(11.1)0.0520.820
), ArticleFig(id=1194646512610284329, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493298843957, language=CN, label=表2, caption=

两组RA患者的基线特征比较

, figureFileSmall=null, figureFileBig=null, tableContent=
项目单纯RA组(n=523)RA-ILD组(n=189)χ2/t/ZP
一般资料
性别48.077<0.001
男[例(%)]117(22.4)93(49.2)
女[例(%)]406(77.6)96(50.8)
年龄(岁, $\bar{x}±s$)53.1±12.660.7±10.7-7.959<0.001
BMI(kg/m2, $\bar{x}±s$)23.8±11.323.4±3.70.5210.602
病程(年, M(Q1, Q3)4.0(1.0, 10.0)5.0(1.0, 12.0)-1.2260.221
吸烟史[例(%)]92(17.6)72(38.1)32.924<0.001
饮酒史[例(%)]51(9.75)36(19.0)11.185<0.001
高血压史[例(%)]126(24.1)46(24.3)0.0050.946
糖尿病史[例(%)]43(8.2)19(10.1)0.5860.444
临床特征
晨僵时间(min, $\bar{x}±s$)59.2±46.260.8±58.6-0.4040.686
肿胀关节数(个, $\bar{x}±s$)14.8±9.616.3±9.9-1.7260.085
疼痛关节数(个, $\bar{x}±s$)16.8±9.218.7±9.0-2.5720.010
用药史[例(%)]
PRED383(73.2)152(80.4)3.8440.050
MTX130(24.9)36(19.0)2.6200.106
LEF171(32.7)70(37.0)1.1680.280
血常规
RBC[×1012/L, M(Q1, Q3)]4.2(3.8, 4.5)4.2(3.8, 4.5)-0.1470.883
HG[g/L, M(Q1, Q3)]122.0(110.0, 133.0)123.0(110.0, 134.0)-0.8480.397
PLT[×109/L, M(Q1, Q3)]281.0(226.0, 340.0)292.0(222.5, 352.0)-1.2040.229
WBC[×109/L, M(Q1, Q3)]6.4(5.2, 7.8)7.2(5.7, 8.7)-3.919<0.001
炎性标志物
ESR[mm/h, M(Q1, Q3)]42.0(20.0, 74.0)52.0(24.5, 84.5)-2.6420.008
CRP[mg/L, M(Q1, Q3)]15.3(4.2, 40.9)19.4(5.5, 52.0)-2.2920.022
细胞因子[pg/ml, M(Q1, Q3)]
IL-23.1(2.0, 4.6)3.7(2.3, 5.9)-3.2480.001
IL-43.2(2.0, 5.1)3.5(2.2, 7.4)-2.4400.015
IL-616.1(7.4, 41.6)16.9(7.8, 48.9)-0.5880.557
IL-105.0(3.5, 7.1)6.0(4.2, 9.4)-3.539<0.001
IL-179.4(4.6, 17.9)13.0(6.1, 25.4)-3.4420.001
TNF-α4.6(2.7, 8.9)8.1(3.0, 15.0)-3.916<0.001
INF-γ4.2(2.7, 6.6)4.9(3.3, 9.6)-3.3550.001
肝功能
血清总蛋白[g/L, M(Q1, Q3)]68.1(64.2, 73.0)66.3(61.6, 71.0)-3.539<0.001
血清球蛋白[g/L, M(Q1, Q3)]32.2(28.1, 35.9)32.1(29.0, 36.8)-0.5820.561
血清白蛋白($\bar{x}±s$, g/L)36.1±4.434.0±4.45.692<0.001
自身抗体[例(%)]
RF-IgA73(14.0)19(10.1)1.8820.170
RF-IgG160(30.6)54(28.6)0.2700.603
RF-IgM31(5.9)7(3.7)1.3590.244
APF289(55.3)125(66.1)6.7520.009
AKA299(57.2)124(65.6)4.0990.043
ANA262(50.1)95(50.3)0.0020.968
CCP435(83.2)166(87.8)2.2880.130
AFA家族387(74.0)158(83.6)7.1290.008
抗RA3355(10.5)21(11.1)0.0520.820
), ArticleFig(id=1194646512698364714, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493298843957, language=EN, label=Tab.3, caption=

Evaluation indicators for each latent class model

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模型AICBICaBICEntropyLMRTBLRT类别概率
Class 16525.706566.816538.23----
Class 25554.645641.435581.100.880<0.001<0.0010.62/0.38
Class 35461.445593.925501.830.825<0.001<0.0010.51/0.29/0.20
Class 45439.055617.205493.370.7910.0415<0.0010.29/0.20/0.44/0.07
Class 55430.175654.005498.410.8200.1277<0.0010.18/0.02/0.07/0.29/0.44
Class 65440.515710.035522.690.8180.14341.00000.44/0.03/0.03/0.14/0.07/0.29
Class 75443.625758.825539.730.8360.37891.00000.17/013/0.02/0.08/0.04/0.49/0.07
), ArticleFig(id=1194646512765473579, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493298843957, language=CN, label=表3, caption=

