nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.36485/1561-6274-2022-26-3-95-101nefr-2145Research ArticleНАБЛЮДЕНИЯ ИЗ ПРАКТИКИPRACTICAL NOTESСлучай первичной мембранозной нефропатии в сочетании с поражением мышц и периферических нервовCase report of primary membranous nephropathy associated with muscle and peripheral nerve damagehttps://orcid.org/0000-0001-8433-876XКочоянЗ. Ш.KochoyanZ. Sh.

Зинаида Шакроевна Кочоян

кафедра пропедевтики внутренних болезней с клиникой

197022

ул. Л. Толстого, д. 17, корп. 54

Санкт-Петербург

тел.: +7(812)338-69-22

Zinaida Sh. Kochoyan, clinical resident

Department of Propedeutics of Internal Diseases with the Clinic

197022

L. Tolstoy st., 17, build. 54

Saint Petersburg

Phone: +7(812)338-69-22

zinshak@gmail.comhttps://orcid.org/0000-0001-6527-6962БыстроваО. Б.BystrovaO. B.

Ольга Борисовна Быстрова, врач-нефролог

Научно-исследовательский институт нефрологии

нефрологическое отделение № 2

197022

ул. Л. Толстого, д. 17, корп. 54

Санкт-Петербург

тел.: +7(812)338-69-22

Olga B. Bystrova, nephrologist

Research Institute of Nephrology

2nd Nephrology Unit

197022

L. Tolstoy st., 17, build. 54

Saint Petersburg

Phone: +7(812)338-69-22

bystr.ol@mail.ruhttps://orcid.org/0000-0002-7179-5520ДобронравовВ. А.DobronravovV. A.

Владимир Александрович Добронравов, проф., д-р мед. наук, директор научно-исследовательского института, профессор кафедры

Научно-исследовательский институт нефрологии

кафедра пропедевтики внутренних болезней с клиникой

197022

ул. Л. Толстого, д. 17, корп. 54

Санкт-Петербург

тел.: +7(812)338-69-01

Vladimir A. Dobronravov, Prof., MD, PhD, DSc, , Director, professor of the department

Department of Propedeutics of Internal Diseases with the Clinic

Research Institute of Nephrology

197022

L. Tolstoy st., 17, build. 54

Saint Petersburg

Phone: +7(812)338-69-01

dobronravov@nephrolog.ruПервый Санкт-Петербургский государственный медицинский университет им. акад. И. П. ПавловаРоссияPavlov UniversityRussian Federation20221109202226395101Copyright © Кочоян З.Ш., Быстрова О.Б., Добронравов В.А., 20222022Кочоян З.Ш., Быстрова О.Б., Добронравов В.А.Kochoyan Z.S., Bystrova O.B., Dobronravov V.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/2145

   Первичная мембранозная нефропатия (ПМН) – типичная причина развития нефротического синдрома у взрослых. Ключевым моментом патогенеза болезни является образование иммуноглобулинов класса G 4 типа (IgG4) к подоцитарному трансмембранному рецептору секретируемой фосфолипазы A2 M-типа (anti-PLA2R) с последующим формированием субэпителиальных депозитов иммунных комплексов (ИК) in situ. Представленный нами случай молодого мужчины, 37 лет, с ПМН в сочетании с демиелинизирующей полинейропатией и идиопатическим воспалительным поражением скелетной мускулатуры демонстрирует возможный вариант экстраренальных эффектов IgG4-anti-PLA2R с обсуждением дифференциальной диагностики и вероятных механизмов дисбаланса секретируемых и внутриклеточных фосфолипаз.

