Генетические детерминанты развития и течения мембранозной нефропатии
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Недавно были идентифицированы два основных подоцитарных антигена, участвующих в патогенезе идиопатической МН (ИМН): рецептор фосфолипазы А2 М-типа (phospholipase A2 receptor – PLA2R) и домен тромбоспондина 1-го типа, содержащий 7А (thrombospondin type-1 domain containing 7A – THSD7A). Обнаружение циркулирующих специфических антител к этим антигенам изменило подход к диагностике и лечению ИМН. Тем не менее вопрос о том, что определяет выработку данных антител, остается открытым. Обсуждается роль генетических факторов. В настоящем обзоре представлены результаты исследований, продемонстрировавших значимые ассоциации между определенными генетическими вариантами (в первую очередь генов HLA и PLA2R1) и ИМН.
Ключевые слова: идиопатическая мембранозная нефропатия, рецептор фосфолипазы А2 М-типа (PLA2R), главный комплекс гистосовместимости человека (HLA), гены HLA класса II, ген PLA2R1.
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Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults and is classified as either primary (idiopatic) or secondary MN according to underlying etiology (the later result from some known disease such as systemic autoimmune diseases, infections, malignancies, drugs, etc). In recent years, phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were identified as two major podocytic antigens involved in the pathogenesis of idiopatic MN (IMN). And the discovery of circulating antibodies specific for these target antigens has transformed the diagnostic workup and significally improved management of IMN. However why do such antibodies develop is not conclusively established. The role of underlying genetic factors is discussed. The review presents the results of recent studies, that have shown significant associations of specific genetic factors (particularly human leucocyte antigen class II and PLA2R1 genes) with IMN.
Keywords: idiopathic membranous nephropathy, phospholipase A2 receptor (PLA2R), Human Leukocyte Antigens (HLA), gene,
МРС class II, PLA2R1.
2. Polanco N, Gutiérrez E, Covarsí A, Ariza F, Carreño A, Vigil A, Baltar J, Fernández-Fresnedo G, Martín C, Pons S, Lorenzo D, Bernis C, Arrizabalaga P, Fernández-Juárez G, Barrio V, Sierra M, Castellanos I, Espinosa M, Rivera F, Oliet A, Fernández-Vega F, Praga M, Grupo de Estudio de las Enfermedades Glomerulares de la Sociedad Española de Nefrología. Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy. J Am SocNephrol. 2010;21(4):697-704.
doi: 10.1681/ASN.2009080861
3. Glassock RJ. The pathogenesis of idiopathic membranous nephropathy: a 50 year odyssey. Am J Kidney Dis. 2010;56(1):157-67. doi:10.1053/ j.ajkd.2010.01.008
4. Kerjaschki D. Pathomechanisms and molecular basis of membranous nephropathy. Lancet. 2004;364(9441):1194-6. doi:10.1016/S0140-6736 (04)17154-7
5. Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009;361(1):11-21. doi: 10.1056/NEJMoa0810457
6. Debiec H, Ronco P. PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy. N Engl J Med. 2011;364(7):689-90. doi: 10.1056/NEJMc1011678
7. Ronco P, Debiec H. Updates in renal medicine 1. Pathophysiological advances in membranous nephropathy: time for a shift in patient’s care. Lancet. 2015;385(9981):1983-92. doi: 10.1016/S0140-6736(15)60731-0
8. Sinico RA, Mezzina N, Trezzi B, Ghiggeri GM, Radice A. Immunology of membranous nephropathy: From animal models to humans. Clin Exp Immunol. 2016;183(2):157-65. doi: 10.1111/cei.12729
9. Francis JM, Beck LH Jr, Salant DJ. Membranous nephropathy: A journey frombench to bedside. Am J Kidney Dis. 2016;68(1):138-47. doi:10. 1053/j.ajkd.2016.01.030
10. Tomas NM, Beck LH Jr, Meyer-Schwesinger C, Seitz-Polski B, Ma H, Zahner G, et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl JMed. 2014;371(24):2277-87. doi: 10.1056/NEJMoa1409354
11. Wang CH, Su PT, Du XY, Kuo MW, Lin CY, Yang CC, et al. Thrombospondin type I domain containing 7A (THSD7A) mediates endothelial cell migration and tube formation. J Cell Physiol. 2010;222(3): 685-94. doi: 10.1002/jcp.21990
12. Larsen CP, Cossey LN, Beck LH. THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity. Mod Pathol. 2016;29(4):421-6. doi:10.1038/modpathol.2016.32
13. Klouda PT, Manos J, Acheson EJ, Dyer PA, Goldby FS, Harris R, et al. Strong association between idiopathic membranous nephropathy and HLA-DRW3. Lancet. 1979;13;2(8146):770-1.