各潜在类别模型的评价指标

, figureFileSmall=null, figureFileBig=null, tableContent=
模型AICBICaBICEntropyLMRTBLRT类别概率
Class 16525.706566.816538.23----
Class 25554.645641.435581.100.880<0.001<0.0010.62/0.38
Class 35461.445593.925501.830.825<0.001<0.0010.51/0.29/0.20
Class 45439.055617.205493.370.7910.0415<0.0010.29/0.20/0.44/0.07
Class 55430.175654.005498.410.8200.1277<0.0010.18/0.02/0.07/0.29/0.44
Class 65440.515710.035522.690.8180.14341.00000.44/0.03/0.03/0.14/0.07/0.29
Class 75443.625758.825539.730.8360.37891.00000.17/013/0.02/0.08/0.04/0.49/0.07
), ArticleFig(id=1194646512836776748, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493298843957, language=EN, label=Tab.4, caption=

Comparison of baseline data between the three groups of rheumatoid arthritis patients

, figureFileSmall=null, figureFileBig=null, tableContent=
项目抗体指标低危组(n=143)抗体指标中危组(n=205)抗体指标高危组(n=364)χ2/F/ZP
一般资料
性别[例(%)]8.1210.017
男32(22.4)54(26.3)124(34.1)(1)
女111(77.6)151(73.7)240(65.9)(1)
年龄(岁, $\bar{x}±s$)55.9±13.553.2±13.6(1)55.8±11.4(2)3.2190.041
BMI(kg/m2, $\bar{x}±s$)23.6±3.323.2±4.024.0±13.40.4230.655
病程(年, $\bar{x}±s$)7.5±8.77.4 ±8.17.8±9.10.1170.890
吸烟史[例(%)]28(19.6)43(21.0)93(25.5)2.7510.253
饮酒史[例(%)]16(11.2)24(11.7)47(12.9)0.3550.838
高血压史[例(%)]43(30.1)47(22.9)82(22.5)3.4260.180
糖尿病史[例(%)]14(9.8)18(8.8)30(8.2)0.3120.856
临床特征
晨僵时间(分, $\bar{x}±s$)61.1±53.558.2±44.259.9±45.50.1750.840
肿胀关节数(个, $\bar{x}±s$)15.2±10.114.9±9.515.4±9.80.1490.861
疼痛关节数(个, $\bar{x}±s$)17.2±9.416.6±9.317.7±9.00.8360.434
用药史
PRED[例(%)]115(80.4)141(68.8)(1)279(76.6)(2)7.0160.030
MTX[例(%)]37(25.9)60(29.3)69(19.0)(2)8.4560.015
LEF[例(%)]40(28.0)68(33.2)133(36.5)3.4240.181
血常规
RBC[×1012/L, M(Q1, Q3)]4.1(3.8, 4.4)4.1(3.8, 4.5)4.3(3.9, 4.6)(1)8.4440.015
HG[g/L, M(Q1, Q3)]122.0(108.0, 132.0)120.0(107.5, 132.0)123.0(111.0, 134.0)3.8490.146
PLT[×109/L, M(Q1, Q3)]290.0(220.0, 360.0)274.0(230.0, 356.0)284.0(222.3, 332.0)0.5010.778
WBC[×109/L, M(Q1, Q3)]6.5(5.4, 8.3)6.2(5.1, 8.1)6.6(5.4, 8.1)1.9320.381
炎性标志物
ESR[mm/H, M(Q1, Q3)]36.0(15.0, 75.0)43.0(21.0, 75.0)50.0(24.0, 80.0)5.3830.068
CRP[mg/L, M(Q1, Q3)]16.2(4.1, 53.8)16.1(3.9, 36.3)16.6(4.6, 44.4)1.5540.460
细胞因子
IL-2[pg/ml, M(Q1, Q3)]2.4(1.5, 3.9)3.2(2.1, 4.5)(1)3.6(2.3, 5.8)(1)(2)37.819<0.001
IL-4[pg/ml, M(Q1, Q3)]2.5(1.8, 3.5)3.5(2.1, 5.4)(1)3.7(2.3, 7.1)(1)33.205<0.001
IL-6[pg/ml, M(Q1, Q3)]14.5(5.6, 42.3)16.0(8.1, 44.3)17.8(7.9, 44.4)1.5440.462
IL-10[pg/ml, M(Q1, Q3)]4.5(3.2, 6.5)5.0(3.5, 7.3)5.6(4.0, 8.7)(1)16.969<0.001
IL-17[pg/ml, M(Q1, Q3)]7.2(4.2, 12.6)9.2(3.3, 19.1)12.2(6.3, 24.0)(1)(2)35.567<0.001
TNF-α[pg/ml, M(Q1, Q3)]3.1(1.9, 5.2)4.9(2.8, 9.4)(1)6.9(3.4, 12.3)(1)(2)52.461<0.001
INF-γ[pg/ml, M(Q1, Q3)]3.7(2.5, 5.6)4.4(2.8, 6.7)(1)4.6(3.1, 8.2)(1)19.533<0.001
肝功能
血清总蛋白[g/L, M(Q1, Q3)]67.4(63.6, 71.6)67.7(64.0, 71.7)67.6(63.8, 73.2)0.1600.923
血清球蛋白[g/L, M(Q1, Q3)]31.7(27.5, 35.0)31.9(27.9, 35.5)32.5(28.9, 36.8)(1)6.8930.032
血清白蛋白(g/L, $\bar{x}±s$)36.3±4.0735.7±4.635.2±4.5(1)3.5050.031
), ArticleFig(id=1194646512929051437, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493298843957, language=CN, label=表4, caption=

