Улога серумских антитела BAFF, CFB, MCP-1 и анти-ПЛА2R у процени ефикасности код пацијената са мембранозном нефропатијом
Серумски BAFF, CFB, MCP-1 и анти-ПЛА2R антитела код мембранозне нефропатије
Sažetak
Objective: Monocyte chemoattractant protein-1 (MCP-1), serum B-cell activating factor (BAFF), complement B factor (CFB), and anti-M-type phospholipase A2 receptor (PLA2R) antibodies are investigated in connection with membranous nephropathy (MN) and their roles in evaluating the efficacy of treatment.
Methods: 108 patients who were hospitalized to our hospital between January 2023 and June 2024 were chosen to serve as research participants. Patients were divided into remission and nonremission groups according to their clinical efficacy. The levels of serum BAFF, CFB, MCP-1 and anti-PLA2R antibodies in patients with positive and negative anti-PLA2R and different pathological stages were compared, and the clinical data of the remission group and the nonremission group were compared. The association between serum levels of BAFF, CFB, and MCP-1 and anti-PLA2R antibody levels in patients who tested positive for anti-PLA2R antibody. The predictive efficacy of serum anti-PLA2R antibodies, BAFF, CFB, and MCP-1 for nonremission in MN patients after therapy was evaluated using receiver operating characteristic (ROC) curves.
Results: There were 78 patients who were positive for anti-PLA2R antibodies and 30 patients who were negative for anti-PLA2R antibodies. The levels of serum BAFF, CFB, MCP-1 and anti-PLA2R antibodies in patients positive for anti-PLA2R antibodies were significantly greater than those in patients negative for anti-PLA2R antibodies (P<0.05). The comparison of the serum BAFF, CFB and MCP-1 levels in MN patients at different stages were as follows: stage I < stage II < stage III < stage IV. Serum BAFF, CFB, and MCP-1 in patients positive for anti-PLA2R antibodies were positively correlated with the level of anti-PLA2R antibodies (r=0.792, 0.823, 0.832, P<0.001). Spearman correlation analysis revealed that the levels of serum BAFF, CFB, and MCP-1 in MN patients were positively correlated with pathological stage (rs=0.758, 0.752, 0.717, P<0.001). The pathological stage and anti-PLA2R antibody, BAFF, CFB and MCP-1 levels in the nonremission group were significantly greater than those in the remission group (P<0.05). After treatment, elevated serum levels of MCP-1, CFB, and BAFF were risk factors for nonremission in MN patients (P<0.05). The ROC curve analysis revealed that the area under the curve for the combined prediction of nonremission in MN patients after treatment with serum BAFF, CFB and MCP-1 was 0.948, which was greater than the area under the curve for the individual prediction of anti-PLA2R antibody and BAFF, CFB and MCP-1 (Z=4.116, 3.059, 4.122, 4.116, P<0.05).
Conclusion: The levels of serum BAFF, CFB and MCP-1 in MN patients are related to the level of anti-PLA2R antibody, MN stage and therapeutic effect. Moreover, the combined detection of serum BAFF, CFB and MCP-1 has high predictive value for the nonremission of MN patients after treatment.
Reference
2.Murtas C, Bruschi M, Spinelli S, Kajana X, Verrina EE, Angeletti A, Caridi G, Candiano G, Feriozzi S, Prunotto M, Ghiggeri GM. Novel biomarkers and pathophysiology of membranous nephropathy: PLA2R and beyond. Clin Kidney J. 2023 Dec 11;17(1):sfad228. doi: 10.1093/ckj/sfad228. PMID: 38213493; PMCID: PMC10783244.
3.Barbour SJ, Fervenza FC, Induruwage D, Brenchley PE, Rovin B, Hladunewich MA, Reich HN, Lafayette R, Aslam N, Appel GB, Zand L, Kiryluk K, Liu L, Cattran DC; MENTOR Trial Investigators. Anti-PLA2R Antibody Levels and Clinical Risk Factors for Treatment Nonresponse in Membranous Nephropathy. Clin J Am Soc Nephrol. 2023 Oct 1;18(10):1283-1293. doi: 10.2215/CJN.0000000000000237. Epub 2023 Jul 20. PMID: 37471101; PMCID: PMC10578640.
4.Zhang Y, Zhou Y, Guan H, Yu M. Exploring PLA2R and HLA in membranous nephropathy: A narrative review of pathogenic mechanisms and emerging therapeutic potentials. Int J Biol Macromol. 2024 Oct 2;280(Pt 1):136200. doi: 10.1016/j.ijbiomac.2024.136200. Epub ahead of print. PMID: 39366594.
