Экстраренальные формы болезни отложения моноклональных иммуноглобулинов: механизмы, клиническая презентация, диагностика, лечение (обзор литературы)

При моноклональных гаммапатиях клон В-клеточной линии продуцирует моноклональный иммуноглобулин (МИГ), представляющий собой молекулу или одной легкой цепи κ или λ, или одной тяжелой цепи, или полную молекулу иммуноглобулина. В силу аберрантной природы клона и наличия в его генотипе разнообразных мутаций МИГ может оказывать патологическое воздействие на органы и ткани, в том числе аккумулироваться в виде неорганизованных конго-рот негативных гранулярных депозитов. Такой вариант органотоксичности носит название болезни отложения МИГ. Наиболее частая локализация подобных депозитов МИГ – ренальная паренхима. В то же время, подобно AL-амилоидозу, болезнь отложения МИГ может носить системный характер, изолированно поражать разные органы или протекать в виде локальной формы. В настоящем сообщении суммированы текущие представления о механизмах экстраренальной формы болезни отложения МИГ, ее клинических проявлениях, подходах к диагностике и лечению.

1. Multiple myeloma – Aquick reflection on the fast progress / eds by Hajek R. InTech. 2013. 236 p. https://dx.doi.org/10.5772/56515.

2. Del Pozo-Yauner L., Herrera G. A., Perez Carreon J. I. et al. Role of the mechanisms for antibody repertoire diversification in monoclonal light chain deposition disorders: when a friend becomes foe // Front Immunol. 2023. Vol. 14. P. 1203425. https://doi.org/10.3389/fimmu.2023.1203425.

3. Dispenzieri A. Monoclonal gammopathies of clinical significance // Hematology Am Soc Hematol Educ Program. 2020. Vol. 2020, № 1. P. 380–388. https://doi.org/10.1182/hematology.2020000122.

4. Fermand J. P., Bridoux F., Dispenzieri A. et al. Monoclonal gammopathy of clinical significance. P. a novel concept with therapeutic implications // Blood. 2018. Vol. 132, № 14. P. 1478–1485. https://doi.org/10.1182/blood-2018-04-839480.

5. Leung N., Bridoux F., Nasr S. H. Monoclonal gammopathy of renal significance // N Engl J Med. 2021. Vol. 384, № 20. P. 1931–1941. https://doi.org/10.1056/NEJMra1810907.

6. Смирнов А. В., Афанасьев Б. В., Поддубная И. В. и др. Моноклональная гаммапатия ренального значения: консенсус гематологов и нефрологов России по введению нозологии, диагностике и обоснованности клон-ориентированной терапии // Нефрология. 2019. Т. 23, № 6. С. 9–28. https://doi.org/10.36485/1561-6274-2019-236-9-28.

7. Храброва М. С., Добронравов В. А., Смирнов А. В. Поражения почек, ассоциированные с моноклональными гаммапатиями: одноцентровое исследование // Нефрология. 2018. Т. 22, № 6. С. 38–46. https://doi.org/10.24884/1561-6274-2018-22-6-38-46.

8. Cohen C., Joly F., Sibille A. et al. Randall-type monoclonal immunoglobulin deposition disease. P. New insights into the pathogenesis, diagnosis and management // Diagnostics (Basel). 2021. Vol. 11, № 3. P. 420. https://doi.org/10.3390/diagnostics11030420.

9. Herrera G. A., Teng J., Turbat-Herrera E. A. et al. Understanding mesangial pathobiology in AL-Amyloidosis and monoclonal ig light chain deposition disease // Kidney Int Rep. 2020. Vol. 5, № 11. P. 1870–1893. https://doi.org/10.1016/j.ekir.2020.07.013.

10. Joly F., Cohen C., Javaugue V. et al. Randall-type monoclonal immunoglobulin deposition disease: novel insights from a nationwide cohort study // Blood. 2019. Vol. 133, № 6. P. 576–587. https://doi.org/10.1182/blood-2018-09-872028.

11. Pozzi C., Locatelli F. Kidney and liver involvement in monoclonal light chain disorders // Semin Nephrol. 2002. Vol. 22, № 4. P. 319–30.

