Abstract
目的
分析类风湿因子(rheumatoid factor,RF)或抗环瓜氨酸化多肽(cyclic-citrullinated peptide,CCP)抗体阳性银屑病关节炎(psoriatic arthritis,PsA)患者的临床和实验室检查特点。
方法
共纳入2007年1月至2019年6月于北京大学第三医院风湿免疫科住院的PsA患者77例,所有患者均符合2006年美国风湿病学会修订的《银屑病关节炎的分类诊断标准》或《Moll和Wright标准》,并进行了RF及抗CCP抗体检测,根据血清中是否检测到抗CCP抗体或RF将所有患者分为抗CCP抗体或RF阳性组15例、抗CCP抗体或RF阴性组62例;根据血清中是否检测到抗CCP抗体将所有患者分为抗CCP抗体阳性组7例、抗CCP抗体阴性组70例,收集患者的临床及实验室资料,比较RF或抗CCP抗体阳性和阴性PsA患者的临床及实验室指标的差异,并单独比较了抗CCP抗体阳性和阴性PsA患者的临床及实验室指标的差异。
结果
在77例患者中,RF或抗CCP抗体阳性者15例,其中仅RF阳性者8例,仅抗CCP抗体阳性者2例,两者均为阳性者5例。RF或抗CCP抗体阳性组PsA患者年龄较阴性组大[(58.2±14.8)岁 vs.(46.69±12.27)岁,P=0.002],更易出现掌指关节、肘关节、肩关节受累。抗CCP抗体阳性组PsA患者较阴性组年龄大[(62.43±14.34)岁vs.(47.59±12.75)岁,P=0.005],RF阳性率高,血纤维蛋白原水平高。抗CCP抗体阳性组PsA患者均为多关节炎,阴性组患者中有68.6%的患者为多关节炎,但两组间差异无统计学意义。RF或抗CCP抗体阳性和阴性以及抗CCP抗体阳性和阴性组PsA患者在腊肠指/趾表现、关节骨质破坏、指/趾甲改变、附着点炎方面差异无统计学意义。
结论
部分PsA患者血清中可检测到RF或抗CCP抗体;RF或抗CCP抗体阳性PsA患者更易出现掌指关节、肘关节、肩关节受累,年龄更大;抗CCP抗体阳性PsA患者年龄更大,RF阳性率、纤维蛋白原水平高。
Keywords: 银屑病关节炎, 类风湿因子, 抗环瓜氨酸化多肽抗体
Abstract
Objective
To analyze the clinical and laboratory features of psoriatic arthritis (PsA) patients with positive rheumatoid factor(RF)or anti-cyclic citrullinated peptide(CCP)antibody.
Methods
In the study, 77 PsA patients who were hospitalized in the Department of Rheumatology and Immunology of Peking University Third Hospital from January 2007 to June 2019 were enrolled. All the patients met Classification Criteria for Psoriatic Arthritis or Moll or Wright Criteria. Rheumatoid factor (RF) and anti-cyclic-citrullinated peptide (CCP) antibody were tested in these patients. According to whether anti-CCP antibody or RF was detected in serum, all the patients were divided into anti-CCP antibody or RF positive group (15 cases), anti-CCP antibody or RF negative group (62 cases). According to the detection of anti-CCP antibody in serum, all the patients were divided into anti-CCP antibody positive group (7 cases) and anti-CCP antibody negative group (70 cases). Clinical and laboratory data were collected. The differences of clinical and laboratory indicators between the RF or anti-CCP antibody positive and negative PsA patients were compared. Clinical and laboratory indicators between the anti-CCP antibody positive and negative patients were also compared.
Results
Among the 77 patients, 15 were RF or anti-CCP antibody positive, of whom 8 were only RF positive and 2 were only anti-CCP antibody positive, and both of RF and anti-CCP antibody were positive in 5 cases. The RF or anti-CCP antibody positive PsA patients were older than those in the negative group [(58.2±14.8) years vs.(46.69±12.27)years, P=0.002]. And metacarpophalangeal joints, elbow joints and shoulder joints were more likely to be involved in RF or anti-CCP antibody positive PsA patients. PsA patients in the anti-CCP antibody positive group were older than those in the negative group [(62.43±14.34) years vs.(47.59±12.75)years old, P=0.005]. The positive rate of RF and serum level of fibrinogen in the anti-CCP antibody positive group were higher than those in the negative group. The PsA patients in the anti-CCP antibody positive group were all polyarthritis, while 68.6% patients in the negative group were polyarthritis, but there was no statistical difference between the two groups. There was no statistical difference in sausage fingers/toes, changes in nails and enthesitis, and bone erosion on radiographs between the RF or anti-CCP antibody positive and negative PsA patients. There was also no statistical difference in sausage fingers/toes,bone erosion on radiographs,and changes in nails and enthesitis between the anti-CCP antibody positive and negative patients.