3组类风湿关节炎(RA)患者基线数据比较

, figureFileSmall=null, figureFileBig=null, tableContent=
项目抗体指标低危组(n=143)抗体指标中危组(n=205)抗体指标高危组(n=364)χ2/F/ZP
一般资料
性别[例(%)]8.1210.017
男32(22.4)54(26.3)124(34.1)(1)
女111(77.6)151(73.7)240(65.9)(1)
年龄(岁, $\bar{x}±s$)55.9±13.553.2±13.6(1)55.8±11.4(2)3.2190.041
BMI(kg/m2, $\bar{x}±s$)23.6±3.323.2±4.024.0±13.40.4230.655
病程(年, $\bar{x}±s$)7.5±8.77.4 ±8.17.8±9.10.1170.890
吸烟史[例(%)]28(19.6)43(21.0)93(25.5)2.7510.253
饮酒史[例(%)]16(11.2)24(11.7)47(12.9)0.3550.838
高血压史[例(%)]43(30.1)47(22.9)82(22.5)3.4260.180
糖尿病史[例(%)]14(9.8)18(8.8)30(8.2)0.3120.856
临床特征
晨僵时间(分, $\bar{x}±s$)61.1±53.558.2±44.259.9±45.50.1750.840
肿胀关节数(个, $\bar{x}±s$)15.2±10.114.9±9.515.4±9.80.1490.861
疼痛关节数(个, $\bar{x}±s$)17.2±9.416.6±9.317.7±9.00.8360.434
用药史
PRED[例(%)]115(80.4)141(68.8)(1)279(76.6)(2)7.0160.030
MTX[例(%)]37(25.9)60(29.3)69(19.0)(2)8.4560.015
LEF[例(%)]40(28.0)68(33.2)133(36.5)3.4240.181
血常规
RBC[×1012/L, M(Q1, Q3)]4.1(3.8, 4.4)4.1(3.8, 4.5)4.3(3.9, 4.6)(1)8.4440.015
HG[g/L, M(Q1, Q3)]122.0(108.0, 132.0)120.0(107.5, 132.0)123.0(111.0, 134.0)3.8490.146
PLT[×109/L, M(Q1, Q3)]290.0(220.0, 360.0)274.0(230.0, 356.0)284.0(222.3, 332.0)0.5010.778
WBC[×109/L, M(Q1, Q3)]6.5(5.4, 8.3)6.2(5.1, 8.1)6.6(5.4, 8.1)1.9320.381
炎性标志物
ESR[mm/H, M(Q1, Q3)]36.0(15.0, 75.0)43.0(21.0, 75.0)50.0(24.0, 80.0)5.3830.068
CRP[mg/L, M(Q1, Q3)]16.2(4.1, 53.8)16.1(3.9, 36.3)16.6(4.6, 44.4)1.5540.460
细胞因子
IL-2[pg/ml, M(Q1, Q3)]2.4(1.5, 3.9)3.2(2.1, 4.5)(1)3.6(2.3, 5.8)(1)(2)37.819<0.001
IL-4[pg/ml, M(Q1, Q3)]2.5(1.8, 3.5)3.5(2.1, 5.4)(1)3.7(2.3, 7.1)(1)33.205<0.001
IL-6[pg/ml, M(Q1, Q3)]14.5(5.6, 42.3)16.0(8.1, 44.3)17.8(7.9, 44.4)1.5440.462
IL-10[pg/ml, M(Q1, Q3)]4.5(3.2, 6.5)5.0(3.5, 7.3)5.6(4.0, 8.7)(1)16.969<0.001
IL-17[pg/ml, M(Q1, Q3)]7.2(4.2, 12.6)9.2(3.3, 19.1)12.2(6.3, 24.0)(1)(2)35.567<0.001
TNF-α[pg/ml, M(Q1, Q3)]3.1(1.9, 5.2)4.9(2.8, 9.4)(1)6.9(3.4, 12.3)(1)(2)52.461<0.001
INF-γ[pg/ml, M(Q1, Q3)]3.7(2.5, 5.6)4.4(2.8, 6.7)(1)4.6(3.1, 8.2)(1)19.533<0.001
肝功能
血清总蛋白[g/L, M(Q1, Q3)]67.4(63.6, 71.6)67.7(64.0, 71.7)67.6(63.8, 73.2)0.1600.923
血清球蛋白[g/L, M(Q1, Q3)]31.7(27.5, 35.0)31.9(27.9, 35.5)32.5(28.9, 36.8)(1)6.8930.032
血清白蛋白(g/L, $\bar{x}±s$)36.3±4.0735.7±4.635.2±4.5(1)3.5050.031
), ArticleFig(id=1194646513033909038, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493298843957, language=EN, label=Tab.5, caption=

Prevalence rate of RA-ILD in low, medium and high risk groups

, figureFileSmall=null, figureFileBig=null, tableContent=
潜在类别人群RA-ILD(例)合计患病率(%)
未发生发生
合计52318971226.5
抗体指标低危组1142914320.3
抗体指标中危组1564920523.9
抗体指标高危组25311136430.5(1)(2)
), ArticleFig(id=1194646513084240687, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493298843957, language=CN, label=表5, caption=

抗体指标低、中、高危3组人群的RA-ILD患病率比较

, figureFileSmall=null, figureFileBig=null, tableContent=
潜在类别人群RA-ILD(例)合计患病率(%)
未发生发生
合计52318971226.5
抗体指标低危组1142914320.3
抗体指标中危组1564920523.9
抗体指标高危组25311136430.5(1)(2)
), ArticleFig(id=1194646513155543856, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493298843957, language=EN, label=Tab.6, caption=