14. Le Petit JC, Laurent B, Berthoux FC. HLA-DR3 and idiopathic membranous nephritis (IMN) association. Tissue Antigens. 1982;20:227-8. doi: 10.1111/j.1399-0039.1982.tb00350.x
15. Vaughan RW, Demaine AG, Welsh KI. A DQA1 allele is strongly associated with idiopathic membranous nephropathy. Tissue Antigens. 1989;34(5):261-9. doi: 10.1111/j.1399-0039.1989.tb01741.x
16. Ogahara S, Naito S, Abe K, Michinaga I, Arakawa K. Analysis of HLA class II genes in Japanese patients with idiopathic membranous glomerulonephritis. Kidney Int. 1992;41(1):175-82. doi: 10.1038/ki. 1992.24
17. Chevrier D, Giral M, Perrichot R, Latinne D, Coville P, Muller JY, et al. Idiopathic and secondary membranous nephropathy and polymorphism at TAP1 and HLA-DMA loci. Tissue Antigens. 1977;50:164-9. doi: 10.1111/j.1399-0039.1997.tb02855.x
18. Robinson J, Waller MJ, Parham P, Groot N, Bontrop R, Kennedy LJ, et al. IMGT/HLA and IMGT/MHC: sequence databases for the study of the major histocompatibility complex. NucleicAcids Res. 2003;31(1):311-4. doi: 10.1093/nar/gkg070
19. Хаитов Р.М., Алексеев Л.П. Система генов HLA и регуляция иммунного ответа. Аллергия, астма и клиническая иммунология. 2000;(8):7-16 [Khaitov RM, Alexeev LP. HLA gene system and regulation of immune response. Allergiya, Astma i Klinicheskaya Immunologiya. 2000;(8):7-16 (In Russ.)].
20. Horton R, Gibson R, Coggill P, et al. Variation analysis and gene annotation of eight MHC haplotypes: the MHC Haplotype Project. Immunogenetics. 2008;60(1):1-18. doi: 10.1007/s00251-007-0262-2
21. Kiryluk K, Li Y, Scolari F, Sanna-Cherchi S, Choi M, Verbitsky M,
et al. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat Genet. 2014;46(11):1187-96. doi: 10.1038/ng.3118
22. Suranyi MG, Guasch A, Hall B, Myers BD. Elevated levels of tumor necrosis factor- α in the nephrotic syndrome in humans. Am J Kidney Dis. 1993;21:251-9. doi: 10.1016/S0272-6386(12)80742-6
23. Honkanen E, von Willebrand E, Teppo AM, Tornroth T, Gronhagen-Riska C. Adhesion molecules and urinary tumor necrosis factor-α in idiopathic membranous glomerulonephritis. Kidney Int. 1998;53(4): 909-17. doi: 10.1111/j.1523-1755.1998.00833.x
24. Kroeger KM, Carville KS, Abraham LJ. The -308 tumor necrosis factor-α promoter polymorphism effects transcription. Mol Immunol. 1997;34(5):391-9. doi: 10.1016/S0161-5890(97)00052-7
25. Bouma G, Crusius JB, Oudkerk Pool M, Kolkman JJ, von Blom-
berg BM, Kostense PJ, et al. Secretion of tumour necrosis factor-α and lymphotoxin-α in relation to polymorphisms in the TNF genes and HLA-DR alleles. Relevance for inflammatory bowel disease. Scand J Immunol. 1996;43(4):456-63. doi: 10.1046/j.1365-3083.1996.d01-65.x
26. Bantis C, Heering PJ, Aker S, Siekierka M, Kuhr N, Grabensee B, et al. Tumor necrosis factor-alpha gene G-308A polymorphism is a risk factor for the development of membranous glomerulonephritis. Am J Nephrol. 2006;26:12-5. doi: 10.1159/000090706
27. Liu YH, Chen CH, Chen SY, Lin YJ, Liao WL, Tsai CH, et al. Association of phospholipase A2 receptor 1 polymorphisms with idiopathic membranous nephropathy in Chinese patients in Taiwan. J Biomed Sci. 2010;17:81.