   Primary membranous nephropathy (PMN) typical cause of nephrotic syndrome in adults. The key point in its pathogenesis is the production of IgG4 subclass autoantibodies (IgG4) against podocytic transmembrane phospholipase A2 M-type receptor (anti-PLA2R), followed by the deposition of subepithelial immune complexes (IC) in situ. We present a case of a 37-year-old young man with PMN associated with demyelinating polyneuropathy and idiopathic inflammatory lesions of skeletal muscles demonstrating a possible variant of extrarenal effects of IgG4-anti-PLA2R with an extended analysis of diagnostics and probable mechanisms of imbalance of secreted and intracellular phospholipases.

первичная мембранозная нефропатияантитела к рецептору фосфолипазы А2 М-типасекретируемые фосфолипазы А2демиелинизирующая полинейропатиямиолизprimary membranous nephropathyanti-PLA2R antibodiessecreted phospholipases A2demyelinating polyneuropathymyolysisReferencesGlassock R. J. The pathogenesis of idiopathic membranous nephropathy: a 50-year odyssey. Am J Kidney Dis 2010; 56 (1): 157–167. doi: 10.1053/j.ajkd.2010.01.008.Glassock R. J. The pathogenesis of idiopathic membranous nephropathy: a 50-year odyssey. Am J Kidney Dis 2010; 56 (1): 157–167. doi: 10.1053/j.ajkd.2010.01.008.Beck L. H. Jr., Bonegio R. G., Lambeau G. 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/NEJMoa0810457Beck L. H. Jr., Bonegio R. G., Lambeau G. 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/NEJMoa0810457Schlumberger W., Hornig N., Lange S. et al. Differential diagnosis of membranous nephropathy with autoantibodies to phospholipase A2 receptor 1. Autoimmun Rev 2014; 13 (2): 108–113. doi:10.1038/srep08803Schlumberger W., Hornig N., Lange S. et al. Differential diagnosis of membranous nephropathy with autoantibodies to phospholipase A2 receptor 1. Autoimmun Rev 2014; 13 (2): 108–113. doi:10.1038/srep08803Ma H., Sandor D. G., Beck L. H. Jr. The role of complement in membranous nephropathy. Seminars in Nephrology 2013; 33 (6): 531–542. doi:10.1016/j.semnephrol.2013.08.004Ma H., Sandor D. G., Beck L. H. Jr. The role of complement in membranous nephropathy. Seminars in Nephrology 2013; 33 (6): 531–542. doi:10.1016/j.semnephrol.2013.08.004Yang Y., Wang Ch. Liping J. et al. IgG4 anti-phospholipase A2 receptor might activate lectin and alternative complement pathway meanwhile in idiopathic membranous nephropathy: an inspiration from a cross-sectional study. Immunol Res 2016; 64 (4): 919–930. doi: 10.1007/s12026-016-8790-1Yang Y., Wang Ch. Liping J. et al. IgG4 anti-phospholipase A2 receptor might activate lectin and alternative complement pathway meanwhile in idiopathic membranous nephropathy: an inspiration from a cross-sectional study. Immunol Res 2016; 64 (4): 919–930. doi: 10.1007/s12026-016-8790-1Passerini P., Ponticelli C. Membranous nephropathy. In: Ponticelli C., Glassock R. (eds). Treatment of Primary Glomerulonephritis, 2nd ed. Oxford University Press: Oxford, UK, 2009:261–312. doi:10.1093/med/9780199552887.001.0001Passerini P., Ponticelli C. Membranous nephropathy. In: Ponticelli C., Glassock R. (eds). Treatment of Primary Glomerulonephritis, 2nd ed. Oxford University Press: Oxford, UK, 2009:261–312. doi:10.1093/med/9780199552887.001.0001Добронравов В. А. Новый подход к быстрой индукции ремиссии у больных при мембранозной нефропатии / В. А. Добронравов [и др.] // Терапевтический архив. – 2021. – 93 (6): 706–712. doi: 10.26442/00403660.2021.06.200865 / Dobronravov V. A., Bystrova O. B., Kochoyan Z. Sh., Fomicheva E. N. A novel approach to rapid induction of remission in primary membranous nephropathy. Ter arkh 2021; 93 (6): 706-712. (In Russ) doi:10.26442/00403660.2021.06.200865Добронравов В. А. Новый подход к быстрой индукции ремиссии у больных при мембранозной нефропатии / В. А. Добронравов [и др.] // Терапевтический архив. – 2021. – 93 (6): 706–712. doi: 10.26442/00403660.2021.06.200865 / Dobronravov V. A., Bystrova O. B., Kochoyan Z. Sh., Fomicheva E. N. A novel approach to rapid induction of remission in primary membranous nephropathy. Ter arkh 2021; 93 (6): 706-712. (In Russ) doi:10.26442/00403660.2021.06.200865Omerhoca S., Akkas S. A., Icen N. K. Multiple sclerosis: diagnosis and differential diagnosis. Noro Psikiyatr Ars 2018; 55 (1): 1–9. doi: 10.29399/npa.23418Omerhoca S., Akkas S. A., Icen N. K. Multiple sclerosis: diagnosis and differential diagnosis. Noro Psikiyatr Ars 2018; 55 (1): 1–9. doi: 10.29399/npa.23418Van den Bergh P. Y., Hadden R. D., Bouche P. et al. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society – first revision. Eur J Neurol 2010; 17 (1): 356–363. doi:10.1111/j.1468-1331.2009.02930.xVan den Bergh P. Y., Hadden R. D., Bouche P. et al. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society – first revision. Eur J Neurol 2010; 17 (1): 356–363. doi:10.1111/j.1468-1331.2009.02930.xBohan A., Peter J. B. Polymyositis and dermatomyositis (first of two parts). N Engl J Med 1975; 292 (7): 344–347. doi: 10.1056/NEJM197502132920706Bohan A., Peter J. B. Polymyositis and dermatomyositis (first of two parts). N Engl J Med 1975; 292 (7): 344–347. doi: 10.1056/NEJM197502132920706Bohan A., Peter J. B. Polymyositis and dermatomyositis (second of two parts). N Engl J Med 1975; 292 (8): 403–407. doi: 10.1056/NEJM197502202920807Bohan A., Peter J. B. Polymyositis and dermatomyositis (second of two parts). N Engl J Med 1975; 292 (8): 403–407. doi: 10.1056/NEJM197502202920807Kohli A., Tandon P., Kher V. Chronic inflammatory demyelinating polyradiculoneuropathy with membranous glomerulonephritis: report of one case. Clin Neurol Neurosurg 1992; 94 (1): 31–33. doi: 10.1016/0303-8467(92)90115-jKohli A., Tandon P., Kher V. Chronic inflammatory demyelinating polyradiculoneuropathy with membranous glomerulonephritis: report of one case. Clin Neurol Neurosurg 1992; 94 (1): 31–33. doi: 10.1016/0303-8467(92)90115-jMobbs R. J., Tuck R. R., Hurley B. Chronic inflammatory demyelinating polyneuropathy associated with membranous glomerulonephritis: case report. J Clin Neurosci 2000; 7 (5): 454–455. doi: 10.1054/jocn.1999.0235Mobbs R. J., Tuck R. R., Hurley B. Chronic inflammatory demyelinating polyneuropathy associated with membranous glomerulonephritis: case report. J Clin Neurosci 2000; 7 (5): 454–455. doi: 10.1054/jocn.1999.0235Wong A. H. Y., Kokubun N., Fukami Y. et al. Chronic inflammatory