Identification of plasma differential peptids in PLA2R1-related membranous nephropathy patients

doi:10.3969/j.issn.1673-8640.2023.03.004

Abstract

Abstract:

Objective To investigate the changes of plasma peptide profiles of M-type phospholipase A2 receptor（PLA2R1） -related membranous nephropathy. Methods Totally，28 patients with primary membranous nephropathy（PMN） and positive anti-PLA2R1 antibody（PMN group） and 28 healthy subjects（healthy control group） were enrolled. The plasma peptides were determined by nano-high performance liquid chromatography tandem mass spectrometry（nano-HPLC-MS/MS），and the differentially expressed peptides between PMN and healthy control groups were screened. The differentially expressed peptides were analyzed bioinformatically，and liquid chromatography tandem mass spectrometry（LC-MS/MS）was used to verify them. Spearman correlation analysis was used to evaluate the correlation between plasma C4b and anti-PLA2R1-IgG antibodies in PMN patients.Results A total of 903 peptides were found，and 31 of them were expressed differentially between PMN and healthy control groups，with 15 being down-regulated and 16 being up-regulated. Totally，8 of them were from C4b. Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway analysis revealed that the complement and coagulation cascade were primarily involved in the precursor proteins of differentially expressed peptides. According to the verification results，the plasma C4b level in PMN group was lower than that in healthy control group（P<0.001）. The results of Spearman correlation analysis showed that plasma C4b in PMN patients had no correlation with anti-PLA2R1-IgG antibodies（r=0.03，P=0.877）. Conclusions C4b could be a promising new biomarker in patients with PLA2R1-related membranous nephropathy.

Key words: Peptides, Complement, High performance liquid chromatography tandem mass spectrometry, Primary membranous nephropathy, M-type phospholipase A2 receptor

CLC Number:

R446.1

WANG Yajie, ZU Bailing, GAN Chenxin, WU Jiaoxiang, SHU Jie, HANG Chen, CHEN Minghui, LIN Fujun, HU Zhigang, HUANG Biao, SHENG Huiming. Identification of plasma differential peptids in PLA2R1-related membranous nephropathy patients[J]. Laboratory Medicine, 2023, 38(3): 223-229.

Figures/Tables 6

References 14

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组别	例数	抗PLA2R1-IgG抗体/（RU/mL）	抗PLA2R1-IgG4抗体/（ng/mL）	C3/（g/L）	C4/（g/L）
正常对照组	28	<14.00	<200.00	1.17±0.18	0.26±0.06
PMN组	28	151.70±124.70	10 910.50±4 799.80	1.26±0.23	0.31±0.17
t值		6.317	11.81	1.637	1.643
P值		<0.001	<0.001	0.107	0.106

组别	例数	抗PLA2R1-IgG抗体/（RU/mL）	抗PLA2R1-IgG4抗体/（ng/mL）	C3/（g/L）	C4/（g/L）
正常对照组	28	<14.00	<200.00	1.17±0.18	0.26±0.06
PMN组	28	151.70±124.70	10 910.50±4 799.80	1.26±0.23	0.31±0.17
t值		6.317	11.81	1.637	1.643
P值		<0.001	<0.001	0.107	0.106

基因名称	蛋白质登记号	多肽序列	PI	相对分子质量	fold change	P值
ACTR3B	ENST00000256001	VDCGTG	3.80	550.58	-8.85	0.008 8
C4b	ENST00000647698	QLNNRQIR	12.00	1 041.18	-3.92	0.038 6
FGA	ENST00000403106	FLAEGGGVR	6.00	905.02	-2.67	0.020 0
C4b	ENST00000647698	NGFKSHALQLN	8.76	1 228.37	-2.61	0.016 5
C4b	ENST00000647698	NGFKSHALQLNN	8.76	1 342.48	-2.59	0.047 5
C4b	ENST00000647698	NGFKSHALQLNNR	11.00	1 498.66	-2.13	0.000 6
C4b	ENST00000647698	SHALQLNNR	9.49	1 052.16	-2.01	0.033 5
ALB	ENST00000621628	KFQNALL	8.75	833.00	-1.96	0.011 3
C4b	ENST00000647698	SHALQLNNRQI	9.49	1 293.45	-1.89	0.012 7
SERPINF2	ENST00000324015	MEPLGRQLTSGP	5.75	1 285.48	-1.49	0.030 6
KMT2A	ENST00000389506	SKTSEKK	9.70	806.91	-1.49	0.043 7
C4b	ENST00000647698	TLEIPGN	4.00	742.83	-1.43	0.003 7
IFT52	ENST00000373030	AAGKAVP	8.80	612.73	-1.35	0.042 6
C4b	ENST00000647698	ALQLNNR	9.79	827.94	-1.25	0.000 8
CDH23	ENST00000224721	GKVIAN	8.75	600.72	-1.24	0.038 5