5.Xue C, Wang J, Pan J, Liang C, Zhou C, Wu J, Song S, Cui L, Zhang L, Liu Y, Dai B. Cyclophosphamide induced early remission and was superior to rituximab in idiopathic membranous nephropathy patients with high anti-PLA2R antibody levels. BMC Nephrol. 2023 Sep 22;24(1):280. doi: 10.1186/s12882-023-03307-x. PMID: 37740193; PMCID: PMC10517553.
6.Zhang P, Xu F, Liu X, Hu Z, Liang D, Liang S, Zhu X, Yang F, Zeng C. Clinicopathological features and outcomes of PLA2R-related membranous nephropathy with renal glycosuria. Clin Nephrol. 2024 Nov;102(5):273-284. doi: 10.5414/CN111362. PMID: 39099383.
7.Ragy O, Abass W, Kanigicherla DAK, Shinkins B, Bestall J, King N, Brenchley P, Smith A, Hamilton P. PLA2R autoantibodies, a multifaceted biomarker in nephrotic syndrome and membranous nephropathy. Nephrol Dial Transplant. 2025 Aug 1;40(8):1458-1469. doi: 10.1093/ndt/gfaf012. PMID: 39820570; PMCID: PMC12315804.
8.Tian T, Zheng J, Li Y, Guo Q, Jiang Y. Association between PLA2R gene polymorphism and idiopathic membranous nephropathy in Heilongjiang Chinese. Ann Transl Med. 2023 Feb 15;11(3):148. doi: 10.21037/atm-22-6648. Epub 2023 Feb 10. PMID: 36846001; PMCID: PMC9951016.
9.Allinovi M, Lugli G, Rossi F, Palterer B, Almerigogna F, Caroti L, Antognoli G, Cirami C. Accuracy of serum PLA2R antibody detected by indirect immunofluorescence in diagnosing biopsy-proven primary membranous nephropathy: a single-center experience and a systematic review of the literature. J Nephrol. 2023 Mar;36(2):281-283. doi: 10.1007/s40620-022-01528-1. Epub 2022 Dec 3. PMID: 36462140.
10.Pan Y, Chen WD, Liu L, Yang H, Chang B, Cui C. Clinical Features and Pathology of PLA2R and THSD7A-Associated Membranous Nephropathy: A Single-Center Study from China. Immunotargets Ther. 2024 Jul 25;13:385-398. doi: 10.2147/ITT.S450413. PMID: 39081263; PMCID: PMC11287465.
11.McDonnell T, Wu HHL, Sinha S, Chinnadurai R. The Role of PLA2R in Primary Membranous Nephropathy: Do We Still Need a Kidney Biopsy? Genes (Basel). 2023 Jun 26;14(7):1343. doi: 10.3390/genes14071343. PMID: 37510247; PMCID: PMC10380005.
12.Rovin BH, Ronco PM, Wetzels JFM, Adler SG, Ayoub I, Zaoui P, Han SH, Dudani JS, Gilbert HN, Patel UD, Manser PT, Jauch-Lembach J, Faulhaber N, Boxhammer R, Härtle S, Sprangers B. Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody-Positive Primary Membranous Nephropathy. Kidney Int Rep. 2024 Jun 20;9(9):2635-2647. doi: 10.1016/j.ekir.2024.06.018. PMID: 39291206; PMCID: PMC11403052.
13.Wu L, Li X, Yan J. Commentary: Machine learning developed an intratumor heterogeneity signature for predicting prognosis and immunotherapy benefits in cholangiocarcinoma. Transl Oncol. 2024 Jul;45:101995. doi: 10.1016/j.tranon.2024.101995. Epub 2024 May 9. PMID: 38789241.
14.Ramachandran R, Jha V, Bose B. Key Points in Managing PLA2R-Associated Membranous Nephropathy. Kidney Int Rep. 2024 May 27;9(8):2320-2322. doi: 10.1016/j.ekir.2024.05.028. PMID: 39156140; PMCID: PMC11328565.
15.Metuku R, Wynn AB, Santos R. Management and Treatment of Primary Membranous Nephropathy With a Positive PLA2R Marker. Cureus. 2024 Dec 3;16(12):e75057. doi: 10.7759/cureus.75057. PMID: 39759600; PMCID: PMC11698536.
16.Wu L, Chen X, Zeng Q, Lai Z, Fan Z, Ruan X, Li X, Yan J. NR5A2 gene affects the overall survival of LUAD patients by regulating the activity of CSCs through SNP pathway by OCLR algorithm and immune score. Heliyon. 2024 Mar 28;10(7):e28282. doi: 10.1016/j.heliyon.2024.e28282. PMID: 38601554; PMCID: PMC11004709.