demyelinating polyneuropathy with membranous nephropathy. J Peripher Nerv Syst 2015; 20 (1): 63–66. doi: 10.1111/jns.12113Wong A. H. Y., Kokubun N., Fukami Y. et al. Chronic inflammatory demyelinating polyneuropathy with membranous nephropathy. J Peripher Nerv Syst 2015; 20 (1): 63–66. doi: 10.1111/jns.12113Режим доступа: https://www.genecards.org/cgi-bin/carddisp.pl? gene=PLA2R1 [Available at: https://www.genecards.org/cgi-bin/carddisp.pl?gene=PLA2R1]Режим доступа: https://www.genecards.org/cgi-bin/carddisp.pl? gene=PLA2R1 [Available at: https://www.genecards.org/cgi-bin/carddisp.pl?gene=PLA2R1]Режим доступа: https://www.ncbi.nlm.nih.gov/gene/22925 [Available at: https://www.ncbi.nlm.nih.gov/gene/22925]Режим доступа: https://www.ncbi.nlm.nih.gov/gene/22925 [Available at: https://www.ncbi.nlm.nih.gov/gene/22925]Hanasaki K., Arita H. Phospholipase A2 receptor: a regulator of biological functions of secretory phospholipase A2. Prostaglandins Other Lipid Mediat 2002; 68–69: 71–82. doi: 10.1016/s0090-6980(02)00022-9Hanasaki K., Arita H. Phospholipase A2 receptor: a regulator of biological functions of secretory phospholipase A2. Prostaglandins Other Lipid Mediat 2002; 68–69: 71–82. doi: 10.1016/s0090-6980(02)00022-9Liu W., Gao Ch., Dai H. et al. Immunological pathogenesis of membranous nephropathy: focus on PLA2R1 and its role. Front Immunol 2019; 10: 1809. doi:10.3389/fimmu.2019.01809Liu W., Gao Ch., Dai H. et al. Immunological pathogenesis of membranous nephropathy: focus on PLA2R1 and its role. Front Immunol 2019; 10: 1809. doi:10.3389/fimmu.2019.01809Dennis E. A., Cao J., Hsu Y. H. et al. Phospholipase A2 Enzymes: Physical structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention. Chem Rev 2011; 111 (10): 6130–6185. doi:10.1021/cr200085wDennis E. A., Cao J., Hsu Y. H. et al. Phospholipase A2 Enzymes: Physical structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention. Chem Rev 2011; 111 (10): 6130–6185. doi:10.1021/cr200085wQuach N. D., Arnold R. D., Cummings B. S. Secretory Phospholipase A2 enzymes as pharmacological targets for treatment of disease. Biochem Pharmacol 2014; 90 (4): 338–348. doi:10.1016/j.bcp.2014.05.022Quach N. D., Arnold R. D., Cummings B. S. Secretory Phospholipase A2 enzymes as pharmacological targets for treatment of disease. Biochem Pharmacol 2014; 90 (4): 338–348. doi:10.1016/j.bcp.2014.05.022Sribar J., Krizaj I. Secreted phospholipids a2 – not just enzymes. Acta Chem Slovn 2011; 58 (4): 678–688. PMID: 24061115Sribar J., Krizaj I. Secreted phospholipids a2 – not just enzymes. Acta Chem Slovn 2011; 58 (4): 678–688. PMID: 24061115Murakami M. Lypoquality control by Phospholipase A2 enzymes. Proc Jpn Acad Ser B Phys Biol Sci 2017; 93 (9): 677–702. doi: 10.2183/pjab.93.043Murakami M. Lypoquality control by Phospholipase A2 enzymes. Proc Jpn Acad Ser B Phys Biol Sci 2017; 93 (9): 677–702. doi: 10.2183/pjab.93.043Galluzzi L., Kepp O., Krautwald S. et al. Molecular mechanisms of regulated necrosis. Semin Cell Dev Biol 2014; 35: 24–32. doi:10.1016/j.semcdb.2014.02.006Galluzzi L., Kepp O., Krautwald S. et al. Molecular mechanisms of regulated necrosis. Semin Cell Dev Biol 2014; 35: 24–32. doi:10.1016/j.semcdb.2014.02.006Augert