Results of multivariate logistic regression analysis

, figureFileSmall=null, figureFileBig=null, tableContent=
变量βSEWald χ2OR(95%CI)P
男性1.0720.26915.8122.920(1.722~4.952)<0.001
年龄0.0530.00931.7481.055(1.035~1.074)<0.001
IL-170.0130.0056.0381.013(1.003~1.023)0.014
TNF-α0.0480.0169.1811.050(1.017~1.083)0.002
INF-γ-0.0390.0165.7420.962(0.932~ 0.993)0.017
血清白蛋白-0.0850.0289.0510.919(0.869~ 0.971)0.003
抗体指标高危0.5450.2375.2841.725(1.084~2.745)0.022
), ArticleFig(id=1194646513243624241, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493298843957, language=CN, label=表6, caption=

多因素logistic回归分析结果

, figureFileSmall=null, figureFileBig=null, tableContent=
变量βSEWald χ2OR(95%CI)P
男性1.0720.26915.8122.920(1.722~4.952)<0.001
年龄0.0530.00931.7481.055(1.035~1.074)<0.001
IL-170.0130.0056.0381.013(1.003~1.023)0.014
TNF-α0.0480.0169.1811.050(1.017~1.083)0.002
INF-γ-0.0390.0165.7420.962(0.932~ 0.993)0.017
血清白蛋白-0.0850.0289.0510.919(0.869~ 0.971)0.003
抗体指标高危0.5450.2375.2841.725(1.084~2.745)0.022
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类风湿关节炎相关间质性肺疾病的影响因素分析：一项基于潜在类别分析的研究
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聂艳聪 1 , 尹梅林 2 , 王晓霞 3, * , 仇丽霞 1, *
解放军医学杂志 | 临床研究 2025,50(2): 146-153
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解放军医学杂志 | 临床研究 2025, 50(2): 146-153
类风湿关节炎相关间质性肺疾病的影响因素分析：一项基于潜在类别分析的研究
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聂艳聪1, 尹梅林2, 王晓霞3, * , 仇丽霞1, *
作者信息
  • 1山西医科大学公共卫生学院，山西太原 030000
  • 2山西医科大学第二临床医学院，山西太原 030000
  • 3山西医科大学第二医院风湿免疫科，山西太原 030000

    • 聂艳聪，硕士研究生，主要从事卫生统计方面的研究

通讯作者:

王晓霞，E-mail：
仇丽霞，E-mail：
Analysis of factors affecting rheumatoid-interstitial pulmonary diseases: a study based on an analysis of latent class
Yan-Cong Nie1, Mei-Lin Yin2, Xiao-Xia Wang3, * , Li-Xia Qiu1, *
Affiliations
  • 1School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030000, China
  • 2Second Clinical School of Shanxi Medical University, Taiyuan, Shanxi 030000, China
  • 3Department of Rheumatology and Immunology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030000, China
出版时间: 2025-02-28 doi: 10.11855/j.issn.0577-7402.1097.2024.1113
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摘要
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目的 利用潜在类别分析(LCA)法分析类风湿关节炎(RA)患者RA相关抗体的分类特征，并探讨RA患者发生类风湿关节炎相关间质性肺疾病(RA-ILD)的影响因素。方法 收集2019年12月－2022年10月山西医科大学第二医院风湿免疫科收治的712例RA患者进行回顾性分析；根据是否发生RA-ILD将其分为单纯RA组(n=523例)与RA-ILD组(n=189)，比较两组患者一般资料、临床特征、用药情况及实验室指标的差异。根据RA相关抗体指标的不同，采用LCA法将712例患者分为3个潜在类别：抗体指标高危组(n=364例)、抗体指标中危组(n=205例)及抗体指标低危组(n=143例)。采用单因素方差分析比较3组的临床特征，并计算RA-ILD的患病率；采用多因素logistic回归分析RA-ILD发生的独立影响因素。结果 单纯RA组与RA-ILD组在性别、年龄、吸烟史等方面差异有统计学意义(P<0.05)。抗体指标高、中、低危组在性别、年龄、醋酸泼尼松(PRED)及甲氨蝶呤(MTX)用药史、红细胞计数(RBC)、白细胞介素(IL)-2、IL-4、IL-10、IL-17、肿瘤坏死因子-α(TNF-α)、γ干扰素(INF-γ)、血清球蛋白、血清白蛋白水平方面差异有统计学意义(P<0.05)。其中，抗体指标高危组的男性占比、RBC、IL-2、IL-4、IL-10、IL-17、TNF-α、INF-γ、血清球蛋白水平等均高于抗体指标中、低危组，MTX用药比例低于抗体指标中危组，差异均有统计学意义(P<0.05或P<0.01)；抗体指标中危组的MTX用药比例高于抗体指标高危组及低危组，差异有统计学意义(P<0.05或P<0.01)；抗体指标低危组的女性占比、年龄等高于其他两组，差异有统计学意义(P<0.05或P<0.01)。3组RA-ILD的患病率分别为30.5%、23.9%、20.3%，差异有统计学意义(χ2=6.525，P=0.038)。多因素logistic回归分析结果显示，男性(OR=2.920，95%CI 1.722~4.952)、年龄(OR=1.055，95%CI 1.035~1.074)、IL-17(OR=1.013，95%CI 1.003~1.023)、TNF-α(OR=1.050，95%CI 1.017~1.083)、INF-γ(OR=0.962，95%CI 0.932~0.993)、血清白蛋白(OR=0.919，95%CI 0.869~0.971)、抗体指标高危(OR=1.725，95%CI 1.084~2.745)是RA患者并发ILD的独立影响因素。结论 RA患者抗体指标有明显的分类特征，抗体指标高危者RA-ILD患病率较高。男性、高龄、肝功能异常、细胞因子异常及抗体指标高危的患者更易发生RA-ILD，应及时制定并实施个体化干预措施，以提高患者的生存质量。