28. Kim S, Chin HJ, Na KY, Kim S, Oh J, Chung W, et al. Progressive Renal Disease and Medical Informatics and Genomics Research
(PREMIER) members: Single nucleotide polymorphisms in the phospholipase A2 receptor gene are associated with genetic susceptibility to idiopathic membranous nephropathy. Nephron Clin Pract. 2011; 117(3):c253-8. doi: 10.1159/000320194
29. Stanescu HC, Arcos-Burgos M, Medlar A, Bockenhauer D, Kottgen A, Dragomirescu L, Voinescu C, et al. Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy. N Engl J Med. 2011;364(7):616-26. doi: 10.1056/NEJMoa1009742
30. Strange A, Capon F, Spencer CC, Knight J, Weale ME, Allen MH, et al. Genetic Analysis of Psoriasis Consortium and the Wellcome Trust Case Control Consortium 2. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet. 2010;42(11):985-90. doi: 10.1038/ng.694
31. Smyth DJ, Cooper JD, Howson JM, Walker NM, Plagnol V, Ste-
vens H, et al. PTPN22 Trp620 explains the association of chromosome 1p13 with type 1 diabetes and shows a statistical interaction with HLA class II genotypes. Diabetes. 2008;57(6):1730-7. doi: 10.2337/
db07-1131
32. Lv J, Hou W, Zhou X, Liu G, Zhou F, Zhao N, et al. Interaction between PLA2R1 and HLA-DQA1 variants associates with anti-PLA2R antibodies and membranous nephropathy. J Am Soc Nephrol. 2013;24(8):1323-9. doi: 10.1681/ASN.2012080771
33. Bullich G, Ballarín J, Oliver A, Ayasreh N, Silva I, Santín S, et al. HLA-DQA1 and PLA2R1 polymorphisms and risk of idiopathic membranous nephropathy. Clin J Am Soc Nephrol. 2014;9(2):335-43. doi: 10.2215/CJN.05310513
34. Saeed M, Beggs ML, Walker PD, Larsen CP. PLA2R-associated membranous glomerulopathy is modulated by common variants in PLA2R1 and HLA-DQA1 genes. Genes Immun. 2014 Dec;15(8):556-61. doi: 10.1038/gene.2014.50
35. Sekula P, Li Y, Stanescu HC, Wuttke M, Ekici AB, Bockenhauer D,
et al.; GCKD Investigators. Genetic risk variants for membranous nephropathy: Extension of and association with other chronic kidney disease aetiologies. Nephrol Dial Transplant. 2017;32(2):325-32.
doi: 10.1093/ndt/gfw001
36. Ramachandran R, Kumar V, Kumar A, Yadav AK, Nada R, Kumar H, et al. PLA2R antibodies, glomerular PLA2R deposits and variations in PLA2R1 and HLA-DQA1 genes in primary membranous nephropathy in South Asians. Nephrol Dial Transplant. 2016;31(9):1486-93.
doi: 10.1093/ndt/gfv399
37. Kaga H, Komatsuda A, Omokawa A, Okuyama S, Mori K, Wakui H, Takahashi N. Analysis of PLA2R1 and HLA-DQA1 sequence variants in Japanese patients with idiopathic and secondary membranous nephropathy. Clin Exp Nephrol. 2018 Apr;22(2):275-82. doi: 10.1007/ s10157-017-1471-0
38. Zeng CH, Chen HM, Wang RS, Chen Y, Zhang SH, Liu L, et al. Etiology and clinical characteristics of membranous nephropathy in Chinese patients. Am J Kidney Dis. 2008 Oct;52(4):691-8.
doi: 10.1053/j.ajkd.2008.06.006
39. Hanko JB, Mullan RN, O’Rourke DM, McNamee PT, Maxwell AP, Courtney AE. The changing pattern of adult primary glomerular disease. Nephrol Dial Transplant. 2009 Oct;24(10):3050-4. doi: 10.1093/ ndt/gfp254
40. Coenen MJ, Hofstra JM, Debiec H, Stanescu HC, Medlar AJ, Stengel B, et al. Phospholipase A2 receptor (PLA2R1) sequence variants in idiopathic membranous nephropathy. J Am SocNephrol. 2013;24(4): 677-83. doi: 10.1681/ASN.2012070730
41. 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature. 2015;526(7571):68-74. doi: 10.1038/nature15393
42. Cui Z, Xie LJ, Chen FJ, Pei ZY, Zhang LJ, Qu Z, et al. MHC class II risk alleles and amino acid residues in idiopathic membranous nephropathy. J Am Soc Nephrol. 2017;28(5):1651-64.
