Diagnostic value of serum IgG4 for IgG4-related diseases: A meta-analysis

doi:10.3969/j.issn.1004-583X.2021.07.002

Abstract

Abstract:

Objective To systematically evaluate the diagnostic value of serum IgG4 for IgG4-related diseases (IgG4-RD).Methods All related English studies to explore diagnostic value of serum IgG4 in IgG4-related diseases published in PubMed, EMBASE, Wangfang, Weipu and CNKI from January 1st, 2011 to January 1st, 2020 were searched by computer. Strict inclusion and exclusion criteria for literature screening and data extraction were established, the quality assessment was made by the quality evaluation tool (QUADAS-2), and meta-disc 1.4 software and the “Midas” command in STATA15.0 software were used for heterogeneity analysis and comprehensive quantitative synthesis. The pooled sensitivity, specificity, diagnostic advantage ratio, positive likelihood ratio and negative likelihood ratio were calculated respectively, and the relevant forest map was drawn, and the summary receiver operating curve (SROC) was fitted. The included literature were subgroup analyzed by region, disease type and sample size. Results A total of 17 articles and 17 095 patients were included in this meta-analysis. The cut-off value of IgG4 ranged from 1.3 to 1.44 g/L, the pooled sensitivity was 0.88(95%CI:0.81-0.93), the pooled specificity was 0.89(95%CI: 0.83-0.93), the pooled positive likelihood ratio was 8.3(95%CI: 5.1-13.7), the pooled negative likelihood ratio was 0.13(95%CI: 0.08-0.22) and the diagnostic advantage ratio was 62 (95%CI:25-153),respectively. The diagnostic value of serum IgG4>2×ULN (2.7-2.8 g/L) was reported in 11 studies, and the pooled sensitivity was 0.59(95%CI: 0.47-0.7), the pooled specificity was 0.96(95%CI: 0.94-0.97), the pooled positive likelihood ratio was 14.3(95%CI:9.1-22.7), the pooled negative likelihood ratio was 0.42(95%CI: 0.32-0.57), and the pooled diagnostic advantage ratio was 34(95%CI:17-69). Subgroup analysis showed that geography, whether only AIP patients were included, and sample size of IgG4-RD patients were all possible sources of heterogeneity. Deeks funnel plot showed no publication bias, and the sensitivity analysis revealed that the analysis result were stable and reliable. Conclusion Serum IgG4 has a high reference value in the diagnosis of IgG4-RD, and there is no significant diagnostic advantage in increasing the cut-off value to 2×ULN. This result still needs to be verified by more prospective and high-quality diagnostic tests.

Key words: immunoglobulin G, IgG4-related diseases, diagnosis, meta-analysis

CLC Number:

R392.11

Ding Hang, Liu Yuan, Zhang Lianfeng, Zhou Lin. Diagnostic value of serum IgG4 for IgG4-related diseases: A meta-analysis[J]. Clinical Focus, 2021, 36(7): 587-594.

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URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2021.07.002

