常见血红蛋白变异体对不同糖化血红蛋白检测系统的影响

doi:10.3969/j.issn.1673-8640.2024.12.015

摘要/Abstract

摘要：

目的评估6种临床常用糖化血红蛋白（HbA_1c）检测系统对血红蛋白（Hb）变异体的识别能力和定量检测结果的准确性。方法收集2020年12月—2022年12月上海嘉会国际医院和上海交通大学医学院附属第六人民医院HbA_1c常规检测中的疑似Hb变异体干扰样本245例。采用6种临床常用检测系统（5种为高效液相色谱法，1种为毛细管电泳法）检测疑似干扰样本，并采用测序法确认Hb变异体的类型。以cobas c513全自动糖化血红蛋白仪（简称cobas c513）的检测结果为标准，评估6种检测系统的准确性。结果 245例疑似Hb变异体干扰样本经测序验证，共检出Hb变异体干扰样本141例，检出Hb变异体11种（Hb G-Coushatta、Hb G-Taipei、Hb J-Bangkok、Hb D-Los Angeles、Hb Pyrgos、Hb Q-Thailand、Hb Queens、Hb Quong Sze、Hb C、Hb E、Hb S）。仅Hb D-Los Angeles和Hb S可被6种检测系统全部检出，其他9种Hb变异体各检测系统的识别能力各异。除Hb S外，6种检测系统检测其他10种Hb变异体干扰样本的结果与cobas c513均有一定的差异。结论目前临床常用的HbA_1c检测系统对大部分Hb变异体的识别能力不足。对于Hb变异体的干扰，可采用不同方法进行检测，必要时进行测序验证。

关键词: 糖化血红蛋白, 血红蛋白变异体, 高效液相色谱法, 毛细管电泳法

Abstract:

Objective To evaluate the recognition ability and the accuracy of quantitative determination results of 6 commonly used clinical glycated hemoglobin A_1c（HbA_1c） determination systems for hemoglobin（Hb） variants. Methods A total of 245 suspected Hb variant interference samples were collected from HbA_1c routine test in Shanghai Jiahui International Hospital and the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2020 to December 2022. Six commonly used clinical determination systems（5 systems were high performance liquid chromatography，and 1 system was capillary electrophoresis） were used to determine suspected interference samples，and the types of Hb variants were confirmed by sequencing method. Based on the results of cobas c513 automatic glycated hemoglobin analyzer，the accuracy of 6 determination systems was evaluated. Results Totally，245 suspected Hb variant interference samples were verified by sequencing，141 Hb variant interference samples were determined. Eleven Hb variants（Hb G-Coushatta，Hb G-Taipei，Hb J-Bangkok，Hb D-Los Angeles，Hb Pyrgos，Hb Q-Thailand，Hb Queens，Hb Quong Sze，Hb C，Hb E，Hb S） were determined. Only Hb D-Los Angeles and Hb S can be determined by all the 6 determination systems，and the determination systems for the other 9 Hb variants had different recognition abilities. Except for Hb S，the results of 6 determination systems for the interference samples of other 10 Hb variants were different from those of cobas c513. Conclusions The commonly used clinical HbA_1c determination system is not able to identify most of the Hb variants. For the interference of Hb variants，different methods can be used for determination and sequencing verification if necessary.

Key words: Glycated hemoglobin A_1c, Hemoglobin variant, High performance liquid chromatography, Capillary electrophoresis

中图分类号:

R446.1

宋蓓玲, 吴炯, 胡嘉华, 王煜非. 常见血红蛋白变异体对不同糖化血红蛋白检测系统的影响[J]. 检验医学, 2024, 39(12): 1219-1223.

SONG Beiling, WU Jiong, HU Jiahua, WANG Yufei. Influence of common hemoglobin variants on different glycated hemoglobin determination systems[J]. Laboratory Medicine, 2024, 39(12): 1219-1223.