类风湿关节炎  /  潜在类别分析  /  间质性肺疾病

Objective To analyze the classification characteristics of rheumatoid arthritis (RA)-related antibodies and to investigate the factors influencing the development of RA-related interstitial pulmonary diseases (RA-ILD) in RA patients using latent class analysis (LCA). Methods A retrospective analysis of 712 RA patients treated at the Department of Rheumatology and Immunology of the Second Hospital of Shanxi Medical University from December 2019 to October 2022 was conducted. According to whether patients had RA-ILD or not, they were divided into simple RA group (n=523) and RA-ILD group (n=189). Then, the differences in general data, clinical features, medication use and laboratory indicators were compared between the two groups. Based on the differences in RA-related antibody indicators, 712 patients were divided into 3 latent categories using LCA: high-risk group (n=364), medium-risk group (n=205), and low-risk group (n=143).One-way analysis of variance was employed to compare clinical characteristics of the 3 groups, and the prevalence of RA-ILD was calculated. Multivariate logistic regression analysis was utilized to identify independent affect factors of RA-ILD. Results Significant differences in gender, age, and smoking history were observed between simple RA group and RA-ILD group (P<0.05). The high, medium and low risk groups exhibited significant differences in gender, age, prednisone (PRED) and methotrexate (MTX) medication history, Red blood cell count (RBC), interleukin-2 (IL-2), IL-4, IL-10, IL-17, TNF-α, interferon-γ (INF-γ), serum globulins, and white blood albumins (P<0.05). The high-risk group had a higher proportion of males, RBC, IL-2, IL-4, IL-10, IL-17, TNF-α, INF-γ, and serum globulin levels, and a lower proportion of MTX medication compared with medium- and low-risk groups (P<0.05 or P<0.01). The medium-risk group had a higher proportion of MTX administration than that in high- and low-risk groups (P<0.05 or P<0.01). The low-risk group had a higher proportion of females and older age than those in other two groups (P<0.05 or P<0.01). The prevalence of RA-ILD was 30.5%, 23.9% and 20.3% in the three groups, respectively. Multivariate logistic regression analysis indicated that male (OR=2.920, 95%CI 1.722-4.952), age (OR=1.055, 95%CI 1.035-1.074), IL-17 (OR=1.013, 95%CI 1.003-1.023), TNF-α (OR=1.050, 95%CI 1.017-1.083), INF-γ (OR=0.962, 95%CI 0.932-0.993), Serum albumin (OR=0.919, 95%CI 0.869-0.971) and high risk antibody indicators (OR=1.725, 95%CI 1.084-2.745) were independent predictors for RA-ILD. Conclusions RA patients exhibit distinct categories of antibody indicators, with a higher prevalence in high-risk patients with RA-ILD. RA-ILD is more likely to occur in male, elderly patients with abnormal liver function and high-risk antibody indictors. More attention should be paid to these patients and individualized interventions should be developed and implemented in a timely manner to improve the quality of patient survival.