https://huicui.hebmu.edu.cn/EN/Y2021/V36/I7/587

Figures/Tables 13

References 30

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作者	年份	国家	疾病类型	IgG4-RD (例)	对照组主要疾病	对照组 (例)	诊断标准	IgGA 临界值 (g/L)	纳入及排除(例)
									TP	FP	FN	TN
									Natioh^[6]	2012	日本	AIP	30	PC	19	JPS2006标准或HISORt 标准	1.35 2.8	26 23	4 1	4 7	15 59
Wang^[7]	2017	中国	IgG4-RD	25	AID;PC;AP;CCA;胆道结石;胆道狭窄;十二指肠乳头癌	298	IgG4-RD病理诊断共识	1.35	25	0	0	298
Su^[8]	2015	中国	IgG4-RD	12	AID;消化系统疾病;肾脏疾病;感染性疾病;肾脏疾病;心血管及呼吸系统疾病	945	IgG4-RD综合诊断标准	1.35	12	32	0	913
Yu^[9]	2015	中国	IgG4-RD	161	AID;恶性肿瘤;胰腺炎;过敏性疾病等	2 740	IgG4-RD综合诊断标准	1.35 2.7	138 121	635 161	23 40	2 105 2 579
Carruthers^[10]	2015	美国	IgG4-RD	72	AID;免疫缺陷病;感染性疾病;肺炎;胰胆管疾病;白血病	308	IgG4-RD病理诊断共识	1.35 2.7	65 25	125 28	7 47	183 280
Sánchez Castañón^[11]	2012	西班牙	AIP	12	PC	175	HISORt标准	1.3	7	10	5	165
Yang^[12]	2019	中国	IgG4-RD	68	风湿性疾病;肾脏疾病;肝胆管及胰腺、胃肠道疾病;造血系统疾病;呼吸系统及心血管疾病;恶性肿瘤	8 097	IgG4-RD综合诊断标准;IgG4-RD病理诊断共识	1.4 2.8	67 58	846 219	1 10	7 251 7 878
Culver^[13]	2016	英国	IgG4-RD	58	恶性肿瘤;PSC;PBC;胰腺炎;肝炎;AIH;AID;IBD	1 082	IgG4-RD综合诊断标准;HISORt标准;ICDC	1.4 2.8	48 33	166 41	10 25	916 1041
Li^[14]	2016	中国	IgG4-RD	242	AID;肾脏疾病;恶性肿瘤;胰腺炎以及健康人群	255	IgG4-RD综合诊断标准	1.35 2.7	196 150	39 16	46 92	216 239
Ohara^[15]	2013	日本	IgG4-SC	344	PSC;CCA;PC	504	2012日本IgG4-SC诊断标准;ICDC	1.35 2.7	309 235	41 8	35 109	463 496
Chang^[16]	2014	中国	AIP	162	PC	90	亚洲标准或ICDC或 HISORt标准	1.4 2.8	105 49	18 5	57 113	72 85
Boonstra^[17]	2014	荷兰	IgG4-SC	73	PSC	310	HISORt标准	1.4 2.8	66 51	45 7	7 22	265 303
Kaji^[18]	2012	日本	AIP	35	PC	71	ICDC;亚洲标准	1.35	32	2	3	69
Van Heerde^[19]	2014	荷兰	AIP	33	PC	53	ICDC或亚洲标准或 HISORt标准	1.4	28	10	5	43
Oseini^[20]	2011	美国	IgG4-SC	97	CCA	287	HISORt标准	1.4 2.8	69 41	37 11	28 56	250 276
Detlefsen^[21]	2018	丹麦	AIP	19	PC	17	ICDC	1.4 2.8	11 7	2 1	8 12	15 16
Yamamoto^[22]	2012	日本	IgG4-RD	102	风湿性疾病;支气管哮喘;IPF;肝硬化;慢性肝炎;恶性肿瘤;MCD以及健康组	299	HISORt标准	1.44	97	28	5	271

作者	年份	国家	疾病类型	IgG4-RD (例)	对照组主要疾病	对照组 (例)	诊断标准	IgGA 临界值 (g/L)	纳入及排除(例)
									TP	FP	FN	TN
									Natioh^[6]	2012	日本	AIP	30	PC	19	JPS2006标准或HISORt 标准	1.35 2.8	26 23	4 1	4 7	15 59
Wang^[7]	2017	中国	IgG4-RD	25	AID;PC;AP;CCA;胆道结石;胆道狭窄;十二指肠乳头癌	298	IgG4-RD病理诊断共识	1.35	25	0	0	298
Su^[8]	2015	中国	IgG4-RD	12	AID;消化系统疾病;肾脏疾病;感染性疾病;肾脏疾病;心血管及呼吸系统疾病	945	IgG4-RD综合诊断标准	1.35	12	32	0	913
Yu^[9]	2015	中国	IgG4-RD	161	AID;恶性肿瘤;胰腺炎;过敏性疾病等	2 740	IgG4-RD综合诊断标准	1.35 2.7	138 121	635 161	23 40	2 105 2 579
Carruthers^[10]	2015	美国	IgG4-RD	72	AID;免疫缺陷病;感染性疾病;肺炎;胰胆管疾病;白血病	308	IgG4-RD病理诊断共识	1.35 2.7	65 25	125 28	7 47	183 280
Sánchez Castañón^[11]	2012	西班牙	AIP	12	PC	175	HISORt标准	1.3	7	10	5	165
Yang^[12]	2019	中国	IgG4-RD	68	风湿性疾病;肾脏疾病;肝胆管及胰腺、胃肠道疾病;造血系统疾病;呼吸系统及心血管疾病;恶性肿瘤	8 097	IgG4-RD综合诊断标准;IgG4-RD病理诊断共识	1.4 2.8	67 58	846 219	1 10	7 251 7 878
Culver^[13]	2016	英国	IgG4-RD	58	恶性肿瘤;PSC;PBC;胰腺炎;肝炎;AIH;AID;IBD	1 082	IgG4-RD综合诊断标准;HISORt标准;ICDC	1.4 2.8	48 33	166 41	10 25	916 1041
Li^[14]	2016	中国	IgG4-RD	242	AID;肾脏疾病;恶性肿瘤;胰腺炎以及健康人群	255	IgG4-RD综合诊断标准	1.35 2.7	196 150	39 16	46 92	216 239
Ohara^[15]	2013	日本	IgG4-SC	344	PSC;CCA;PC	504	2012日本IgG4-SC诊断标准;ICDC	1.35 2.7	309 235	41 8	35 109	463 496
Chang^[16]	2014	中国	AIP	162	PC	90	亚洲标准或ICDC或 HISORt标准	1.4 2.8	105 49	18 5	57 113	72 85
Boonstra^[17]	2014	荷兰	IgG4-SC	73	PSC	310	HISORt标准	1.4 2.8	66 51	45 7	7 22	265 303
Kaji^[18]	2012	日本	AIP	35	PC	71	ICDC;亚洲标准	1.35	32	2	3	69
Van Heerde^[19]	2014	荷兰	AIP	33	PC	53	ICDC或亚洲标准或 HISORt标准	1.4	28	10	5	43
Oseini^[20]	2011	美国	IgG4-SC	97	CCA	287	HISORt标准	1.4 2.8	69 41	37 11	28 56	250 276
Detlefsen^[21]	2018	丹麦	AIP	19	PC	17	ICDC	1.4 2.8	11 7	2 1	8 12	15 16
Yamamoto^[22]	2012	日本	IgG4-RD	102	风湿性疾病;支气管哮喘;IPF;肝硬化;慢性肝炎;恶性肿瘤;MCD以及健康组	299	HISORt标准	1.44	97	28	5	271