A., Payre C., Launoit Y. et al. The M-type Receptor PLA2R Regulates Senescence Through the p53 Pathway. EMBO Rep 2009; 10 (3): 271–277. doi:10.1038/embor.2008.255Augert A., Payre C., Launoit Y. et al. The M-type Receptor PLA2R Regulates Senescence Through the p53 Pathway. EMBO Rep 2009; 10 (3): 271–277. doi:10.1038/embor.2008.255Pan Y., Wan J., Liu Y. et al. sPLA2 IB induces human podocyte apoptosis via the M-type Phospholipase A2 receptor. Sci Rep 2014; 4: 6660:1–11. doi:10.1038/srep06660Pan Y., Wan J., Liu Y. et al. sPLA2 IB induces human podocyte apoptosis via the M-type Phospholipase A2 receptor. Sci Rep 2014; 4: 6660:1–11. doi:10.1038/srep06660Yagami T., Ueda K., Asakura K. et al. Group IB secretory Phospholipase A2 induces neuronal cell death via apoptosis. J Neurochem 2002; 81 (3): 449–461. doi:10.1046/j.1471-4159.2002.00800.xYagami T., Ueda K., Asakura K. et al. Group IB secretory Phospholipase A2 induces neuronal cell death via apoptosis. J Neurochem 2002; 81 (3): 449–461. doi:10.1046/j.1471-4159.2002.00800.xTappia P., Singal T., Dent M. et al. Phospholipid-mediated signaling in diseased myocardium. Future Lipidol 2006; 1 (6): 701–717. doi:10.2217/17460875.1.6.701Tappia P., Singal T., Dent M. et al. Phospholipid-mediated signaling in diseased myocardium. Future Lipidol 2006; 1 (6): 701–717. doi:10.2217/17460875.1.6.701Huijbers M. G., Querol L. A., Niks E. H. et al. The expanding field of IgG4-mediated neurological autoimmune disorders. Eur J Neurol 2015; 22 (8): 1151–1161. doi:10.1111/ene.12758Huijbers M. G., Querol L. A., Niks E. H. et al. The expanding field of IgG4-mediated neurological autoimmune disorders. Eur J Neurol 2015; 22 (8): 1151–1161. doi:10.1111/ene.12758Querol L., Devaux J., Rojas-Garcia R. et al. Autoantibodies in chronic inflammatory neuropathies: diagnostic and therapeutic implications. Nat Rev Neurol 2017; 13 (9): 533–547. doi: 10.1038/nrneurol.2017.84Querol L., Devaux J., Rojas-Garcia R. et al. Autoantibodies in chronic inflammatory neuropathies: diagnostic and therapeutic implications. Nat Rev Neurol 2017; 13 (9): 533–547. doi: 10.1038/nrneurol.2017.84Koneczny I. A new classification system for IgG4 Autoantibodies. Front Immunol 2018; 9: 97. doi: 10.3389/fimmu.2018.00097Koneczny I. A new classification system for IgG4 Autoantibodies. Front Immunol 2018; 9: 97. doi: 10.3389/fimmu.2018.00097Umehara H., Nakajima A., Nakamura T. et al. IgG4-related disease and its pathogenesis-cross-talk between innate and acquired immunity. Int Immunol 2014; 26 (11): 585–595. doi: 10.1093/intimm/dxu074Umehara H., Nakajima A., Nakamura T. et al. IgG4-related disease and its pathogenesis-cross-talk between innate and acquired immunity. Int Immunol 2014; 26 (11): 585–595. doi: 10.1093/intimm/dxu074Ronco P., Debiec H. Anti-phospholipase A2 receptor antibodies and the pathogenesis of membranous nephropathy. Nephron Clin Pract 2014; 128 (3–4): 232–237. doi: 10.1159/000368588Ronco P., Debiec H. Anti-phospholipase A2 receptor antibodies and the pathogenesis of membranous nephropathy. Nephron Clin Pract 2014; 128 (3–4): 232–237. doi: 10.1159/000368588

The authors declare that there are no conflicts of interest present.