The characters of antibodies against PLA2R in healthy individuals and in the patient with PLA2R associated membranous nephropathy
Abstract Background Most primary membranous nephropathy (MN) is mediated by anti-phospholipase A2 receptor (PLA2R) antibodies. Recently, these antibodies have been revealed months to years before the disease's onset. Their production and pathogenicity need further investigation. Methods Anti-PL...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-023-01096-5 |
| _version_ | 1797850165792473088 |
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| author | Yan-jiao Cheng Miao Wang Jia Wang Zhao Cui Ming-hui Zhao |
| author_facet | Yan-jiao Cheng Miao Wang Jia Wang Zhao Cui Ming-hui Zhao |
| author_sort | Yan-jiao Cheng |
| collection | DOAJ |
| description | Abstract Background Most primary membranous nephropathy (MN) is mediated by anti-phospholipase A2 receptor (PLA2R) antibodies. Recently, these antibodies have been revealed months to years before the disease's onset. Their production and pathogenicity need further investigation. Methods Anti-PLA2R antibodies were purified from plasma of eight healthy individuals, 12 patients with PLA2R-related MN and negative circulating antibody (Ab-), and 18 patients with positive anti-PLA2R antibodies (Ab +), using affinity column coupled with recombinant human PLA2R. The antigen specificity, antibody amount, titer, IgG subclass, and affinity were assessed by Western blot, immunofluorescence, ELISA, and surface plasmon resonance. Results The natural anti-PLA2R antibodies recognized the conformational structure of PLA2R which locates on the cell membrane of podocytes. The amount of natural IgG was 0.12 ± 0.04 g/L, which accounted for 0.80% of total IgG and was lower than that of patients (2.36%, P < 0.001). The titer of natural antibodies was lower than that of patients in Ab- and Ab + groups (1:16 vs. 1:43 vs. 1:274, P < 0.001). IgG2(45.1%) was predominant in natural antibodies, while IgG4 was predominant in Ab + group (45.7 vs. 25.0%, P < 0.001). IgG1 was increasing from natural antibodies to Ab- and Ab + groups. The affinity of natural antibodies was lower than that of patients (KD: 641.0 vs. 269.0 vs. 99.6 nM, P = 0.002). The antibody titer, affinity, and IgG4 percentage were associated with the severity of proteinuria and the stages of membranous lesion. Conclusions The natural anti-PLA2R antibodies exist in healthy plasma. The antibody titer, IgG subclass, and affinity may participate in the pathogenesis of anti-PLA2R antibodies. |
| first_indexed | 2024-04-09T18:56:00Z |
| format | Article |
| id | doaj.art-718141be80604d0cbedabe42c4a80eb0 |
| institution | Directory Open Access Journal |
| issn | 2047-783X |
| language | English |
| last_indexed | 2024-04-09T18:56:00Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj.art-718141be80604d0cbedabe42c4a80eb02023-04-09T11:11:24ZengBMCEuropean Journal of Medical Research2047-783X2023-03-0128111110.1186/s40001-023-01096-5The characters of antibodies against PLA2R in healthy individuals and in the patient with PLA2R associated membranous nephropathyYan-jiao Cheng0Miao Wang1Jia Wang2Zhao Cui3Ming-hui Zhao4Renal Division, Institute of Nephrology, Key Laboratory of Renal Disease, Key Laboratory of CKD Prevention and Treatment, Peking University First Hospital, Peking University, Ministry of Health of China, Ministry of Education of ChinaRenal Division, Institute of Nephrology, Key Laboratory of Renal Disease, Key Laboratory of CKD Prevention and Treatment, Peking University First Hospital, Peking University, Ministry of Health of China, Ministry of Education of ChinaRenal Division, Institute of Nephrology, Key Laboratory of Renal Disease, Key Laboratory of CKD Prevention and Treatment, Peking University First Hospital, Peking University, Ministry of Health of China, Ministry of Education of ChinaRenal Division, Institute of Nephrology, Key Laboratory of Renal Disease, Key Laboratory of CKD Prevention and Treatment, Peking University First Hospital, Peking University, Ministry of Health of China, Ministry of Education of ChinaRenal Division, Institute of Nephrology, Key Laboratory of Renal Disease, Key Laboratory of CKD Prevention and Treatment, Peking University First Hospital, Peking University, Ministry of Health of China, Ministry of Education of ChinaAbstract Background Most primary membranous nephropathy (MN) is mediated by anti-phospholipase A2 receptor (PLA2R) antibodies. Recently, these antibodies have been revealed months to years before the disease's onset. Their production and pathogenicity need further investigation. Methods Anti-PLA2R antibodies were purified from plasma of eight healthy individuals, 12 patients with PLA2R-related MN and negative circulating antibody (Ab-), and 18 patients with positive anti-PLA2R antibodies (Ab +), using affinity column coupled with recombinant human PLA2R. The antigen specificity, antibody amount, titer, IgG subclass, and affinity were assessed by Western blot, immunofluorescence, ELISA, and surface plasmon resonance. Results The natural anti-PLA2R antibodies recognized the conformational structure of PLA2R which locates on the cell membrane of podocytes. The amount of natural IgG was 0.12 ± 0.04 g/L, which accounted for 0.80% of total IgG and was lower than that of patients (2.36%, P < 0.001). The titer of natural antibodies was lower than that of patients in Ab- and Ab + groups (1:16 vs. 1:43 vs. 1:274, P < 0.001). IgG2(45.1%) was predominant in natural antibodies, while IgG4 was predominant in Ab + group (45.7 vs. 25.0%, P < 0.001). IgG1 was increasing from natural antibodies to Ab- and Ab + groups. The affinity of natural antibodies was lower than that of patients (KD: 641.0 vs. 269.0 vs. 99.6 nM, P = 0.002). The antibody titer, affinity, and IgG4 percentage were associated with the severity of proteinuria and the stages of membranous lesion. Conclusions The natural anti-PLA2R antibodies exist in healthy plasma. The antibody titer, IgG subclass, and affinity may participate in the pathogenesis of anti-PLA2R antibodies.https://doi.org/10.1186/s40001-023-01096-5Membranous nephropathyPhospholipase A2 receptorNatural antibodiesAntibody titerIgG subclassAntibody affinity |
| spellingShingle | Yan-jiao Cheng Miao Wang Jia Wang Zhao Cui Ming-hui Zhao The characters of antibodies against PLA2R in healthy individuals and in the patient with PLA2R associated membranous nephropathy European Journal of Medical Research Membranous nephropathy Phospholipase A2 receptor Natural antibodies Antibody titer IgG subclass Antibody affinity |
| title | The characters of antibodies against PLA2R in healthy individuals and in the patient with PLA2R associated membranous nephropathy |
| title_full | The characters of antibodies against PLA2R in healthy individuals and in the patient with PLA2R associated membranous nephropathy |
| title_fullStr | The characters of antibodies against PLA2R in healthy individuals and in the patient with PLA2R associated membranous nephropathy |
| title_full_unstemmed | The characters of antibodies against PLA2R in healthy individuals and in the patient with PLA2R associated membranous nephropathy |
| title_short | The characters of antibodies against PLA2R in healthy individuals and in the patient with PLA2R associated membranous nephropathy |
| title_sort | characters of antibodies against pla2r in healthy individuals and in the patient with pla2r associated membranous nephropathy |
| topic | Membranous nephropathy Phospholipase A2 receptor Natural antibodies Antibody titer IgG subclass Antibody affinity |
| url | https://doi.org/10.1186/s40001-023-01096-5 |
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