抗核抗体阳性类风湿关节炎的临床和实验室检查特点

doi:10.19723/j.issn.1671-167X.2020.06.006

摘要/Abstract

摘要：

目的:分析抗核抗体(anti-nuclear antibodies, ANA)阳性类风湿关节炎(rheumatoid arthritis,RA)患者的临床及实验室检查特征。方法:选择2013年1月—2018年12月于北京大学第三医院风湿免疫科住院的428例RA患者的临床及实验室检查资料,回顾性分析ANA阳性RA患者的临床和实验室检查指标的特点。统计学方法符合正态分布的定量资料采用t检验,非正态分布的定量资料采用Wilcoxon秩和检验。定性资料采用χ²检验,1≤理论频数<5采用校正四格表χ²检验,理论频数<1采用确切概率法。结果:收集到ANA阳性患者共231例(54%),ANA阳性组中女性占比明显多于ANA阴性组(82.7% vs. 63.5%, χ²=20.355,P<0.01);ANA阳性组出现跖趾关节受累(22.1%)低于ANA阴性组(33.0%, χ²=6.414,P<0.05),ANA阳性组中合并继发性干燥综合征(secondary Sj?gren’s syndrome, sSS)的比例显著高于ANA阴性组(19.5% vs. 4.1%, χ²=23.300,P<0.01);ANA阳性组合并类风湿因子(rheumatoid factor, RF)阳性(77.1% vs. 53.8%, χ²=25.743,P<0.01)及抗环瓜氨酸多肽(cyclic citrullinated peptide,CCP)抗体阳性(74.9% vs. 59.4%, χ²=11.694,P<0.01)的比例均显著高于阴性组。ANA阳性组免疫球蛋白G(immunoglobulin G,IgG)水平[(15.1±5.1) g/L vs. (13.8±5.3) g/L, t=2.359, P<0.05]及免疫球蛋白M(immunoglobulin M,IgM)水平[1.25(0.92) g/L vs.1.05(0.65) g/L, Z=-3.449, P<0.01]高于阴性组,而血红蛋白(hemoglobin, Hb)水平[(109.64±17.98) vs. (114.47±18.48) g/L,t=-2.734, P<0.01]、血小板(platelet, PLT)水平[(266.4×10⁹±104.6×10⁹) vs. (295.9×10⁹±100.1×10⁹) /L,t=-2.970, P<0.01]低于阴性组。结论:ANA阳性RA患者合并sSS的比例显著高于ANA阴性者,前者IgG水平更高,而Hb及PLT水平则更低。

关键词: 类风湿关节炎, 抗核抗体, 继发性干燥综合征, 类风湿因子, 抗环瓜氨酸多肽抗体

Abstract:

Objective: To analyse the clinical and laboratory characteristics of antinuclear antibody (ANA) positive rheumatoid arthritis (RA) patients. Methods: The clinical and laboratory data of 428 RA cases from Department of of Rheumatology and Immunology Peking University Third Hospital from Jan 2013 to Dec 2018 were collected and used to analyse characters between ANA positive group and ANA negative group. T test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency<5, chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency<1. Results: The number of ANA positive group was 231 (54%). The female rate was obviously higher in ANA positive group (82.7% vs. 63.5%, χ²=20.355,P<0.01). The rate of metatarsophalangeal joints (MTPJs) involvement was lower in ANA positive group (22.1%) than in ANA negative group (33.0) (χ²=6.414, P<0.05). The incidence of secondary Sj?gren’s syndrome (sSS) was much higher in ANA positive group(19.5% vs. 4.1%, χ²=23.300,P<0.01). The positivity of rheumatoid factor (RF), as well as the positivity of anti-cyclic citrullinated peptide(CCP) antibody was much higher in ANA positive group (77.1% vs. 53.8%, χ²=25.743,P<0.01, 74.9% vs. 59.4%, χ²=11.694,P<0.01, respectively). The levels of immunoglobulin G (IgG) and immunoglobulin M (IgM) of ANA positive group were higher [(15.1±5.1) g/L vs. (13.8±5.3) g/L, t=2.359, P<0.05, 1.25 (0.92) g/L vs. 1.05 (0.65) g/L, Z=-3.449, P<0.01, respectively]. But the levels of hemoglobin (Hb) and platelet (PLT) was lower in ANA positive group[ (109.64±17.98) vs. (114.47±18.48) g/L,t=-2.734, P<0.01; (266.4×10⁹±104.6×10⁹) vs. (295.9×10⁹±100.1×10⁹) /L,t=-2.970, P<0.01, respectively]. Conclusion: The incidence of sSS was obviously higher in ANA positive group than in ANA negative group. Serum IgG of ANA positive group was higher, but Hb and PLT were lower.

Key words: Rheumatoid arthritis, antinuclear antibody, Secondary Sj?gren's syndrome, Rheumatoid factor, anti-cyclic citrullinated peptide antibody

中图分类号:

R593.22

张警丰,叶修玲,段萌,周小利,姚中强,赵金霞. 抗核抗体阳性类风湿关节炎的临床和实验室检查特点[J]. 北京大学学报（医学版）, 2020, 52(6): 1023-1028.

Jing-feng ZHANG,Xiu-ling YE,Meng DUAN,Xiao-li ZHOU,Zhong-qiang YAO,Jin-xia ZHAO. Clinical and laboratory characteristics of rheumatoid arthritis with positive antinuclear antibody[J]. Journal of Peking University (Health Sciences), 2020, 52(6): 1023-1028.

图/表 5

表1

表2

表3

表4

表5

ANA阳性RA组与ANA阴性RA患者实验室检查指标的比较"

Group	ANA+	ANA-	t/Z/χ²	P
Number of cases	231	197
RF, n(%)	178 (77.1)	106 (53.8)	25.743	<0.001^*
anti-CCP antibody, n(%)	173 (74.9)	117 (59.4)	11.694	0.001^*
AKA, n(%)	51 (25.5)	30 (17.9)	3.107	0.078
WBC/(×10⁹/L), M(QR)	6.35 (3.56)	6.74 (2.64)	-1.955	0.051
Hb/(g/L), $x -$ ±s	109.6±18.0	114.5±18.5	-2.734	0.007^*
PLT/(×10⁹/L), $x -$ ±s	266.4±104.6	295.9±100.1	-2.970	0.003^*
IgG/(g/L), $x -$ ±s)	15.1±5.1	13.8±5.3	2.359	0.019^*
IgA/(g/L), M(QR)	3.01 (1.96)	2.89 (2.33)	-1.217	0.224
IgM/(g/L), M(QR)	1.25 (0.92)	1.05 (0.65)	-3.449	0.001^*
C3/(g/L), M(QR)	1.03 (0.35)	1.05 (0.33)	-0.719	0.472
C4/(g/L), $x -$ ±s	0.22±0.09	0.23±0.09	-1.299	0.195
ESR/(mm/h), M(QR)	44.0 (51.0)	42.0 (56.5)	-1.104	0.270
CRP/(mg/dL), M(QR)	2.05 (5.42)	2.40 (6.64)	-0.645	0.519

表5

参考文献 15

[1]	Kavanaugh A, Tomar R, Reveille J, et al. Guidelines for clinical use of the anti-nuclear antibody test and tests for specific autoantibodies to nuclear antigens[J]. Arch Pathol Lab Med, 2000,124(1):71-81. pmid: 10629135
[2]	Nishimura S, Nishiya K, Hisakawa N, et al. Positivity for antinuclear antibody in patients with advanced rheumatoid arthritis[J]. Acta Medica Okayama, 1996,50(5):261-265. doi: 10.18926/AMO/30501 pmid: 8914679
[3]	Torre IG, Mendez LM. Studies of antinuclear antibodies in rheumatoid arthritis[J]. J Rheumatol, 1982,9(4):603-606. pmid: 6182293
[4]	Aitcheson CT, Peebles C, Joslin F, et al. Characteristics of antinuclear antibodies in rheumatoid arthritis[J]. Arthritis Rheum, 1980,23(5):528-538. doi: 10.1002/art.1780230503 pmid: 6990933
[5]	Marques RC, Bogas M, Ramos F, et al. Prognostic value of antinuclear antibodies in juvenile idiopathic arthritis and anterior uveitis. Results from a systematic literature review[J]. Acta Reumatol Port, 2014,39(2):116-122. pmid: 24879943
[6]	Hügle B, Hinze C, Lainka E, et al. Development of positive antinuclear antibodies and rheumatoid factor in systemic juvenile idiopathic arthritis points toward an autoimmune phenotype later in the disease course[J]. Pediatr Rheumatol, 2014,12(1):28. doi: 10.1186/1546-0096-12-28
[7]	Fernandez SAV, Lobo AZC, Oliveira ZNP, et al. Prevalence of antinuclear autoantibodies in the serum of normal blood donors[J]. Rev Hosp Clin, 2003,58(6):315-319. doi: 10.1590/S0041-87812003000600005
[8]	Racoubian E, Zubaid RM, Shareefd MA, et al. Prevalence of antinuclear antibodies in healthy Lebanese subjects, 2008-2015: a cross-sectional study involving 10 814 subjects[J]. Rheumatol Int, 2016,36(9):1231-1236. pmid: 27432022
[9]	Bienenstock H. Rheumatoid plantar synovial cysts[J]. Ann Rheum Dis, 1975,34(1):98-99. doi: 10.1136/ard.34.1.98 pmid: 1124961
[10]	Antero DC, Parra AGM, Miyazaki FH, et al. Secondary Sjögren’s syndrome and disease activity of rheumatoid arthritis[J]. Rev Assoc Méd Bras(English Edition), 2011,57(3):313-316.
[11]	Al-Osami MH, Allawi AAM, Al-Saadawi TH. The association of smoking with the extra-articular manifestations in rheumatoid arthritis patients[J]. Postgrad Med J, 2013,12(1):146-152.
[12]	Kuller LH, Mackey RH, Walitt BT, et al. Rheumatoid arthritis in the women health initiative: methods and baseline evaluation[J]. Am J Epidemiol, 2014,179(7):917-926. doi: 10.1093/aje/kwu003 pmid: 24569640
[13]	Tellides G, Pober JS. Inflammatory and immune responses in the arterial media[J]. Circ Res, 2015,116(2):312-322. doi: 10.1161/CIRCRESAHA.116.301312 pmid: 25593276
[14]	Aghdashi MA, Khadir M, Dinparasti-Saleh R. Antinuclear antibodies and lupus-like manifestations in rheumatoid arthritis and ankylosing spondylitis patients at 4 months’ follow-up after treatment with infliximab and etanercept[J]. Curr Rheumatol Rev, 2020,16(1):61-66. doi: 10.2174/1573397115666190506152729 pmid: 31057111
[15]	Yukawa N, Fujii T, Ishikawa SK, et al. Correlation of antinuclear antibody and anti-double-stranded DNA antibody with clinical response to infliximab in patients with rheumatoid arthritis: a retrospective clinical study[J]. Arthritis Res Ther, 2011,13(6):R213. doi: 10.1186/ar3546 pmid: 22192852

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Group	Number of cases	Age/years, M(QR)	Gender(female), n(%)	Disease duration/years, M(QR)	Somking history, n(%)
ANA+	231	60.0(18.0)	191 (82.7)	5.0 (16.0)	36 (15.6)
ANA-	197	61.0(16.0)	125 (63.5)	5.0 (12.2)	46 (23.4)
Z/χ²		-0.450	20.355	-1.401	4.140
P		0.653	<0.001	0.161	0.042

Group	ANA+	ANA-	t/Z/χ²	P
Number of cases	231	197
DIPJs, n(%)	16 (6.9)	17 (8.6)	0.433	0.51
PIPJs, n(%)	155 (67.1)	138 (70.0)	0.429	0.513
MCPJs, n(%)	134 (58.0)	121 (61.4)	0.514	0.473
Wrist joints, n(%)	148 (64.1)	136 (69.0)	1.175	0.278
Elbow joints, n(%)	92 (39.8)	89 (45.2)	1.247	0.264
Shoulder joints, n(%)	88 (38.1)	77 (39.1)	0.044	0.834
TMJs, n(%)	4 (1.7)	7 (3.6)	1.409	0.235
Sternoclavicular joints, n(%)	2 (0.9)	1 (0.5)	0	1.000
Hip joints, n(%)	41 (17.7)	36 (18.3)	0.02	0.888
Knee joints, n(%)	165 (71.4)	136 (69.0)	0.292	0.589
Ankle joints, n(%)	114 (49.4)	107 (54.3)	1.049	0.306
MTPJs, n(%)	51 (22.1)	65 (33.0)	6.414	0.011
PIPJs(F), n(%)	23 (10.0)	22 (11.2)	0.166	0.684
DIPJs(F), n(%)	0 (0.0)	2 (1.0)		0.211
Tender joint count, M(QR)	11.0 (19.0)	9.0 (13.0)	-1.096	0.273
Swollen joint count, M(QR)	5.0 (10.0)	5.0 (12.0)	-0.055	0.956
Joint deformity, n(%)	75 (32.5)	65 (33.0)	0.013	0.908
Symmetry, n(%)	222 (96.1)	191 (97.0)	0.227	0.633
VAS, M(QR)	5.0 (5.5)	5.0 (5.0)	-1.317	0.188
DSA28, x±s	5.4±1.5	5.3±1.5	1.331	0.184

Group	Number of cases	Vasculitis, n(%)	Rheumatoid nodules, n(%)	Peripheral neuropathy, n(%)	Pericarditis, n(%)	Pleural effusion, n(%)	ILD, n(%)	Anemia, n(%)
ANA+	231	2 (0.9)	18 (7.8)	5 (2.2)	6 (2.6)	9 (3.9)	53 (22.9)	120 (51.9)
ANA-	197	0 (0.0)	10 (5.1)	4 (2.0)	0 (0.0)	4 (2.0)	47 (23.9)	92 (46.7)
χ²			1.283	0.000	3.481	1.257	0.05	1.171
P		0.502	0.257	1.000	0.062	0.262	0.824	0.279