图/表 3

参考文献 11

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序号	变异体名称	突变链	突变位点	样本数量
1	Hb G-Coushatta	β链	22 GAA→GCA	42
2	Hb G-Taipei	β链	22 GAA→GGA	28
3	Hb J-Bangkok	β链	56 GGC→GAC	13
4	Hb D-Los Angeles	β链	121 GAA→CAA	10
5	Hb Pyrgos	β链	83 GGC→GAC	10
6	Hb Q-Thailand	α链	74 GAC→CAC	9
7	Hb Queens	α链	34 CTG→CGG	7
8	Hb Quong Sze	α链	125 CTG→CCG	5
9	Hb C	β链	6 GAG→AAG	5
10	Hb E	β链	26 GAG→AAG	6
11	Hb S	β链	6 GAG→GTG	6

序号	变异体名称	突变链	突变位点	样本数量
1	Hb G-Coushatta	β链	22 GAA→GCA	42
2	Hb G-Taipei	β链	22 GAA→GGA	28
3	Hb J-Bangkok	β链	56 GGC→GAC	13
4	Hb D-Los Angeles	β链	121 GAA→CAA	10
5	Hb Pyrgos	β链	83 GGC→GAC	10
6	Hb Q-Thailand	α链	74 GAC→CAC	9
7	Hb Queens	α链	34 CTG→CGG	7
8	Hb Quong Sze	α链	125 CTG→CCG	5
9	Hb C	β链	6 GAG→AAG	5
10	Hb E	β链	26 GAG→AAG	6
11	Hb S	β链	6 GAG→GTG	6

检测系统	Hb G-Coushatta	Hb G-Taipei		Hb J-Bangkok		Hb D-Los Angeles	Hb Pyrgos	Hb Q-Thailand
D-100
干扰报警	E-Window	E-Window		不报警		D-Window	不报警	S-Window
异常峰位置/s	27.10	27.23				28.31		66.77
异常峰面积/%	37.54	38.73				39.96		39.96
G8
干扰报警	不报警	不报警		不报警		H-VD	不报警	H-V1
异常峰位置/s						1.01		1.16
异常峰面积/%						29.00		75.10
MQ-6000
干扰报警	变异体报警	变异体报警		变异体报警		变异体报警	不报警	变异体报警
异常峰位置/s	63.10	64.70		59.30		69.50		72.00
异常峰面积/%	48.14	48.38		70.96		39.38		38.72
MQ-8000
干扰报警	变异体报警	变异体报警		变异体报警		变异体报警	不报警	不报警
异常峰位置/s	57.80	57.90		54.50		62.80
异常峰面积/%	48.01	49.23		76.76		40.03
Variant Ⅱ
干扰报警	E-D报警	不报警		不报警		E-D报警	不报警	S报警
异常峰位置/s	1.85					1.91		1.98
异常峰面积/%	49.30					42.10		70.70
Capillarys 2
干扰报警	未知峰报警	未知峰报警		未知峰报警		未知峰报警	未知峰报警	未知峰报警
异常峰位置/s
异常峰面积/%	33.00	33.00		38.20		30.00	25.60	12.70
检测系统	Hb Queens	Hb Quong Sze	Hb C		Hb E	Hb S
D-100
干扰报警	S-Window	不报警	C-Window		E-Window	S-Window
异常峰位置/s	28.85		30.00		27.10	28.00
异常峰面积/%	30.16		17.46		37.58	18.69
G8
干扰报警	H-V1	不报警	H-V1		不报警	H-V1
异常峰位置/s	1.12		1.18			1.15
异常峰面积/%	9.20		14.60			16.00
MQ-6000
干扰报警	不报警	不报警	变异体报警		变异体报警	变异体报警
异常峰位置/s			84.10		62.10	71.50
异常峰面积/%			38.57		57.41	17.69
MQ-8000
干扰报警	不报警	不报警	变异体报警		变异体报警	变异体报警
异常峰位置/s			78.20		52.60	64.40
异常峰面积/%			18.76		55.51	19.36
检测系统	Hb Queens	Hb Quong Sze	Hb C		Hb E	Hb S
Variant Ⅱ
干扰报警	不报警	不报警	不报警		不报警	S报警
异常峰位置/s						1.95
异常峰面积/%						19.50
Capillarys 2
干扰报警	未知峰报警	未知峰报警	未知峰报警		未知峰报警	未知峰报警
异常峰位置/s
异常峰面积/%	34.80	38.20	6.80		33.20	12.40