Conclusion
RF and anti-CCP antibodies can be detected in the serum of some PsA patients. RF or anti-CCP antibody positive PsA patients were older than those in negative PsA patients. Metacarpophalangeal joints, elbow joints and shoulder joints were more likely to be involved in RF or anti-CCP antibody positive PsA patients. Anti-CCP antibody positive PsA patients were older and had higher levels of RF positive rate and fibrinogen level.
Keywords: Psoriatic arthritis, Rheumatoid factor, Anti-cyclic citrullinated peptide antibody
类风湿因子(rheumatoid factor,RF)和抗环瓜氨酸化多肽(anti-citrullinated peptide antibody, CCP)抗体是类风湿关节炎(rheumatoid arthritis, RA)的特异性抗体,对RA的诊断及鉴别诊断有重要意义。近年来,有研究发现部分银屑病关节炎(psoriatic arthritis,PsA)患者血清中也可检测到RF或抗CCP抗体[1,2,3],且有文献报道抗CCP抗体阳性PsA患者在临床表现及实验室检查特点方面较阴性患者有所不同[4,5],但各文献报道不一,目前尚缺乏定论。对于抗CCP抗体阳性PsA患者究竟应诊断为PsA还是银屑病合并RA也尚存争议。本研究通过回顾性分析PsA患者的临床及实验室资料,探讨PsA患者血清RF或抗CCP抗体阳性率,及RF或抗CCP抗体阳性与临床及实验室特点的关系。
1. 资料与方法
1.1. 研究对象
本研究纳入2007年1月至2019年6月于北京大学第三医院风湿免疫科住院的PsA患者77例,所有患者诊断均符合2006年美国风湿病学会修订的《银屑病关节炎的分类诊断标准》[6]或《Moll和Wright标准》[7]。根据血清中是否检测到RF或抗CCP抗体将PsA患者分为RF或抗CCP抗体阳性组15例和阴性组62例,根据是否存在抗CCP抗体分为抗CCP抗体阳性组7例和抗CCP抗体阴性组70例。
1.2. 研究方法
收集77例患者的基本信息、临床特点、实验室及影像学检查结果、治疗情况等资料并进行回顾性分析。临床信息包括银屑病病程、关节炎病程、吸烟及饮酒史、受累关节、腊肠指/趾、指/趾甲改变、附着点炎、其他伴随疾病情况等;实验室检查结果包括RF、抗CCP抗体、红细胞沉降率、C反应蛋白、免疫球蛋白、血常规、生化、凝血等;影像学检查主要为是否有关节骨质破坏等。
1.3. 统计学分析
应用SPSS 24.0软件进行统计学分析,其中计数资料以例数及百分数表示,组间比较采用Pearson卡方、连续性校正卡方检验或连续性Fisher’s精确检验,计量资料以均数±标准差或中位数(最小值,最大值)表示,组间比较时,正态分布数据采用t检验,非正态分布数据采用非参数检验,P<0.05为差异有统计学意义。
2. 结果
2.1. RF或抗CCP抗体阳性患者基本情况的比较
本研究共纳入患者77例,其中男性44例,RF或抗CCP抗体阳性患者共15例,其中仅有RF阳性患者8例,2例患者仅有抗CCP抗体阳性,两者均为阳性者5例。总体平均年龄为(48.94±13.41)岁,阳性组平均年龄为(58.2±14.8)岁,阴性组平均年龄为(46.69±12.27)岁,两组间差异有统计学意义(P=0.002)。阳性组与阴性组患者在银屑病病程及关节炎病程上差异无统计学意义(表1)。
1.
