北京大学学报(医学版) ›› 2023, Vol. 55 ›› Issue (4): 631-635. doi: 10.19723/j.issn.1671-167X.2023.04.010

• 论著 • 上一篇    下一篇

血清IgA型抗鼠科肉瘤病毒癌基因同源物B1抗体在类风湿关节炎中的意义

金银姬,孙琳,赵金霞*(),刘湘源   

  1. 北京大学第三医院风湿免疫科, 北京 100191
  • 收稿日期:2020-07-31 出版日期:2023-08-18 发布日期:2023-08-03
  • 通讯作者: 赵金霞 E-mail:zhao-jinxia@163.com
  • 基金资助:
    国家自然科学基金(81273293);北京大学第三医院种子基金(Y87473-01)

Significance of IgA isotype of anti-v-raf murine sarcoma viral oncogene homologue B1 antibody in rheumatoid arthritis

Yin-ji JIN,Lin SUN,Jin-xia ZHAO*(),Xiang-yuan LIU   

  1. Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing 100191, China
  • Received:2020-07-31 Online:2023-08-18 Published:2023-08-03
  • Contact: Jin-xia ZHAO E-mail:zhao-jinxia@163.com
  • Supported by:
    the National Natural Science Foundation of China(81273293);the Seed Foundation of Peking University Third hospital(Y87473-01)

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摘要:

目的: 检测类风湿关节炎(rheumatoid arthritis,RA)患者血清中IgA型抗鼠科肉瘤病毒癌基因同源物B1(v-raf murine sarcoma viral oncogene homologue B1,BRAF)抗体水平,探讨IgA型抗BRAF抗体在RA血清中的表达及其与临床指标的相关性。方法: 纳入RA患者61例、干燥综合征(Sjögren’s syndrome,SS)患者16例、系统性红斑狼疮(systemic lupus erythematosus,SLE)患者16例、痛风患者16例、骨关节炎(osteoarthritis,OA)患者21例、健康对照22例,以重组的BRAF蛋白为抗原,应用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)方法检测所有患者血清中IgA型抗BRAF抗体水平,分析IgA型抗BRAF抗体与RA患者的临床和实验室指标的关系。采用SPSS 19.0进行统计学分析。结果: RA组患者血清中IgA型抗BRAF抗体滴度明显高于SLE组(P=0.011)、痛风组(P < 0.001)、OA组(P < 0.001)和健康对照组(P < 0.001)。RA组与SS组相比,IgA型抗BRAF抗体水平差异无统计学意义(P=0.762)。在类风湿因子、抗环瓜氨酸多肽(cyclic citrullinated peptide,CCP)抗体、抗角蛋白抗体阴性的RA患者中仍可以检测到IgA型抗BRAF抗体。RA患者血清中IgA型抗BRAF抗体水平与临床及实验室指标无相关性。将RA患者分为IgA型抗BRAF抗体升高组及正常组进行比较,结果显示两组在临床及实验室指标上差异均无统计学意义。结论: RA患者血清中IgA型抗BRAF抗体水平显著高于SLE、痛风、OA及健康对照组,且可在类风湿因子、抗CCP抗体及抗角蛋白抗体阴性的RA患者中升高,提示IgA型抗BRAF抗体可能参与RA的发病过程,且可能有助于血清阴性RA患者的诊断。

关键词: 类风湿关节炎, 鼠科肉瘤病毒癌基因同源物B1, IgA型抗BRAF抗体

Abstract:

Objective: To detect serum IgA isotype of anti-v-raf murine sarcoma viral oncogene homologue B1 (BRAF) antibody levels in the rheumatoid arthritis (RA) patients in order to investigate their clinical significance in RA. Methods: Serum samples were obtained from 61 RA patients, 21 osteoarthritis (OA) patients, 16 systemic lupus erythematosus (SLE) patients, 16 gout patients, 16 Sjögren's syndrome (SS) patients and 22 healthy controls. IgA isotype of anti-BRAF antibody levels in the sera were examined by enzyme-linked immunosorbent assay (ELISA). The associations between IgA isotype of anti-BRAF antibody levels and the clinical features including age, disease duration and laboratory parameters including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), disease activity score in 28 joints (DAS28), anti-cyclic citrullinated peptide (anti-CCP) antibody, immunoglobulin and BRAF protein levels in the RA patients were evaluated. Data analyses were performed by using SPSS 19.0 program. Results: The serum IgA isotype of anti-BRAF antibody levels in the RA patients were significantly higher than in the SLE, gout, OA patients and healthy controls, the P value was 0.011, < 0.001, < 0.001 and < 0.001, respectively. The serum IgA isotype of anti-BRAF antibody levels in the SS patients were also significantly higher than in the SLE, gout, OA patients and healthy controls, the P value was 0.029, 0.004, 0.001 and < 0.001, respectively. However, there was no difference between the RA and SS patients (P=0.762). IgA isotype of anti-BRAF antibody was measurable in the RA patients without RF, anti-CCP antibody or anti-keratin antibody (AKA) antibodies. The levels of IgA isotype of anti-BRAF antibody in the RA patients did not show any correlation with clinical features such as age and disease duration or laboratory parameters including ESR, CRP, RF, DAS28, anti-CCP antibody, immunoglobulin and BRAF protein levels. Compared with the clinical features and laboratory indexes of normal and elevated levels of IgA isotype of anti-BRAF antibody groups in the RA patients, there was no significant differences between the two groups in age, disease duration, ESR, CRP, RF, DAS28, anti-CCP antibody, immunoglobulin or BRAF protein levels. Conclusion: The elevated level of IgA isotype of anti-BRAF antibody in the RA patients showed that IgA isotype of anti-BRAF antibody might play a role in the pathogenesis of RA. Furthermore, detection of IgA isotype of anti-BRAF antibody in the serum negative RA patients showed that it might be helpful for the diagnosis of the serum negative RA patients.