17.Li X, Song D, Hao Y, Ren M, Guo Y, Zhao H, Wang Y, Tang L. Efficacy and safety of rituximab in patients with PLA2R associated membranous nephropathy and resolved HCV infection. Sci Rep. 2024 Sep 9;14(1):20981. doi: 10.1038/s41598-024-72082-y. PMID: 39251782; PMCID: PMC11383943.
18.Wu L, Zhong Y, Wu D, Xu P, Ruan X, Yan J, Liu J, Li X. Immunomodulatory Factor TIM3 of Cytolytic Active Genes Affected the Survival and Prognosis of Lung Adenocarcinoma Patients by Multi-Omics Analysis. Biomedicines. 2022 Sep 10;10(9):2248. doi: 10.3390/biomedicines10092248. PMID: 36140350; PMCID: PMC9496572.
19.Huang J, Huang Y, Zeng X, Zhang Y, Zhang J, Hong Q, Peng Y. Screening potential diagnostic biomarkers for PLA2R associated idiopathic membranous nephropathy by WGCNA analysis and LASSO algorithm. Ren Fail. 2025 Dec;47(1):2438859. doi: 10.1080/0886022X.2024.2438859. Epub 2025 Jan 13. PMID: 39806779; PMCID: PMC11734395.
20.Wu L, Li X, Qian X, Wang S, Liu J, Yan J. Lipid Nanoparticle (LNP) Delivery Carrier-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity. Vaccines (Basel). 2024 Feb 12;12(2):186. doi: 10.3390/vaccines12020186. PMID: 38400169; PMCID: PMC10891594.
21.Cheng YJ, Wang M, Wang J, Cui Z, Zhao MH. The characters of antibodies against PLA2R in healthy individuals and in the patient with PLA2R associated membranous nephropathy. Eur J Med Res. 2023 Mar 20;28(1):128. doi: 10.1186/s40001-023-01096-5. Erratum in: Eur J Med Res. 2023 Apr 5;28(1):148. doi: 10.1186/s40001-023-01110-w. PMID: 36935517; PMCID: PMC10026444.
22.Chen Y, Xu Y, Chen S, Yu Y, Zhu X, Chen J. The application of podocyte antigen PLA2R and anti-PLA2R antibody in the diagnosis and treatment of membranous nephropathy. Ren Fail. 2023;45(2):2264939. doi: 10.1080/0886022X.2023.2264939. Epub 2023 Oct 9. PMID: 37814415; PMCID: PMC10566392.
23.Guo Y, Ren M, Wang Y, Zhai Z, Yu L, Wang L, Tang L. Effect of rituximab in patients with PLA2R-associated membranous nephropathy and malignancy. Int Immunopharmacol. 2024 Jan 5;126:111327. doi: 10.1016/j.intimp.2023.111327. Epub 2023 Dec 5. PMID: 38056198.
24.Wu L, Li H, Liu Y, Fan Z, Xu J, Li N, Qian X, Lin Z, Li X, Yan J. Research progress of 3D-bioprinted functional pancreas and in vitro tumor models. International Journal of Bioprinting. 2024, 10(1), 1256. doi: 10.36922/ijb.1256.
25.Kaur P, Prabhahar A, Kumar A, Pal D, Kumar V, Sekar A, Jha V, Nada R, Sethi J, Divyaveer S, Rathi M, Kohli HS, Ramachandran R. Complementary medicine and phospholipase A2 receptor (PLA2R)-related membranous nephropathy-fortuitous or causal? Kidney Int. 2023 Feb;103(2):425-427. doi: 10.1016/j.kint.2022.11.008. PMID: 36681458.
26.Wu L, Liu Q, Ruan X, Luan X, Zhong Y, Liu J, Yan J, Li X. Multiple Omics Analysis of the Role of RBM10 Gene Instability in Immune Regulation and Drug Sensitivity in Patients with Lung Adenocarcinoma (LUAD). Biomedicines. 2023 Jun 29;11(7):1861. doi: 10.3390/biomedicines11071861. PMID: 37509501; PMCID: PMC10377220.
27.Ushio Y, Akihisa T, Karasawa K, Seki M, Kobayashi S, Miyabe Y, Kataoka H, Ito N, Taneda S, Akiyama S, Hebisawa A, Kawano M, Honda K, Hoshino J. PLA2R-positive membranous nephropathy in IgG4-related disease. BMC Nephrol. 2024 Feb 23;25(1):66. doi: 10.1186/s12882-024-03511-3. PMID: 38395839; PMCID: PMC10893645.
28.Wu L, Yang L, Qian X, Hu W, Wang S, Yan J. Mannan-Decorated Lipid Calcium Phosphate Nanoparticle Vaccine Increased the Antitumor Immune Response by Modulating the Tumor Microenvironment. J Funct Biomater. 2024 Aug 16;15(8):229. doi: 10.3390/jfb15080229. PMID: 39194667; PMCID: PMC11355305.