RF或抗CCP抗体阳性及阴性PsA患者基本情况的比较
Comparison of general conditions of RF or anti-CCP antibody positive and negative PsA patients
| Items | Positive group(n=15) | Negative group(n=62) | P |
| *Pearson Chi-square test. | |||
| Male,n(%) | 9(60.0) | 35(56.45) | 0.803* |
| Age /years, x±s | 58.2±14.8 | 46.69±12.27 | 0.002 |
| The course of psoriasis/years, x±s | 15.04±12.57 | 13.79±12.41 | 0.727 |
| The course of arthritis/years, (Min, Max) | 2(0.08,18.00) | 1(0.02,20.00) | 0.517 |
2.2. RF或抗CCP抗体阳性及阴性患者临床特点和实验室指标的比较
RF或抗CCP抗体阳性组患者中,60.0%出现肩关节受累,46.7%的患者肘关节受累,73.3%的患者掌指关节受累。阴性组患者中,分别有25.8%、17.7%、38.7%的患者出现肩关节、肘关节、掌指关节受累,阳性组患者较阴性组更易出现肩关节、肘关节、掌指关节受累,差异有统计学意义。两组患者在腕关节、近端指间关节、远端指间关节、髋关节、膝关节、踝关节、跖趾关节、近端趾间关节、远端趾间关节、脊柱、骶髂关节受累、腊肠指/趾表现、指/趾甲改变、附着点炎、银屑病皮疹上差异无统计学意义(表2)。阳性组表现为对称性关节炎及多关节炎的患者比例较阴性组更高,但差异无统计学意义(表2)。
2.
RF或抗CCP抗体阳性及阴性PsA患者临床特点的比较
Comparison of clinical characteristics of RF or anti-CCP antibody positive and negative PsA patients
| Items | Positive group(n=15) | Negative group(n=62) | P |
| MCP, metacarpophalangeal; PIP, proximal interphalangeal; DIP, distal interphalangeal; MTP, metatarsophalangeal; 14 articular regions, bilateral elbow, wrist, metacarpophalangeal, proximal interphalangeal, knee, ankle and metatarsophalangeal joints;*Pearson Chi-square test, # Continuity correction Chi-square test, ▲Fisher’s exact test. | |||
| Shoulder joint involvement, n(%) | 9(60.0) | 16(25.8) | 0.026# |
| Elbow joint involvement, n(%) | 7(46.7) | 11(17.7) | 0.042# |
| Wrist joint involvement, n(%) | 10(66.7) | 26(41.9) | 0.085* |
| MCP joint involvement, n(%) | 11(73.3) | 24(38.7) | 0.016* |
| PIP joint involvement, n(%) | 12(80.0) | 33(53.2) | 0.059* |
| DIP joint involvement, n(%) | 6(40.0) | 22(35.5) | 0.744* |
| Hip joint involvement, n(%) | 2(13.3) | 7(11.3) | 1.000# |
| Knee joint involvement, n(%) | 11(73.3) | 36(58.1) | 0.277* |
| Ankle joint involvement, n(%) | 6(40.0) | 20(32.3) | 0.569* |
| MTP joint involvement, n(%) | 8(53.3) | 23(37.1) | 0.250* |
| PIP joint involvement of foot, n(%) | 1(6.7) | 15(24.2) | 0.252# |
| DIP joint involvement of foot, n(%) | 0(0.0) | 9(14.5) | 0.262# |
| Spinal involvement, n(%) | 2(13.3) | 7(11.3) | 1.000# |
| Sacroiliac joint involvement, n(%) | 2(13.3) | 12(19.4) | 0.865# |
| More than 3 articular regions involvement (14 articular regions), n(%) | 13(86.7) | 42(67.7) | 0.255# |
| Wrist, MCP or PIP (hand) joint involvement, n(%) | 14(93.3) | 47(75.8) | 0.252# |
| Symmetrical arthritis, n(%) | 12(80.0) | 34(54.8) | 0.075* |
| Oligoarthritis (4 or less joints involved) , n(%) | 2(13.3) | 17(27.4) | 0.423# |
| Sausage fingers/toes, n(%) | 5(33.3) | 18(30.5)(n=59) | 1.000# |
| Changes in nails, n(%) | 6(50.0)(n=12) | 12(27.9)(n=43) | 0.274# |
| Enthesitis, n(%) | 2(16.7)(n=12) | 15(34.9)(n=43) | 0.393# |
| Psoriasis rash, n(%) | 12(100.0)(n=12) | 39(90.7)(n=43) | 0.566▲ |
RF或抗CCP抗体阳性组及阴性组患者的红细胞沉降率、C反应蛋白、免疫球蛋白、纤维蛋白原、D-二聚体等实验室指标之间差异无统计学意义,两组患者关节骨质破坏的发生率差异无统计学意义(表3)。
3.