doi: 10.1681/ASN. 2016020114
43. Le WB, Shi JS, Zhang T, Liu L, Qin HZ, Liang S, et al. HLA-DRB1*15:01 and HLADRB3*02:02 in PLA2R-related membranous nephropathy. J Am Soc Nephrol. 2017;28(5):1642-50. doi: 10.1681/ ASN.2016060644
44. Kanigicherla D, Gummadova J, McKenzie EA, Roberts SA, Harris S, Nikam M, et al. Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy. Kidney International. 2013;83:940-8. doi: 10.1038/ki.2012.486
________________________________________________
1. Beck LH Jr, Salant DJ. Membranous nephropathy: from models to man. J Clin Invest. 2014;124(6):2307‑14. doi: 10.1172/JCI72270
2. Polanco N, Gutiérrez E, Covarsí A, Ariza F, Carreño A, Vigil A, Baltar J, Fernández-Fresnedo G, Martín C, Pons S, Lorenzo D, Bernis C, Arrizabalaga P, Fernández-Juárez G, Barrio V, Sierra M, Castellanos I, Espinosa M, Rivera F, Oliet A, Fernández-Vega F, Praga M, Grupo de Estudio de las Enfermedades Glomerulares de la Sociedad Española de Nefrología. Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy. J Am SocNephrol. 2010;21(4):697-704.
doi: 10.1681/ASN.2009080861
3. Glassock RJ. The pathogenesis of idiopathic membranous nephropathy: a 50 year odyssey. Am J Kidney Dis. 2010;56(1):157-67. doi:10.1053/ j.ajkd.2010.01.008
4. Kerjaschki D. Pathomechanisms and molecular basis of membranous nephropathy. Lancet. 2004;364(9441):1194-6. doi:10.1016/S0140-6736 (04)17154-7
5. Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009;361(1):11-21. doi: 10.1056/NEJMoa0810457
6. Debiec H, Ronco P. PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy. N Engl J Med. 2011;364(7):689-90. doi: 10.1056/NEJMc1011678
7. Ronco P, Debiec H. Updates in renal medicine 1. Pathophysiological advances in membranous nephropathy: time for a shift in patient’s care. Lancet. 2015;385(9981):1983-92. doi: 10.1016/S0140-6736(15)60731-0
8. Sinico RA, Mezzina N, Trezzi B, Ghiggeri GM, Radice A. Immunology of membranous nephropathy: From animal models to humans. Clin Exp Immunol. 2016;183(2):157-65. doi: 10.1111/cei.12729
9. Francis JM, Beck LH Jr, Salant DJ. Membranous nephropathy: A journey frombench to bedside. Am J Kidney Dis. 2016;68(1):138-47. doi:10. 1053/j.ajkd.2016.01.030
10. Tomas NM, Beck LH Jr, Meyer-Schwesinger C, Seitz-Polski B, Ma H, Zahner G, et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl JMed. 2014;371(24):2277-87. doi: 10.1056/NEJMoa1409354
11. Wang CH, Su PT, Du XY, Kuo MW, Lin CY, Yang CC, et al. Thrombospondin type I domain containing 7A (THSD7A) mediates endothelial cell migration and tube formation. J Cell Physiol. 2010;222(3): 685-94. doi: 10.1002/jcp.21990
12. Larsen CP, Cossey LN, Beck LH. THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity. Mod Pathol. 2016;29(4):421-6. doi:10.1038/modpathol.2016.32
13. Klouda PT, Manos J, Acheson EJ, Dyer PA, Goldby FS, Harris R, et al. Strong association between idiopathic membranous nephropathy and HLA-DRW3. Lancet. 1979;13;2(8146):770-1.