分组	篇数	敏感度(95%CI)	P值	特异度(95%CI)	P值	DOR(95%CI)	AUC(95%CI)
总体	17	0.88(0.81-0.93)		0.89(0.83-0.93)		62(25-153)	0.95(0.92-0.96)
地区
亚洲欧美	10 7	0.93(0.83-0.97) 0.8(0.69-0.87)	<0.05	0.92(0.84-0.96) 0.85(0.77-0.91)	<0.05	156(30-816) 23(15-34)	0.97(0.96-0.98) 0.89(0.86-0.92)
疾病谱
IgG4-RD AIP	11 6	0.92(0.84-0.96) 0.77(0.64-0.86)	<0.05	0.90(0.81-0.95) 0.89(0.81-0.94)	0.09	101(26-388) 27(10-75)	0.96(0.94-0.98) 0.91(0.88-0.93)
样本量(例)
<100 >100	5 12	0.89(0.79-0.95) 0.85(0.75-0.92)	0.05	0.91(0.83-0.96) 0.86(0.79-0.9)	<0.05	85(24-304) 34(12-95)	0.96(0.94-0.97) 0.92(0.89-0.94)

分组	篇数	敏感度(95%CI)	P值	特异度(95%CI)	P值	DOR(95%CI)	AUC(95%CI)
总体	17	0.88(0.81-0.93)		0.89(0.83-0.93)		62(25-153)	0.95(0.92-0.96)
地区
亚洲欧美	10 7	0.93(0.83-0.97) 0.8(0.69-0.87)	<0.05	0.92(0.84-0.96) 0.85(0.77-0.91)	<0.05	156(30-816) 23(15-34)	0.97(0.96-0.98) 0.89(0.86-0.92)
疾病谱
IgG4-RD AIP	11 6	0.92(0.84-0.96) 0.77(0.64-0.86)	<0.05	0.90(0.81-0.95) 0.89(0.81-0.94)	0.09	101(26-388) 27(10-75)	0.96(0.94-0.98) 0.91(0.88-0.93)
样本量(例)
<100 >100	5 12	0.89(0.79-0.95) 0.85(0.75-0.92)	0.05	0.91(0.83-0.96) 0.86(0.79-0.9)	<0.05	85(24-304) 34(12-95)	0.96(0.94-0.97) 0.92(0.89-0.94)

分组	篇数	敏感度(95%CI)	P值	特异度(95%CI)	P值	DOR(95%CI)	AUC(95%CI)
总体	11	0.59(0.47-0.7)		0.96(0.94-0.97)		34(17-69)	0.95(0.92-0.96)
地区
亚洲欧美	6 5	0.67(0.52-0.80) 0.49(0.36-0.61)	0.1	0.96(0.94-0.98) 0.95(0.93-0.97)	<0.05	53(21-135) 20(8-51)	0.96(0.94-0.97) 0.89(0.86-0.92)
样本量(例)
<100 >100	7 4	0.59(0.43-0.73) 0.6(0.42-0.75)	0.72	0.96(0.94-0.97) 0.96(0.92-0.98)	<0.05	33(13-83) 32(12-87)	0.95(0.93-0.97) 0.94(0.91-0.96)