RF或抗CCP抗体阳性及阴性PsA患者实验室及影像学检查的比较
Comparison of laboratory and imaging examinations in RF or anti-CCP antibody positive and negative PsA patients
| Items | Seropositive group(n=15) | Seronegative group(n=62) | P |
| ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; IgG, immunoglobulin G; IgA, immunoglobulin A; IgM, immunoglobulin M;# Continuity correction Chi-square test. | |||
| ESR/(mm/h), x±s | 55.15±30.89(n=13) | 39.09±30.51(n=55) | 0.067 |
| CRP/(mg/L), x±s | 46.95(2.10, 173.00)(n=14) | 24.70(1.00, 551.00)(n=59) | 0.245 |
| IgG/(g/L), x±s | 15.97±4.44(n=12) | 13.47±3.02(n=45) | 0.054 |
| IgA/(g/L), x±s | 3.25±1.52(n=12) | 3.23±1.28(n=46) | 0.963 |
| IgM/(g/L), x±s | 1.35±1.05(n=11) | 1.15±0.53(n=45) | 0.789 |
| Fibrinogen/(g/L), x±s | 4.97±1.51(n=12) | 4.38±1.38(n=44) | 0.231 |
| D-dimer/(mg/L), M(Min, Max) | 0.78(0.11, 2.86)(n=12) | 0.31(0, 2.76)(n=42) | 0.121 |
| Bone erosion on radiograph,n(%) | 4(33.3)(n=12) | 19(35.8)(n=53) | 1.000# |
2.3. 抗CCP抗体阳性及阴性患者的比较
在77例患者中,有7例患者血清抗CCP抗体阳性。抗CCP抗体阳性组患者年龄为(62.43±14.34)岁,阴性组患者年龄为(47.59±12.75)岁,两组间差异有统计学意义,阳性组患者年龄较大。两组患者从皮疹发生至发展为关节炎时间、银屑病及关节炎病程差异无统计学意义(表4)。
4.
抗CCP抗体阳性及阴性PsA患者一般情况的比较
Comparison of the general conditions of anti-CCP antibody positive and negative PsA patients
| Items | Anti-CCP antibody positive group (n=7) |
Anti-CCP antibody negative group (n=70) |
P |
| # Continuity correction Chi-square test. | |||
| Male,n(%) | 5(71.4) | 39(55.7) | 0.689# |
| Age /years, x±s | 62.43±14.34 | 47.59±12.75 | 0.005 |
| The course of psoriasis/years, x±s | 13.14±6.20 | 14.13±12.85 | 0.873 |
| The course of arthritis/years, M(Min, Max) | 2(0.83, 18) | 1(0.02, 20) | 0.871 |
| Duration between skin onset and arthritis onset/years, M(Min, Max) | 7.9(-1, 20)(n=7) | 9.3(-2, 45)(n=64) | 0.825 |
本研究中,抗CCP抗体阳性组患者表现为多关节炎、对称性关节炎、手关节炎比例较阴性组高,但两组间差异无统计学意义,且各关节受累、腊肠指/趾表现、指/趾甲改变、附着点炎、银屑病皮疹上差异无统计学意义(表5)。
5.