29.Qin Y, Wu Q, Sheng H, Li T, Liu X, Yang X, Lin B, Zhou X, Jin J, Wang L, Huang B, He Q, Hu Z. Quantitative detection of anti-PLA2R antibodies targeting different epitopes and its clinical application in primary membranous nephropathy. Clin Chem Lab Med. 2022 Nov 10;61(2):251-259. doi: 10.1515/cclm-2022-0720. PMID: 36351699.
30.Bajcsi D, Bitó L, Turkevi-Nagy S, Nyári T, Kemény É, Légrády P, Ábrahám G, Iványi B. The value of PLA2R antigen and IgG subclass staining relative to anti-PLA2R seropositivity in the differential diagnosis of membranous nephropathy. BMC Nephrol. 2023 Aug 7;24(1):230. doi: 10.1186/s12882-023-03273-4. PMID: 37550626; PMCID: PMC10408061.
31.Wu L, Zhong Y, Yu X, Wu D, Xu P, Lv L, Ruan X, Liu Q, Feng Y, Liu J, Li X. Selective poly adenylation predicts the efficacy of immunotherapy in patients with lung adenocarcinoma by multiple omics research. Anticancer Drugs. 2022 Oct 1;33(9):943-959. doi: 10.1097/CAD.0000000000001319. Epub 2022 Aug 9. PMID: 35946526; PMCID: PMC9481295.
32.Liu Z, Wan C, Cao Y, Liu S, Xu Z, Zhang C, Su H. Distribution spectrum and clinical significance of glomerular exostosin (EXT1) deposits in PLA2R-positive membranous nephropathy. J Nephrol. 2024 Jan;37(1):149-158. doi: 10.1007/s40620-023-01779-6. Epub 2023 Oct 26. PMID: 37882962.
33.Zhang W, Chen J, Yuan Y, Luo J, Zhou Z, Wang G. PM2.5-induced oxidative stress upregulates PLA2R expression in the lung and is involved in the pathogenesis of membranous nephropathy through extracellular vesicles. Front Pharmacol. 2024 Dec 18;15:1516111. doi: 10.3389/fphar.2024.1516111. PMID: 39744137; PMCID: PMC11688400.
34.Wu L, Zheng Y, Ruan X, Wu D, Xu P, Liu J, Wu D, Li X. Long-chain noncoding ribonucleic acids affect the survival and prognosis of patients with esophageal adenocarcinoma through the autophagy pathway: construction of a prognostic model. Anticancer Drugs. 2022 Jan 1;33(1):e590-e603. doi: 10.1097/CAD.0000000000001189. PMID: 34338240; PMCID: PMC8670349.
35.Guo H, Yao Y, Zhou J, Wang S, Wang Y, Zheng D. The cutoff value and prognosis of anti-PLA2R antibody for idiopathic membranous nephropathy: a single-center retrospective study in China. Ren Fail. 2023;45(2):2253922. doi: 10.1080/0886022X.2023.2253922. Epub 2023 Sep 19. PMID: 37724562; PMCID: PMC10512780.
36.Chaitanya Gunda K, Mathew GG, Balasubramanian S, Sunil Kumar KS. Clinical implications of serum anti-PLA2R levels and glomerular PLA2R deposits in primary membranous nephropathy. G Ital Nefrol. 2024 Apr 29;41(2):2024-vol2. PMID: 38695230.
37.Yang SF, Xie XF, Lu WH, Lan P, Liu H, Jin L. The association of serum anti-PLA2R antibody and glomerular PLA2R antigen staining with clinical manifestations and outcomes in membranous nephropathy. Clin Exp Nephrol. 2023 Dec;27(12):1060-1066. doi: 10.1007/s10157-023-02399-x. Epub 2023 Sep 5. PMID: 37668806.
38.Li X, Shen Y, Li Y, Ma L, Sun Q. Clinicopathological characteristics and outcomes of PLA2R related idiopathic membranous nephropathy in patients with seronegative PLA2R antibodies. Ren Fail. 2024 Dec;46(1):2297015. doi: 10.1080/0886022X.2023.2297015. Epub 2024 Jan 26. PMID: 38275176; PMCID: PMC10823883.
39.Sethi S, Fervenza FC. Membranous nephropathy-diagnosis and identification of target antigens. Nephrol Dial Transplant. 2024 Mar 27;39(4):600-606. doi: 10.1093/ndt/gfad227. PMID: 37863839.
40.Hua MR, Zhao YL, Yang JZ, Zou L, Zhao YY, Li X. Membranous nephropathy: Mechanistic insights and therapeutic perspectives. Int Immunopharmacol. 2023 Jul;120:110317. doi: 10.1016/j.intimp.2023.110317. Epub 2023 May 17. PMID: 37207447.
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