rheumatoid arthritis  /  latent class analysis  /  interstitial pulmonary diseases
聂艳聪, 尹梅林, 王晓霞, 仇丽霞. 类风湿关节炎相关间质性肺疾病的影响因素分析：一项基于潜在类别分析的研究. 解放军医学杂志, 2025 , 50 (2) : 146 -153 . DOI: 10.11855/j.issn.0577-7402.1097.2024.1113
Yan-Cong Nie, Mei-Lin Yin, Xiao-Xia Wang, Li-Xia Qiu. Analysis of factors affecting rheumatoid-interstitial pulmonary diseases: a study based on an analysis of latent class[J]. Medical Journal of Chinese People’s Liberation Army, 2025 , 50 (2) : 146 -153 . DOI: 10.11855/j.issn.0577-7402.1097.2024.1113
正文
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类风湿关节炎(rheumatoid arthritis，RA)是以对称性多发性关节炎为特征的慢性全身性自身免疫性疾病[1-2]。肺部受累是最常见的关节外表现，间质性肺疾病(interstitial pulmonary diseases，ILD)是RA患者常见的一种弥漫性的肺实质疾病[3-4]。RA发展为类风湿关节炎相关间质性肺疾病(rheumatoid-interstitial pulmonary diseases，RA-ILD)的机制目前尚未明确，可能是由瓜氨酸化蛋白、抗瓜氨酸化蛋白抗体和免疫细胞引起的[5]。RA-ILD的病死率为13.9%，是RA患者的重要死因之一，死亡风险较单纯RA高2~10倍[6]。因此，RA-ILD的早期诊断、早期治疗尤为重要。
自身抗体可在RA患者表现典型的临床症状前产生，并具有一定的预测价值，在RA的早期诊断、治疗监测及预后评估中具有重要的应用价值。类风湿因子(rheumatoid factors，RF)是诊断RA的重要指标。但诊断RA还需要联合特异性较高的自身抗体，如抗环瓜氨酸多肽抗体(anti-cyclic citrulline polypeptide，抗CCP)、抗核周因子抗体(antiperinuclearfactor，APF)、抗角蛋白抗体(antikeratin antibody，AKA)等进行综合评估。由于抗体指标较多，临床工作中常难以做出整体评估。潜在类别分析(latent class analysis，LCA)作为一种将潜在变量理论与分类变量相结合的统计分析方法，可用于探索观察到的分类变量背后的潜变量特征。LCA能同时处理多个指标，并结合所有指标进行综合诊断。因此，本研究采用LCA对自身抗体进行整体评估后将RA患者分组，分析不同组别患者的一般资料、临床特征、用药情况、实验室指标及RA-ILD患病率的差异，进一步探讨RA-ILD发生的独立影响因素，旨在为患者的个性化干预提供指导。
1 资料与方法
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1.1 研究对象
收集2019年12月－2022年10月在山西医科大学第二医院风湿免疫科临床确诊的712例RA患者资料进行回顾性分析。纳入标准：(1)RA诊断符合1987年美国风湿病学会(American College of Rheumatology，ACR)修订的RA分类标准[7]或2010年ACR/欧洲抗风湿病联盟(European League Against Rheumatology，EULAR)修订的RA分类标准[8]；(2)出院诊断时RA为主要诊断；(3)入院期间行高分辨CT(HRCT)检查；(4)年龄≥18岁；(5)临床资料完整。排除标准：(1)合并肺部感染、支气管哮喘或慢性阻塞性肺疾病等其他肺病；(2)合并肺尘埃沉着病等理化因素所致的肺病；(3)合并慢性心功能不全、肝肾功能损害等；(4)合并其他类型结缔组织病；(5)合并血液病或肿瘤；(6)妊娠期或哺乳期女性。RA-ILD的诊断根据HRCT检查结果，并结合2018年ILD专家诊断共识[9]。根据RA-ILD诊断结果将所有患者分为单纯RA组(n=523例)与RA-ILD组(n=189)。本研究获山西医科大学第二医院伦理委员会审批[(2023)YX第(136)号]。
1.2 住院资料收集
通过医院信息系统(Hospital Information System，HIS)收集患者的一般资料、临床特征、用药情况、实验室检查结果。一般资料：性别、年龄、体重指数(body mass index，BMI)、病程、吸烟史、饮酒史、高血压史、糖尿病史。临床特征：晨僵时间、肿胀关节个数、疼痛关节个数。用药情况：醋酸泼尼松(prednisone，PRED)、甲氨蝶呤(methotrexate，MTX)、来氟米特(leflunomide，LEF)。实验室检查指标：(1)血常规，红细胞计数(red blood cell，RBC)、血红蛋白(hemoglobin，HB)、血小板计数(platelet，PLT)、白细胞计数(white blood cell，WBC)；(2)炎性标志物，红细胞沉降率(erythrocyte sedimentation rate，ESR)、C反应蛋白(C-reactive protein，CRP)；(3)细胞因子，白细胞介素(interleukin，IL)-2、IL-4、IL-6、IL-10、IL-17、肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)、γ干扰素(interferon-γ，INF-γ)；(4)肝功能，血清球蛋白、血清白蛋白、血清总蛋白。
1.3 自身抗体指标收集
RA相关自身抗体的实验室检测均使用患者的血清标本。本研究纳入的自身抗体指标：类风湿因子(rheumatoid factors，RF，包括RF-IgG、RF-IgA、RF-IgM)、抗核周因子(antiperinuclear factor，APF)、抗角蛋白抗体(anti-keratin antibody，AKA)、抗核抗体(antinuclear antibody，ANA)、抗环瓜氨酸多肽(anti-cyclic peptide containing citrulline，CCP)、抗聚丝蛋白抗体(anti-filaggrin antibody，AFA家族)、抗RA33抗体，共9个RA相关的指标。不同的指标采用不同的检测方法，其中RF采用免疫比浊法，APF、AKA、ANA采用间接免疫荧光法，CCP、AFA家族采用化学发光免疫分析方法，抗RA33抗体采用免疫印迹法。在进行LCA分析时自身抗体指标的赋值如表1所示。