基因名称	蛋白质登记号	多肽序列	PI	相对分子质量	fold change	P值
ACTR3B	ENST00000256001	VDCGTG	3.80	550.58	-8.85	0.008 8
C4b	ENST00000647698	QLNNRQIR	12.00	1 041.18	-3.92	0.038 6
FGA	ENST00000403106	FLAEGGGVR	6.00	905.02	-2.67	0.020 0
C4b	ENST00000647698	NGFKSHALQLN	8.76	1 228.37	-2.61	0.016 5
C4b	ENST00000647698	NGFKSHALQLNN	8.76	1 342.48	-2.59	0.047 5
C4b	ENST00000647698	NGFKSHALQLNNR	11.00	1 498.66	-2.13	0.000 6
C4b	ENST00000647698	SHALQLNNR	9.49	1 052.16	-2.01	0.033 5
ALB	ENST00000621628	KFQNALL	8.75	833.00	-1.96	0.011 3
C4b	ENST00000647698	SHALQLNNRQI	9.49	1 293.45	-1.89	0.012 7
SERPINF2	ENST00000324015	MEPLGRQLTSGP	5.75	1 285.48	-1.49	0.030 6
KMT2A	ENST00000389506	SKTSEKK	9.70	806.91	-1.49	0.043 7
C4b	ENST00000647698	TLEIPGN	4.00	742.83	-1.43	0.003 7
IFT52	ENST00000373030	AAGKAVP	8.80	612.73	-1.35	0.042 6
C4b	ENST00000647698	ALQLNNR	9.79	827.94	-1.25	0.000 8
CDH23	ENST00000224721	GKVIAN	8.75	600.72	-1.24	0.038 5

基因名称	蛋白质登记号	多肽序列	PI	相对分子质量	fold change	P值
ZNF525	ENST00000491101	PPKKLGL	10.02	751.97	1.33	0.046 5
SMIM35	ENST00000636151	ISTLGLILG	5.52	886.10	1.36	0.037 2
C3orf20	ENST00000253697	QRGRGSP	12.00	756.82	1.40	0.012 5
DENND4C	ENST00000434457	TSISGLVP	5.19	772.90	1.42	0.047 6
ABHD15	ENST00000307201	AALALILAVL	5.57	967.26	1.43	0.044 6
HSD17B4	ENST00000509514	RGSFQVTRAAWEHMKKQKYG	10.45	2 408.77	2.97	0.009 1
BAHCC1	ENST00000675386	ALVAATIN	5.57	771.91	3.58	0.004 7
EIF2AK3	ENST00000303236	AYSGK	8.63	524.57	5.00	0.022 3
DONSON	ENST00000432378	KSTELPV	6.00	772.90	6.08	0.027 1
HP	ENST00000565574	LTTAKNL	8.75	759.90	8.21	0.024 2
ALB	ENST00000621628	IAFAQY	5.52	711.82	11.36	0.032 0
USP6	ENST00000574788	SKGRLRLP	12.01	926.13	12.09	0.004 5
SRPK3	ENST00000393786	IGAEYG	4.00	608.65	16.87	0.006 3
AGAP3	ENST00000622464	TTVKVPGKRLP	11.17	1 195.47	20.65	0.001 4
EFHB	ENST00000344838	ITEIKLPV	6.00	912.14	38.14	0.010 5
LPCAT1	ENST00000283415	AGRKPVRK	12.02	911.12	150.84	0.002 6