Key words: Rheumatoid arthritis, v-raf murine sarcoma viral oncogene homologue B1, IgA isotype of anti-BRAF antibody

中图分类号: 

  • R593.22

表1

IgA型抗BRAF抗体在不同疾病组的AU值"

Disease type n AU P value
RA 61 62.4±43.5
SS 16 65.6±35.6 0.762
SLE 16 37.0±21.3 0.011
Gout 16 29.1±22.9 < 0.001
OA 21 21.9±17.2 < 0.001
Normal control 22 15.2±22.0 < 0.001

表2

IgA型抗BRAF抗体与RA患者临床及实验室指标的相关性分析"

Clinical index Correlation coefficient P value
Age -0.026 0.858
Duration 0.253 0.079
DAS28 -0.048 0.760
CRP 0.010 0.946
ESR 0.088 0.555
RF 0.207 0.153
Anti-CCP 0.053 1.725
IgA 0.143 0.419
IgM 0.129 0.469
IgG -0.088 0.614
BRAF protein 0.153 0.292

表3

IgA型抗BRAF抗体阳性组和阴性组RA患者实验室指标的比较"

Clinical index Antibody positive group Antibody negative group P value
Age/years 53.4±13.5 52.6±15.9 0.848
Duration/months 60.0 (1.0-360.0) 33.0 (1.0-240.0) 0.335
DAS28 4.56±1.27 4.60±0.62 0.879
CRP/(mg/dL) 2.11 (0.11-16.60) 2.58 (0.11-8.89) 0.818
ESR/(mm/h) 41.5 (2.0-110.0) 42.0 (6.0-84.0) 0.907
RF/(IU/mL) 115.0 (10.0-1 860.0) 50.0 (10.0-1 890.0) 0.126
Anti-CCP/(U/mL) 135.0 (7.0-500.0) 100.0 (7.0-500.0) 1.003
IgA/(mg/L) 3 340±1 340 3 340±1 610 0.719
IgM/(mg/L) 1 140 (610-3 990) 1 130 (210-2 640) 0.885
IgG/(mg/L) 15 440±6 700 17 680±7 850 0.371
BRAF protein/(ng/L) 9 557.5±8 208.9 6 865.6±5 368.4 0.196
1 Ikawa S , Fukui M , Ueyama Y , et al. B-raf, a new member of the raf family is activated by DNA rearrangement[J]. Mol Cell Biol, 1988, 8 (6): 2651- 2654.
2 Karhryn I . Raf protiens and cancer: B-Raf is identified as a mutational target[J]. Biochim Biophys Acta, 2003, 1653 (1): 25- 40.
3 Luo SF , Fang RY , Hsieh HL , et al. Involvement of MAPKs and NF-kappaB in tumor necrosis factor alpha-induced vascular cell adhesion molecule l expression in human rheumatoid arthritis synovial fibroblasts[J]. Arthritis Rheum, 2010, 62 (1): 105- 116.
doi: 10.1002/art.25060
4 Schett G , Zwerina J , Firestein G . The p38 mitogen-activated protein kinase (MAPK) pathway in rheumatoid arthritis[J]. Ann Rheum Dis, 2008, 67 (7): 909- 916.
doi: 10.1136/ard.2007.074278
5 Auger I , Balandraud N , Rak J , et al. New autoantigens in rheumatoid arthritis (RA): Screening 8268 protein arrays with sera from patients with RA[J]. Ann Rheum Dis, 2009, 68 (4): 591- 594.
doi: 10.1136/ard.2008.096917
6 Szekanecz Z , Soós L , Szabó Z , et al. Anti-citrullinated protein antibodies in rheumatoid arthritis: As good as it gets?[J]. Clin Rev Allergy Immunol, 2008, 34 (1): 26- 31.
doi: 10.1007/s12016-007-8022-5
7 Wang XP , Cheng QY , Gu MM , et al. Diagnostic accuracy of anti-keratin antibody for rheumatoid arthritis: A meta-analysis[J]. Clin Rheumatol, 2019, 38 (7): 1841- 1849.
doi: 10.1007/s10067-019-04464-x
8 Charpin C , Martin M , Balandraud N , et al. Autoantibodies to BRAF, a new family of autoantibodies associated with rheumatoid arthritis[J]. Arthritis Res Ther, 2010, 12 (5): R194.
doi: 10.1186/ar3165
9 张霞, 赵金霞, 孙琳, 等. 抗鼠科肉瘤病毒癌基因同源物B1抗体的检测及其在类风湿关节炎诊断中的意义[J]. 北京大学学报(医学版), 2012, 44 (2): 195- 198.
10 Woof JM , Mestecky J . Mucosal immunoglobulins[J]. Immunol Rev, 2005, 206, 64- 82.
doi: 10.1111/j.0105-2896.2005.00290.x
11 Thalhamer T , McGrath MA , Hamett MM . MAPKs and their relevance to arthritis and inflammation[J]. Rheumatology (Oxford), 2008, 47 (4): 409- 414.
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