1.4 LCA算法
潜在类别模型又称潜类模型(latent class model，LCM)，是根据个体在外显指标上的反应模式来进行参数估计，同时融入因子分析和结构方程模型的思想[10]。建立一个完整的LCM需要以下步骤：概率参数化、参数估计、模型识别、拟合优度评价、潜在分类与结果解释[11]。潜在类别分析类别数的判定通过Akaike信息准则(AIC)、Bayesian信息准则(BIC)、校正的BIC(aBIC)、Entropy指数、Lo-Mendell-Rubin检验(LMRT)和自助似然比检验(BLRT)进行判断。
模型适配检验方法主要有Pearson χ2、似然比χ2(G2)、AIC、BIC，这4个模型评价指标已经成为评价LCM拟合效果的标准。其中，AIC、BIC和aBIC这3项适配指标数值越小越好[12]；在LCA中还常采用Entropy指数来评估分类的精确程度，其取值范围为0~1[13]，当Entropy≈0.6时，表明约有20%的个体存在分类的错误，Entropy≈0.8时表明分类的准确率超过了90%[14]；显著性检验指标包括LMRT和BLRT，当LMRT和BLRT的P<0.05时，表示K类模型的拟合程度优于K-1类[15]。
1.5 统计学处理
采用Mplus 8.3统计软件进行LCA，采用SPSS 26.0软件进行统计分析。计量资料符合正态分布者以$\bar{x}±s$表示，两组间比较采用独立样本t检验，多组间比较采用单因素方差分析，进一步两两比较采用Bonferroni检验；非正态分布者以M(Q1，Q3)表示，组间比较采用秩和检验。计数资料以例(%)表示，组间比较采用χ2检验。采用多因素logistic回归分析RA患者发生ILD的独立影响因素，并使用比值比(odds ratio，OR)的95%置信区间(95% confidence interval，95%CI)来表示。P≤0.05为差异有统计学意义。
2 结果
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2.1 单纯RA组与RA-ILD组的基线特征比较
712例RA患者的年龄为(55.1±12.5)岁，男性210例(占29.5%)，女性502例(占70.5%)，男女比例为3:7，病程4.0(1.0，10.0)年。与单纯RA组比较，RA-ILD组男性占比较高、年龄较大、疼痛关节数较多、使用PRED的占比较高，WBC、ESR、CRP、IL-2、IL-4、IL-10、IL-17、TNF-α、INF-γ、APF阳性占比、AKA阳性占比及AFA家族阳性占比升高，血清总蛋白、血清白蛋白水平降低，差异有统计学意义(P≤0.05)，而两组间BMI、病程、高血压史、糖尿病史、晨僵时间、肿胀关节数、使用MTX的比例、使用LEF的比例、RBC、HG、PLT、IL-6、血清球蛋白、RF-IgA、RF-IgG、RF-IgM、ANA、CCP、抗RA33等比较差异均无统计学意义(P>0.05)(表2)。
2.2 基于自身抗体指标的LCA分析
本研究基于9个抗体指标进行LCA分析，对RA患者进行分类，共进行了7个类别模型的拟合，其中Class 1表示依据9个指标将研究对象分为1组，同理Class 2˗7表示将研究对象分为2~7组。LCA模型从Class 1到Class 7的拟合统计数据如表3所示。显著性检验指标LMRT、BLRT<0.05时，分类效果优于前一类别，据此排除Class 1、Class 5、Class 6、Class 7；拟合指数AIC、BIC、aBIC越低，拟合效果越好，因此锁定Class 3、Class 4；通过Entropy值来选择最优模型，Entropy值越大表明模型分类准确度越高，Class 3中Entropy值为0.825。综合考虑，将Class 3作为最佳模型，即通过9个抗体指标将研究对象分为3组。
2.3 潜在类别的命名
3组中RF-IgG、RF-IgA、RF-IgM、APF、AKA、ANA、抗CCP、AFA家族、抗RA33对应的概率分布如图1。组1占总体的51%，APF、AKA、ANA、抗CCP、AFA家族阳性发生的条件概率均>69%，可认为该组是APF、AKA、ANA、抗CCP、AFA家族指标阳性的倾向类，且整体指标阳性条件概率明显高于其他组别，故将组1命名为抗体指标高危组；组3占总体的20%，9个抗体指标阳性的条件概率均<0.26，故将组3命名为抗体指标低危组；组2占总体的29%，命名为抗体指标中危组。
2.4 3组间的基线特征比较
单因素方差分析显示，3组在性别、年龄、使用PRED的比例、使用MTX的比例、RBC、IL-2、IL-4、IL-10、IL-17、TNF-α、INF-γ、血清球蛋白、血清白蛋白方面差异有统计学意义(P<0.05)。其中，抗体指标高危组的男性占比、RBC、IL-2、IL-4、IL-10、IL-17、TNF-α、INF-γ、血清球蛋白水平等均高于抗体指标中、低危组，MTX用药比例低于抗体指标中危组，差异均有统计学意义(P<0.05或P<0.01)；抗体指标中危组的MTX用药比例高于抗体指标高危组及低危组，差异有统计学意义(P<0.05或P<0.01)；抗体指标低危组的女性占比、年龄等高于其他两组，差异有统计学意义(P<0.05或P<0.01)(表4)。
2.5 抗体指标低、中、高危组患者的患病情况比较
712例患者中RA-ILD的患病率为26.5%(189/712)，其中抗体指标高危组RA-ILD的患病率为30.5%(111/364)，中危组为23.9%(49/205)，低危组为20.3%(29/143)(表5)。按照α=0.05的检验水准，经Pearson χ2检验，3组RA-ILD的患病率差异有统计学意义(χ2=6.525，P=0.038)；按照α=0.017的检验水准，经Bonferroni检验进行两两比较，3组间差异也均有统计学意义。
2.6 多因素logistic回归分析结果