抗CCP抗体阳性及阴性PsA患者临床特点的比较
Comparison of clinical characteristics of anti-CCP antibody positive and negative PsA patients
| Items | Anti-CCP antibody positive group(n=7) |
Anti-CCP antibody negative group(n=70) |
P |
| MCP, metacarpophalangeal; PIP, proximal interphalangeal; DIP, distal interphalangeal; MTP, metatarsophalangeal; 14 articular regions, bilateral elbow, wrist, metacarpophalangeal, proximal interphalangeal, knee, ankle and metatarsophalangeal joints;#Continuity correction Chi-square test, ▲Fisher’s exact test. | |||
| Shoulder joint involvement, n(%) | 5(71.4) | 20(28.6) | 0.059# |
| Elbow joint involvement, n(%) | 4(57.1) | 14(20.0) | 0.081# |
| Wrist joint involvement, n(%) | 6(85.7) | 30(42.9) | 0.077# |
| MCP joint involvement, n(%) | 6(85.7) | 29(41.4) | 0.065# |
| PIP joint involvement, n(%) | 7(100.0) | 38(54.3) | 0.053# |
| DIP joint involvement, n(%) | 3(42.9) | 25(35.7) | 1.000# |
| Hip joint involvement, n(%) | 1(14.3) | 8(11.4) | 1.000▲ |
| Knee joint involvement, n(%) | 5(71.4) | 42(60.0) | 0.853# |
| Ankle joint involvement, n(%) | 2(28.6) | 24(34.3) | 1.000# |
| MTP joint involvement, n(%) | 3(42.9) | 28(40.0) | 1.000# |
| PIP joint involvement of foot, n(%) | 1(14.3) | 15(21.4) | 1.000# |
| DIP joint involvement of foot, n(%) | 0(0) | 9(12.9) | 0.590▲ |
| Spinal involvement, n(%) | 1(14.3) | 8(11.4) | 1.000▲ |
| Sacroiliac joint involvement, n(%) | 0(0) | 14(20.0) | 0.427# |
| More than 3 articular regions involvement(14 articular regions), n(%) | 7(100.0) | 48(68.6) | 0.188# |
| Wrist, MCP or PIP(hand) joint involvement, n(%) | 7(100.0) | 54(77.1) | 0.351# |
| Symmetrical arthritis , n(%) | 6(85.7) | 40(57.1) | 0.287# |
| Oligoarthritis (4 or less joints involved), n(%) | 0(0) | 19(27.1) | 0.259# |
| Sausage fingers/toes, n(%) | 2(28.6)(n=7) | 21(31.3)(n=67) | 1.000# |
| Changes in nails, n(%) | 2(50.0) (n=4) | 16(31.4)(n=51) | 0.833# |
| Enthesitis, n(%) | 0(0) (n=4) | 17(33.3)(n=51) | 0.408# |
| Psoriasis rash, n(%) | 4(100.0)(n=4) | 47(92.2)(n=51) | 1.000▲ |
抗CCP抗体阳性组中RF阳性率为71.4%,抗CCP抗体阴性组患者中RF阳性率为11.4%(P<0.001)。抗CCP抗体阳性组患者纤维蛋白原水平明显高于阴性组,差异有统计学意义。两组间红细胞沉降率、C反应蛋白、免疫球蛋白、D-二聚体水平、关节骨质破坏方面差异无统计学意义(表6)。
6.
抗CCP抗体阳性及阴性PsA患者实验室及影像学检查的比较
Comparison of laboratory and imaging examinations of anti-CCP antibody positive and negative PsA patients
| Items | Anti-CCP antibody positive group(n=7) | Anti-CCP antibody negative group(n=70) | P |