14. Le Petit JC, Laurent B, Berthoux FC. HLA-DR3 and idiopathic membranous nephritis (IMN) association. Tissue Antigens. 1982;20:227-8. doi: 10.1111/j.1399-0039.1982.tb00350.x
15. Vaughan RW, Demaine AG, Welsh KI. A DQA1 allele is strongly associated with idiopathic membranous nephropathy. Tissue Antigens. 1989;34(5):261-9. doi: 10.1111/j.1399-0039.1989.tb01741.x
16. Ogahara S, Naito S, Abe K, Michinaga I, Arakawa K. Analysis of HLA class II genes in Japanese patients with idiopathic membranous glomerulonephritis. Kidney Int. 1992;41(1):175-82. doi: 10.1038/ki. 1992.24
17. Chevrier D, Giral M, Perrichot R, Latinne D, Coville P, Muller JY, et al. Idiopathic and secondary membranous nephropathy and polymorphism at TAP1 and HLA-DMA loci. Tissue Antigens. 1977;50:164-9. doi: 10.1111/j.1399-0039.1997.tb02855.x
18. Robinson J, Waller MJ, Parham P, Groot N, Bontrop R, Kennedy LJ, et al. IMGT/HLA and IMGT/MHC: sequence databases for the study of the major histocompatibility complex. NucleicAcids Res. 2003;31(1):311-4. doi: 10.1093/nar/gkg070
19.[Khaitov RM, Alexeev LP. HLA gene system and regulation of immune response. Allergiya, Astma i Klinicheskaya Immunologiya. 2000;(8):7-16 (In Russ.)].
20. Horton R, Gibson R, Coggill P, et al. Variation analysis and gene annotation of eight MHC haplotypes: the MHC Haplotype Project. Immunogenetics. 2008;60(1):1-18. doi: 10.1007/s00251-007-0262-2
21. Kiryluk K, Li Y, Scolari F, Sanna-Cherchi S, Choi M, Verbitsky M,
et al. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat Genet. 2014;46(11):1187-96. doi: 10.1038/ng.3118
22. Suranyi MG, Guasch A, Hall B, Myers BD. Elevated levels of tumor necrosis factor- α in the nephrotic syndrome in humans. Am J Kidney Dis. 1993;21:251-9. doi: 10.1016/S0272-6386(12)80742-6
23. Honkanen E, von Willebrand E, Teppo AM, Tornroth T, Gronhagen-Riska C. Adhesion molecules and urinary tumor necrosis factor-α in idiopathic membranous glomerulonephritis. Kidney Int. 1998;53(4): 909-17. doi: 10.1111/j.1523-1755.1998.00833.x
24. Kroeger KM, Carville KS, Abraham LJ. The -308 tumor necrosis factor-α promoter polymorphism effects transcription. Mol Immunol. 1997;34(5):391-9. doi: 10.1016/S0161-5890(97)00052-7
25. Bouma G, Crusius JB, Oudkerk Pool M, Kolkman JJ, von Blom-
berg BM, Kostense PJ, et al. Secretion of tumour necrosis factor-α and lymphotoxin-α in relation to polymorphisms in the TNF genes and HLA-DR alleles. Relevance for inflammatory bowel disease. Scand J Immunol. 1996;43(4):456-63. doi: 10.1046/j.1365-3083.1996.d01-65.x
26. Bantis C, Heering PJ, Aker S, Siekierka M, Kuhr N, Grabensee B, et al. Tumor necrosis factor-alpha gene G-308A polymorphism is a risk factor for the development of membranous glomerulonephritis. Am J Nephrol. 2006;26:12-5. doi: 10.1159/000090706
27. Liu YH, Chen CH, Chen SY, Lin YJ, Liao WL, Tsai CH, et al. Association of phospholipase A2 receptor 1 polymorphisms with idiopathic membranous nephropathy in Chinese patients in Taiwan. J Biomed Sci. 2010;17:81.