将上述20个有临床意义的变量(男性、年龄、吸烟史、饮酒史、疼痛关节数、PRED、WBC、ESR、CRP、IL-2、IL-4、IL-10、IL-17、TNF-α、INF-γ、血清总蛋白、血清白蛋白、APF、AKA、AFA家族)及抗体指标高、中、低危作为自变量，是否合并RA-ILD作为因变量，采用多因素logistic回归分析RA患者并发ILD的影响因素。结果显示，男性(OR=2.920，95%CI 1.722~4.952)、年龄(OR=1.055，95%CI 1.035~1.074)、IL-17(OR=1.013，95%CI 1.003~1.023)、TNF-α(OR=1.050，95%CI 1.017~1.083)、抗体指标高危(OR=1.725，95%CI 1.084~2.745)为RA并发ILD的独立危险因素，INF-γ(OR=0.962，95%CI 0.932~0.993)、血清白蛋白(OR=0.919，95%CI 0.869~0.971)为RA并发ILD的保护因素，差异均有统计学意义(P<0.05)(表6)。
3 讨论
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探索性LCA一般不设定潜在类别数目和特定的参数条件，从潜在类别数为1的模型开始，逐步增加类别数，并进行模型的拟合优度检验，根据模型拟合优度值选择最佳模型[11]。其纳入的变量为分类变量，同时提高了分类变量的分析价值，可更加深入了解分类变量的潜在影响因素。
关于RA-ILD的研究一直是风湿疾病领域的热点，本研究基于RA患者抗体指标将其分为高、中、低危3组，比较不同组别RA患者的临床特征和RA-ILD患病情况，并通过多因素logistic回归分析RA并发ILD的独立影响因素。3个潜在类别组在临床特征、实验室检查及RA-ILD发生情况等方面存在差异，证实该分类具有临床意义，为临床治疗提供了新的视角，也为个性化管理提供了理论支持[16]。
抗体指标高危组男性患者较多，伴有RBC、IL-2、IL-4、IL-10、IL-17、TNF-α、INF-γ、血清球蛋白水平等实验室检查结果异常。针对该类人群，建议男性患者定期到医院检查，建议血常规、ESR、CRP等指标每半个月复查一次，RA相关抗体每年复查一次；如果检查中发现存在肝损伤，则需要在医师指导下寻找具体病因以给予针对性处理。相较于其他两组，抗体指标中危组特异性并不明显，主要表现在MTX用药比例较高。此类患者应定期复诊，寻求积极药物治疗，目前常用的包括免疫抑制剂治疗、生物制剂治疗、激素治疗、中医治疗、抗肺纤维化治疗等[17]。抗体指标低危组多女性患者，且年龄略大。更年期是女性RA的高发年龄段，建议中老年女性患者在生活中注意休息，避免身体过度劳累和精神刺激；注意保暖；进食高蛋白、高热量、易消化的食物，少吃辛辣刺激性食物及生冷、油腻食品；适度进行锻炼，提高身体免疫力；发现异常时应尽早就医，早发现、早诊断、早治疗，以免贻误病情。
抗体指标高危组RA-ILD的患病率明显高于抗体指标中、低危组(30.5% vs. 23.9% vs. 20.3%)。本研究纳入人群中，RA-ILD的总体患病率达26.5%，与既往流行病学调查显示的RA-ILD患病率(3%~80%)[18]相符，提示临床医师要加强对RA患者的管理，通过合理的药物治疗控制关节炎，至少应降低RA的疾病活动度，从而预防RA患者新发或进展为肺间质纤维化；患者应完善胸部HRCT、肺功能检查等，有助于早期发现肺间质病变并及早治疗；建议患者调整不良的生活方式，如尽早戒烟、合理饮食、控制体重等；定期复查，若有任何不适及时到医院随访[19]。
本研究发现，男性是RA患者并发ILD的独立危险因素，男性RA患者发生ILD的风险是女性的2.920倍。Solomon等[20]关于RA合并肺间质病变危险因素的研究同样发现男性为RA-ILD的危险因素。另有文献报道，年龄每增加1岁可使RA患者发生ILD的风险增加6.6%[21]，是RA-ILD的高危特征指标。本研究结果显示，年龄与RA-ILD的发生呈正相关，且年龄每增加1岁，RA患者发生ILD的风险就增加5.5%。生物学标志物在RA-ILD的诊断中可发挥重要作用，已有研究证实，RF、抗CCP、ACPA(抗瓜氨酸蛋白抗体谱)及抗核抗体谱的部分抗体为RA-ILD的危险因素[22]。本研究结果证实了生物标志物IL-17、TNF-α、INF-γ、血清白蛋白均与RA-ILD的发生相关。同时，本研究还发现，抗体指标高危可作为RA-ILD的独立影响因素，提示利用抗体指标将RA患者进行分类对于探究RA-ILD的发生具有重要的指导意义，但目前尚未发现抗体指标中、低危与RA-ILD有关联，因此需要后续进一步探索。
本研究存在以下不足：采用的是回顾性研究方法，仅收集了单中心的RA患者的临床数据，纳入的特征为一些客观性指标，并未收集患者的主观评价指标。未来可进行多中心队列研究，同时增加外部验证，以提高本模型对RA患者的分类能力。
综上，本研究引入LCA算法，根据RA自身抗体指标将人群分为抗体指标高、中、低危组，3组在一般情况、临床特征、实验室指标及RA-ILD患病率方面存在明显差异；进一步分析RA-ILD的独立影响因素发现，这种分组是导致RA患者并发ILD的独立危险因素，对识别RA-ILD的高危患者具有重要意义，有助于研究人员和临床医师针对不同的患者人群设计临床试验和医疗保健计划。
文献
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doi: 10.11855/j.issn.0577-7402.1097.2024.1113
  • 接收时间：2023-08-18
  • 首发时间：2025-11-10
  • 出版时间：2025-02-28
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  • 收稿日期：2023-08-18
  • 录用日期：2023-11-08
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    1山西医科大学公共卫生学院，山西太原 030000
    2山西医科大学第二临床医学院，山西太原 030000
    3山西医科大学第二医院风湿免疫科，山西太原 030000

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王晓霞，E-mail：
仇丽霞，E-mail：
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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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