| RF, rheumatoid arthritis; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; IgG, immunoglobulin G; IgA, immunoglobulin A; IgM, immunoglobulin M;# Continuity correction Chi-square test. | |||
| RF positive, n(%) | 5(71.4) | 8(11.4) | <0.001# |
| ESR/(mm/h), x±s | 58.33±40.02(n=6) | 40.60±29.95(n=62) | 0.283 |
| CRP/(mg/L), M(Min, Max) | 69.2(2.1, 173.0)(n=7) | 23.9(1.0, 551.0)(n=66) | 0.459 |
| IgG/(g/L), x±s | 13.90±4.10(n=5) | 14.01±3.46(n=52) | 0.902 |
| IgA/(g/L), x±s | 3.57±2.02(n=5) | 3.20±1.26(n=53) | 0.687 |
| IgM/(g/L), x±s | 1.50±1.58(n=5) | 1.16±0.52(n=51) | 0.635 |
| Fibrinogen/(g/L), x±s | 5.87±1.30(n=4) | 4.40±1.38(n=52) | 0.048 |
| D-dimer(mg/L), M(Min, Max) | 0.92(0.59, 2.86)(n=4) | 0.31(0, 2.76)(n=50) | 0.071 |
| Bone erosion on radiograph, n(%) | 3(42.9)(n=7) | 20(34.5)(n=58) | 0.985# |
3. 讨论
RF和抗CCP抗体对于RA的诊断具有重要意义,为2010年美国风湿病学会和欧洲抗风湿病联盟制定的《类风湿关节炎分类标准》的血清学指标[8],并被纳入早期RA分类标准[9]。2006年美国风湿病学会修订的《银屑病关节炎的分类诊断标准》将RF阴性列为PsA分类标准之一[6],近年来,有研究报道在部分PsA患者血清中也可检测到RF或抗CCP抗体,有文章报道RF阳性率为12.8%[10],抗CCP抗体阳性率为5.0%~20.6%[1,11]。在正常人群中,RF阳性率为5%,抗CCP抗体阳性率为1.4%[12]。本研究中RF阳性率为16.88%,抗CCP抗体阳性率为9.09%,与已知文献报道数据基本相符,可见RF及抗CCP抗体并非RA特有,不能仅依据RF或抗CCP抗体阳性区分RA及PsA,需结合患者临床及辅助检查特点进行综合判断。
关于RF或抗CCP抗体阳性与PsA临床表现及实验室指标之间的关联目前尚无定论,本研究中RF或抗CCP抗体阳性组患者较阴性组更易出现肩关节、肘关节、掌指关节受累,RF或抗CCP抗体阳性组多表现为对称性关节炎及多关节炎。
近年来的研究表明,抗CCP抗体阳性PsA患者在临床表现上与阴性患者有所差异,大多数文献表明抗CCP抗体阳性患者更多表现为对称性多关节炎,占70%以上[2,12],也有少数文献报道为50%~60%[1]。本研究中,抗CCP抗体阳性组患者均表现为多关节炎,表现为对称性关节炎患者比例均较阴性组高,但两组间差异无统计学意义。此外,抗CCP抗体阳性组患者手关节炎发生比例较阴性组高。本研究数据与大部分文献报道一致,提示抗CCP抗体阳性PsA患者大多表现为对称性多关节炎,阳性组患者从皮疹发生至发展为关节炎时间相对较短,提示抗CCP抗体可能与银屑病患者发生关节炎相关。
在实验室数据方面,大部分文献报道抗CCP抗体阳性PsA患者血清中RF水平较阴性者高[4],但也有研究认为二者间缺乏显著关联[12],本研究中抗CCP抗体阳性组患者血清RF阳性率显著高于阴性组患者。此外,抗CCP抗体阳性组血清纤维蛋白原水平也明显升高,提示阳性组患者可能存在更加严重的炎症反应。
有研究认为抗CCP抗体阳性患者更易发生侵蚀性关节炎[1,5]。本研究中,抗CCP抗体阳性组关节骨质破坏发生率较阴性组高,但两组患者间差异无统计学意义,尚需更大样本量的研究进一步阐明。
PsA本身缺乏特异性血清学标志物[13],在部分PsA患者血清中也可检测到抗CCP抗体[14],此为诊断RA的特异性抗体,这就为抗CCP抗体阳性PsA患者的正确诊断带来了困难,关于此部分患者应诊断为PsA还是银屑病合并RA目前尚存在争议,本研究中RF或抗CCP抗体阳性的PsA患者皆符合PsA分类标准,且均经有经验的临床医生进行诊断。有研究认为可将抗CCP抗体水平作为鉴别诊断依据[1],综合临床表现和影像学特征进行综合判断。本研究中7例抗CCP抗体阳性的患者均表现为多关节炎及手关节受累,有6(85.7%)例为对称性关节炎,提示抗CCP抗体阳性的PsA患者具有RA的关节受累特点,可能需要考虑银屑病合并RA,而针对不同的诊断结果可能会选用不同的改善病情的抗风湿药进行治疗[15],目前尚需对抗CCP抗体在RA及PsA发病机制中所发挥的作用进行更深入的研究,并进一步寻找PsA相对特异的血清学标志物,以更好地进行疾病的诊断和治疗。
综上所述,在部分PsA患者血清中可检测到RF或抗CCP 抗体,此部分患者在临床表现、实验室指标方面与阴性患者有一定差异,尚需进一步更深入的研究来阐明上述结论,为PsA的精准诊断、分型以及治疗提供依据。
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