28. Kim S, Chin HJ, Na KY, Kim S, Oh J, Chung W, et al. Progressive Renal Disease and Medical Informatics and Genomics Research
(PREMIER) members: Single nucleotide polymorphisms in the phospholipase A2 receptor gene are associated with genetic susceptibility to idiopathic membranous nephropathy. Nephron Clin Pract. 2011; 117(3):c253-8. doi: 10.1159/000320194
29. Stanescu HC, Arcos-Burgos M, Medlar A, Bockenhauer D, Kottgen A, Dragomirescu L, Voinescu C, et al. Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy. N Engl J Med. 2011;364(7):616-26. doi: 10.1056/NEJMoa1009742
30. Strange A, Capon F, Spencer CC, Knight J, Weale ME, Allen MH, et al. Genetic Analysis of Psoriasis Consortium and the Wellcome Trust Case Control Consortium 2. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet. 2010;42(11):985-90. doi: 10.1038/ng.694
31. Smyth DJ, Cooper JD, Howson JM, Walker NM, Plagnol V, Ste-
vens H, et al. PTPN22 Trp620 explains the association of chromosome 1p13 with type 1 diabetes and shows a statistical interaction with HLA class II genotypes. Diabetes. 2008;57(6):1730-7. doi: 10.2337/
db07-1131
32. Lv J, Hou W, Zhou X, Liu G, Zhou F, Zhao N, et al. Interaction between PLA2R1 and HLA-DQA1 variants associates with anti-PLA2R antibodies and membranous nephropathy. J Am Soc Nephrol. 2013;24(8):1323-9. doi: 10.1681/ASN.2012080771
33. Bullich G, Ballarín J, Oliver A, Ayasreh N, Silva I, Santín S, et al. HLA-DQA1 and PLA2R1 polymorphisms and risk of idiopathic membranous nephropathy. Clin J Am Soc Nephrol. 2014;9(2):335-43. doi: 10.2215/CJN.05310513
34. Saeed M, Beggs ML, Walker PD, Larsen CP. PLA2R-associated membranous glomerulopathy is modulated by common variants in PLA2R1 and HLA-DQA1 genes. Genes Immun. 2014 Dec;15(8):556-61. doi: 10.1038/gene.2014.50
35. Sekula P, Li Y, Stanescu HC, Wuttke M, Ekici AB, Bockenhauer D,
et al.; GCKD Investigators. Genetic risk variants for membranous nephropathy: Extension of and association with other chronic kidney disease aetiologies. Nephrol Dial Transplant. 2017;32(2):325-32.
doi: 10.1093/ndt/gfw001
36. Ramachandran R, Kumar V, Kumar A, Yadav AK, Nada R, Kumar H, et al. PLA2R antibodies, glomerular PLA2R deposits and variations in PLA2R1 and HLA-DQA1 genes in primary membranous nephropathy in South Asians. Nephrol Dial Transplant. 2016;31(9):1486-93.
doi: 10.1093/ndt/gfv399
37. Kaga H, Komatsuda A, Omokawa A, Okuyama S, Mori K, Wakui H, Takahashi N. Analysis of PLA2R1 and HLA-DQA1 sequence variants in Japanese patients with idiopathic and secondary membranous nephropathy. Clin Exp Nephrol. 2018 Apr;22(2):275-82. doi: 10.1007/ s10157-017-1471-0
38. Zeng CH, Chen HM, Wang RS, Chen Y, Zhang SH, Liu L, et al. Etiology and clinical characteristics of membranous nephropathy in Chinese patients. Am J Kidney Dis. 2008 Oct;52(4):691-8.
doi: 10.1053/j.ajkd.2008.06.006
39. Hanko JB, Mullan RN, O’Rourke DM, McNamee PT, Maxwell AP, Courtney AE. The changing pattern of adult primary glomerular disease. Nephrol Dial Transplant. 2009 Oct;24(10):3050-4. doi: 10.1093/ ndt/gfp254
40. Coenen MJ, Hofstra JM, Debiec H, Stanescu HC, Medlar AJ, Stengel B, et al. Phospholipase A2 receptor (PLA2R1) sequence variants in idiopathic membranous nephropathy. J Am SocNephrol. 2013;24(4): 677-83. doi: 10.1681/ASN.2012070730
41. 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature. 2015;526(7571):68-74. doi: 10.1038/nature15393
42. Cui Z, Xie LJ, Chen FJ, Pei ZY, Zhang LJ, Qu Z, et al. MHC class II risk alleles and amino acid residues in idiopathic membranous nephropathy. J Am Soc Nephrol. 2017;28(5):1651-64.
doi: 10.1681/ASN. 2016020114
43. Le WB, Shi JS, Zhang T, Liu L, Qin HZ, Liang S, et al. HLA-DRB1*15:01 and HLADRB3*02:02 in PLA2R-related membranous nephropathy. J Am Soc Nephrol. 2017;28(5):1642-50. doi: 10.1681/ ASN.2016060644
44. Kanigicherla D, Gummadova J, McKenzie EA, Roberts SA, Harris S, Nikam M, et al. Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy. Kidney International. 2013;83:940-8. doi: 10.1038/ki.2012.486
ФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
________________________________________________
E.S. Kamyshova, I.N. Bobkova, I.A. Gorelova, P.A. Каkhsurueva, E.E. Filatova
I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia