抗Ro52抗体和抗Ro60抗体在结缔组织病中的临床价值分析

doi:10.3969/j.issn.1004-583X.2024.03.005

摘要/Abstract

摘要：

目的探讨抗Ro52抗体和抗Ro60抗体在结缔组织病(connective tissue disease, CTD)中的临床意义,分析其对结缔组织病相关间质性肺病(CTD associated interstitial lung disease, CTD-ILD)的风险预测价值。方法纳入2019年10月至2021年1月在河北医科大学第二医院风湿免疫科住院并明确诊断为CTD的患者785例,并收集其临床资料。依据患者抗Ro52抗体和抗Ro60抗体的表达情况分为4组:Ro52⁺Ro60^-组(n=94)、Ro52^-Ro60⁺组(n=80)、Ro52⁺Ro60⁺组(n=251)和Ro52^-Ro60^-组(n=360);依据有无ILD将患者分为两组:CTD合并ILD组(n=243)和CTD不合并ILD组(n=542)。比较各组临床资料差异,采用logistic逐步回归进行多因素分析,评估抗Ro52抗体和抗Ro60抗体对CTD,尤其CTD-ILD的临床风险评估。结果患者抗Ro52抗体和抗Ro60抗体表达情况存在差异,不同组别间一般资料、临床症状、细胞因子、免疫球蛋白、补体和自身抗体方面差异均有统计学意义(P<0.05)。男性发生ILD的概率增加了56.7%;年龄每增加1岁,发生ILD的风险将增加3.8%;抗Ro52⁺Ro60^-抗体的CTD患者比其他患者发生ILD的概率高。结论抗Ro52抗体阳性、男性和高龄是CTD患者发生ILD的独立危险因素。抗Ro52和抗Ro60抗体在CTD中作用复杂,应该替代传统的抗SSA抗体分别做为独立的抗体来进行检测。

关键词: 结缔组织疾病, 肺疾病,间质性, 抗Ro52抗体, 抗Ro60抗体

Abstract:

Objective To investigate the clinical significance of anti-Ro52 and anti-Ro60 antibodies in connective tissue disease (CTD), and to analyze their potential in risk prediction of CTD-associated interstitial lung disease (CTD-ILD). Methods A total of 785 patients diagnosed as CTD and hospitalized in the Department of Rheumatology and Immunology, the Second Hospital of Hebei Medical University from October 2019 to January 2021 were enrolled in this study. Their clinical and laboratory data were collected. According to the testing result for anti-Ro52 and anti-Ro60 antibodies, patients were assigned into anti-Ro52⁺anti-Ro60^- group (n=94), anti-Ro52^-anti-Ro60⁺ group (n=80), anti-Ro52⁺anti-Ro60⁺ group (n=251) and anti-Ro52^-anti-Ro60^- group (n=360). According to the presence or absence of ILD, patients were assigned into CTD with ILD group (n=243) and CTD without ILD group (n=542). Clinical data were compared between groups. Multivariable logistic step-wise regression was performed to assess the potential of anti-Ro52 and anti-Ro60 antibodies in predicting the risk of CTD, especially CTD-ILD. Results Titers of anti-Ro52 and anti-Ro60 antibodies varied among enrolled patients. Significant differences were detected in the general information, clinicalsymptoms, cytokines, immunoglobulins, complements and autoantibodies between groups (P<0.05). Compared with females, the incidence of ILD increased by 56.7% in males. The risk of ILD increased by 3.8% for each additional year of age. Patients in the anti-Ro52⁺anti-Ro60^- group had a higher risk of ILD than those in other groups. Conclusion Positivity for anti-Ro52 antibody, male and old age are independent risk factors for ILD in CTD patients. Anti-Ro52 and anti-Ro60 antibodies have a complicated role in CTD, both of which should be used to replace the detection of traditional anti-SSA antibodies as independent variables to be examined.

Key words: connective tissue disease, lung disease, interstitial, anti-Ro52 antibodies, anti-Ro60 antibodies

中图分类号:

R593.2

巩思静, 杨玉淑, 郭惠芳, 丁萌, 王炜, 高丽霞. 抗Ro52抗体和抗Ro60抗体在结缔组织病中的临床价值分析[J]. 临床荟萃, 2024, 39(3): 227-233.

Gong Sijing, Yang Yushu, Guo Huifang, Ding Meng, Wang Wei, Gao Lixia. Analysis of the clinical value for anti-Ro52 and anti-Ro60 antibodies in connective tissue disease[J]. Clinical Focus, 2024, 39(3): 227-233.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2024.03.005

https://huicui.hebmu.edu.cn/CN/Y2024/V39/I3/227

图/表 7

参考文献 28

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组别	例数	年龄 (岁)	男性 [例(%)]	临床症状[例(%)]
组别	例数	年龄 (岁)	男性 [例(%)]	发热	关节肿痛	肌痛/肌无力	皮疹	口干/眼干	光过敏	胸闷/气短	头晕/头痛
Ro52⁺Ro60^-组	94	53.10±15.68	11(11.7)	20(27.0)	32(43.2)	38(51.4)	24(32.9)	24(32.9)	2(2.7)	25(34.2)	3(4.1)
Ro52^-Ro60⁺组	80	45.75±17.06^*	7(8.8)	5(19.2)	13(50.0)	4(15.4)^*	4(15.4)	15(57.7)	1(3.8)	4(15.4)^*	0
Ro52⁺Ro60⁺组	251	42.39±14.77^*	18(7.2)	21(17.8)	47(40.2)	36(30.5)^*	27(23.5)	81(68.6)^*	1(0.9)	20(17.2)^*	8(7.0)
Ro52^-Ro60^-组	360	51.76±16.66^#△	77(21.4)^*#△	44(17.1)	195(75.6)^*#△	77(29.6)^*	60(23.2)	53(20.5)^#△	6(2.3)	52(20.1)	9(3.5)
F/χ²值		20.496	27.541	3.856	55.170	16.677	4.229	86.479	1.389	9.210	3.627
P值		<0.05	<0.05	0.277	<0.01	0.001	0.238	<0.01	0.708	0.027	0.305

组别	例数	年龄 (岁)	男性 [例(%)]	临床症状[例(%)]
组别	例数	年龄 (岁)	男性 [例(%)]	发热	关节肿痛	肌痛/肌无力	皮疹	口干/眼干	光过敏	胸闷/气短	头晕/头痛
Ro52⁺Ro60^-组	94	53.10±15.68	11(11.7)	20(27.0)	32(43.2)	38(51.4)	24(32.9)	24(32.9)	2(2.7)	25(34.2)	3(4.1)
Ro52^-Ro60⁺组	80	45.75±17.06^*	7(8.8)	5(19.2)	13(50.0)	4(15.4)^*	4(15.4)	15(57.7)	1(3.8)	4(15.4)^*	0
Ro52⁺Ro60⁺组	251	42.39±14.77^*	18(7.2)	21(17.8)	47(40.2)	36(30.5)^*	27(23.5)	81(68.6)^*	1(0.9)	20(17.2)^*	8(7.0)
Ro52^-Ro60^-组	360	51.76±16.66^#△	77(21.4)^*#△	44(17.1)	195(75.6)^*#△	77(29.6)^*	60(23.2)	53(20.5)^#△	6(2.3)	52(20.1)	9(3.5)
F/χ²值		20.496	27.541	3.856	55.170	16.677	4.229	86.479	1.389	9.210	3.627
P值		<0.05	<0.05	0.277	<0.01	0.001	0.238	<0.01	0.708	0.027	0.305

组别		例数	细胞因子(ng/L)
组别		例数	IL-1β		IL-2		IL-12p70		IL-17		IFN-α			IFN-γ		TNF-α
Ro52⁺Ro60^-组		94	8.39(2.76, 21.14)		2.24(1.39, 3.73)		1.14±0.63		2.30(1.37, 3.76)		3.17(1.46, 7.26)			6.83(2.40, 9.29)		3.68(1.88, 5.29)
Ro52^-Ro60⁺组		80	6.43(2.60, 16.00)		1.15(0.83, 1.52)^*		0.95±0.38		1.66(0.86, 1.74)^*		1.94(1.26, 3.79)^*			5.46(1.00, 9.53)		2.86(1.43, 4.07)
Ro52⁺Ro60⁺组		251	8.87(3.33, 20.97)		1.79(1.09, 2.71)^#		1.19±0.56^#		1.53(1.05, 2.64)^*#		2.85(1.64, 5.46)^#			7.02(3.21, 11.66)^#		2.81(1.52, 4.79)
Ro52^-Ro60^-组		360	8.74(2.66, 16.44)		1.44(0.99, 2.09)^*△		1.13±0.57^#		1.34(0.94, 1.91)^*△		1.76(1.24, 2.58)^*△			5.51(1.95, 10.17)^△		3.25(1.60, 5.62)
χ²/F/H值			4.077		45.406		3.093		40.924		49.390			8.370		5.365
P值			0.253		<0.01		0.027		<0.01		<0.01			0.033		0.147
组别	免疫指标(g/L)											自身抗体[例(%)]
组别	IgG			IgM		IgA		C3		C4		RF	抗CCP抗体		ANA		抗SSB抗体
Ro52⁺Ro60^-组	12.70(10.95, 15.20)			1.15(0.89, 1.45)		2.86(2.23, 3.60)		0.82±0.19		0.17(0.12, 0.24)		27(40.3)	10(27.8)		90(95.7)		2(2.1)
Ro52^-Ro60⁺组	13.60(10.55, 17.60)			1.00(0.70, 1.59)		2.93(2.19, 4.05)		0.63±0.27^*		0.12(0.08, 0.18)^*		18(29.5)	9(32.1)		80(100.0)		7(8.9)
Ro52⁺Ro60⁺组	18.40(13.63, 22.68)^*#			0.91(0.72, 1.17)^*		2.84(2.15, 3.78)		0.65±0.3^*		0.13(0.07, 0.19)^*		127(62.7)^*#	24(25.3)		249(99.6)^*		116(46.4)^*#
Ro52^-Ro60^-组	12.40(10.60, 15.80)^△			0.99(0.67, 1.38)^*		2.55(1.95, 3.33)		0.89±0.32^#△		0.20(0.13, 0.26)^#△		147(51.8)^#△	119(57.8)^*△		276(78.4)^*#△		0^*#△
χ²/F/H值	105.940			12.112		4.701		37.540		79.812		33.323	34.739		86.948		357.394
P值	<0.01			0.007		0.195		<0.01		<0.01		<0.01	<0.01		<0.01		<0.01

组别		例数	细胞因子(ng/L)
组别		例数	IL-1β		IL-2		IL-12p70		IL-17		IFN-α			IFN-γ		TNF-α
Ro52⁺Ro60^-组		94	8.39(2.76, 21.14)		2.24(1.39, 3.73)		1.14±0.63		2.30(1.37, 3.76)		3.17(1.46, 7.26)			6.83(2.40, 9.29)		3.68(1.88, 5.29)
Ro52^-Ro60⁺组		80	6.43(2.60, 16.00)		1.15(0.83, 1.52)^*		0.95±0.38		1.66(0.86, 1.74)^*		1.94(1.26, 3.79)^*			5.46(1.00, 9.53)		2.86(1.43, 4.07)
Ro52⁺Ro60⁺组		251	8.87(3.33, 20.97)		1.79(1.09, 2.71)^#		1.19±0.56^#		1.53(1.05, 2.64)^*#		2.85(1.64, 5.46)^#			7.02(3.21, 11.66)^#		2.81(1.52, 4.79)
Ro52^-Ro60^-组		360	8.74(2.66, 16.44)		1.44(0.99, 2.09)^*△		1.13±0.57^#		1.34(0.94, 1.91)^*△		1.76(1.24, 2.58)^*△			5.51(1.95, 10.17)^△		3.25(1.60, 5.62)
χ²/F/H值			4.077		45.406		3.093		40.924		49.390			8.370		5.365
P值			0.253		<0.01		0.027		<0.01		<0.01			0.033		0.147
组别	免疫指标(g/L)											自身抗体[例(%)]
组别	IgG			IgM		IgA		C3		C4		RF	抗CCP抗体		ANA		抗SSB抗体
Ro52⁺Ro60^-组	12.70(10.95, 15.20)			1.15(0.89, 1.45)		2.86(2.23, 3.60)		0.82±0.19		0.17(0.12, 0.24)		27(40.3)	10(27.8)		90(95.7)		2(2.1)
Ro52^-Ro60⁺组	13.60(10.55, 17.60)			1.00(0.70, 1.59)		2.93(2.19, 4.05)		0.63±0.27^*		0.12(0.08, 0.18)^*		18(29.5)	9(32.1)		80(100.0)		7(8.9)
Ro52⁺Ro60⁺组	18.40(13.63, 22.68)^*#			0.91(0.72, 1.17)^*		2.84(2.15, 3.78)		0.65±0.3^*		0.13(0.07, 0.19)^*		127(62.7)^*#	24(25.3)		249(99.6)^*		116(46.4)^*#
Ro52^-Ro60^-组	12.40(10.60, 15.80)^△			0.99(0.67, 1.38)^*		2.55(1.95, 3.33)		0.89±0.32^#△		0.20(0.13, 0.26)^#△		147(51.8)^#△	119(57.8)^*△		276(78.4)^*#△		0^*#△
χ²/F/H值	105.940			12.112		4.701		37.540		79.812		33.323	34.739		86.948		357.394
P值	<0.01			0.007		0.195		<0.01		<0.01		<0.01	<0.01		<0.01		<0.01

组别	例数	pSS是否合并ILD		PM/DM是否合并ILD		RA是否合并ILD		SLE是否合并ILD		SSc是否合并ILD
组别	例数	是	否	是	否	是	否	是	否	是	否
Ro52⁺Ro60^-组	94	9(9.6)	8(8.5)	28(29.8)	12(12.8)	5(5.3)	5(5.3)	6(6.4)	15(16.0)	4(4.2)	2(2.1)
Ro52^-Ro60⁺组	80	8(10.0)	6(7.5)	0	0	5(6.2)	3(3.8)	8(10.0)	48(60.0)	2(2.5)	0
Ro52⁺Ro60⁺组	251	28(11.2)	58(23.1)	9(3.5)	3(1.2)	3(1.2)	12(4.8)	12(4.8)	123(49.0)	1(0.4)	2(0.8)
Ro52^-Ro60^-组	360	10(2.8)	12(3.3)	30(8.3)	31(8.6)	46(12.8)	122(33.9)	21(5.8)	79(21.9)	8(2.3)	1(0.3)
χ²值		5.166		5.711		7.242		9.798		4.593
P值		0.160		0.058		0.065		0.020		0.204