检测系统	Hb G-Coushatta	Hb G-Taipei		Hb J-Bangkok		Hb D-Los Angeles	Hb Pyrgos	Hb Q-Thailand
D-100
干扰报警	E-Window	E-Window		不报警		D-Window	不报警	S-Window
异常峰位置/s	27.10	27.23				28.31		66.77
异常峰面积/%	37.54	38.73				39.96		39.96
G8
干扰报警	不报警	不报警		不报警		H-VD	不报警	H-V1
异常峰位置/s						1.01		1.16
异常峰面积/%						29.00		75.10
MQ-6000
干扰报警	变异体报警	变异体报警		变异体报警		变异体报警	不报警	变异体报警
异常峰位置/s	63.10	64.70		59.30		69.50		72.00
异常峰面积/%	48.14	48.38		70.96		39.38		38.72
MQ-8000
干扰报警	变异体报警	变异体报警		变异体报警		变异体报警	不报警	不报警
异常峰位置/s	57.80	57.90		54.50		62.80
异常峰面积/%	48.01	49.23		76.76		40.03
Variant Ⅱ
干扰报警	E-D报警	不报警		不报警		E-D报警	不报警	S报警
异常峰位置/s	1.85					1.91		1.98
异常峰面积/%	49.30					42.10		70.70
Capillarys 2
干扰报警	未知峰报警	未知峰报警		未知峰报警		未知峰报警	未知峰报警	未知峰报警
异常峰位置/s
异常峰面积/%	33.00	33.00		38.20		30.00	25.60	12.70
检测系统	Hb Queens	Hb Quong Sze	Hb C		Hb E	Hb S
D-100
干扰报警	S-Window	不报警	C-Window		E-Window	S-Window
异常峰位置/s	28.85		30.00		27.10	28.00
异常峰面积/%	30.16		17.46		37.58	18.69
G8
干扰报警	H-V1	不报警	H-V1		不报警	H-V1
异常峰位置/s	1.12		1.18			1.15
异常峰面积/%	9.20		14.60			16.00
MQ-6000
干扰报警	不报警	不报警	变异体报警		变异体报警	变异体报警
异常峰位置/s			84.10		62.10	71.50
异常峰面积/%			38.57		57.41	17.69
MQ-8000
干扰报警	不报警	不报警	变异体报警		变异体报警	变异体报警
异常峰位置/s			78.20		52.60	64.40
异常峰面积/%			18.76		55.51	19.36
检测系统	Hb Queens	Hb Quong Sze	Hb C		Hb E	Hb S
Variant Ⅱ
干扰报警	不报警	不报警	不报警		不报警	S报警
异常峰位置/s						1.95
异常峰面积/%						19.50
Capillarys 2
干扰报警	未知峰报警	未知峰报警	未知峰报警		未知峰报警	未知峰报警
异常峰位置/s
异常峰面积/%	34.80	38.20	6.80		33.20	12.40

检测系统	Hb G-Coushatta	Hb G-Taipei	Hb J-Bangkok	Hb D-Los Angeles	Hb Pyrgos	Hb Q-Thailand	Hb Queens	Hb Quong Sze	Hb C	Hb E	Hb S
cobas c513/例	42	38	13	10	10	9	7	5	5	6	6
D-100
r²值	0.97	0.96	0.80	1.00	0.01	0.59	0.99	0.99	1.00	0.99	0.99
不一致例数^①/例	0	6	13	0	10	9	0	0	0	0	0
G8
r²值	0.91	0.90	0.97	0.97	0.80	0.94	0.95	0.87	1.00	0.82	1.00
不一致例数^①/例	0	28	12	3	10	1	0	5	0	6	0
MQ-6000
r²值	0.98	0.70	0.88	0.99	0.32	0.86	0.64	0.73	0.99	1.00	0.99
不一致例数^①/例	0	4	12	3	10	6	6	5	0	0	0
MQ-8000
r²值	1.00	0.97	0.98	0.98	—	1.00	0.81	—	0.99	1.00	0.99
不一致例数^①/例	0	3	13	6	10	0	6	5	0	0	0
Variant Ⅱ
r²值	0.75	0.74	0.97	0.99	0.94	0.92	0.89	1.00	0.88	0.93	1.00
不一致例数^①/例	42	28	13	0	10	7	7	0	3	4	0
Capillarys 2
r²值	0.95	0.77	1.00	0.96	0.99	1.00	0.78	0.94	0.99	1.00	0.99
不一致例数^①/例	0	5	0	0	0	0	5	0	0	0	0