12. Pozzi C., D’Amico M., Fogazzi G. B. et al. Light chain deposition disease with renal involvement. P. clinical characteristics and prognostic factors // Am J Kidney Dis. 2003. Vol. 42, № 6. P. 1154–63. https://doi.org/10.1053/j.ajkd.2003.08.040.

13. Ikura H., Endo J., Kitakata H. et al. Molecular mechanism of pathogenesis and treatment strategies for AL amyloidosis // Int J Mol Sci. 2022. Vol. 23, № 11. P. 6336. https://doi.org/10.3390/ijms23116336.

14. Weichman K., Dember L. M., Prokaeva T. et al. Clinical and molecular characteristics of patients with non-amyloid light chain deposition disorders, and outcome following treatment with highdose melphalan and autologous stem cell transplantation // Bone Marrow Transplant. 2006. Vol. 38, № 5. P. 339–43. https://doi.org/10.1038/sj.bmt.1705447.

15. Vidal R., Goñi F., Stevens F. et al. Somatic mutations of the L12a gene in V-kappa(1) light chain deposition disease: potential effects on aberrant protein conformation and deposition // Am J Pathol. 1999. Vol. 155, № 6. P. 2009–17. https://doi.org/10.1016/s0002-9440(10)65520-4.

16. Tsushima T., Suzuki T., Terao T. et al. Light chain deposition disease involving kidney and liver in a patient with IgD myeloma // BMC Nephrol. 2021. Vol. 22, № 1. P. 40. https://doi.org/10.1186/s12882-021-02246-9.

17. Nishioka R., Yoshida S., Takamatsu H., Kawano M. Cardiac light-chain deposition disease and hints at diagnosing: a case report // Eur Heart J Case Rep. 2023. Vol. 7, № 2. P. ytad049. https://doi.org/10.1093/ehjcr/ytad049.

18. Palladini G., Dispenzieri A., Gertz M. A. et al. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: P. impact on survival outcomes // J Clin Oncol. 2012. Vol. 30, № 36. P. 4541–9. https://doi.org/10.1200/JCO.2011.37.7614.

19. Said S. M., Best Rocha A., Valeri A. M. et al. The characteristics of patients with kidney light chain deposition disease concurrent with light chain amyloidosis // Kidney Int. 2022. Vol. 101, № 1. P. 152–163. https://doi.org/10.1016/j.kint.2021.10.019.

20. Гудкова А. Я., Лапекин С. В., Бежанишвили Т. Г. и др. AL-амилоидоз с преимущественным поражением сердца. Алгоритм неинвазивной диагностики амилоидной кардиомиопатии // Терапевтический архив. 2021. Т. 93, № 4. C. 487–496. https://doi.org/10.26442/00403660.2021.04.200689.

21. Ramonatxo A., Garcia R., Joly F. et al. Randall-type monoclonal immunoglobulin deposition disease. P. description of cardiac involvement // European Heart Journal. 2020. Vol. 41, № 2. P. ehaa946.2140. https://doi.org/10.1093/ehjci/ehaa946.2140.

22. Buxbaum J. N., Genega E. M., Lazowski P. et al. Infiltrative nonamyloidotic monoclonal immunoglobulin light chain cardiomyopathy: an underappreciated manifestation of plasma cell dyscrasias // Cardiology. 2000. Vol. 93, № 4. P. 220–8. https://doi.org/10.1159/000007030.

23. Mohan M., Buros A., Mathur P. et al. Clinical characteristics and prognostic factors in multiple myeloma patients with light chain deposition disease // Am J Hematol. 2017. Vol. 92, № 8. P. 739–745. https://doi.org/10.1002/ajh.24756.

24. Gandhi M., Pasha S. B., Reznicek E. et al. A case of light chain deposition disease leading to acute liver failure and review of literature // Diseases. 2023. Vol. 11, № 1. P. 24. https://doi.org/10.3390/diseases11010024.

25. Grembiale A., Garlatti E., Ermacora A. et al. An unusual case of cholestatic hepatitis due to light-chain deposition disease // Case Rep Oncol. 2020. Vol. 13, № 3. P. 1343–1348. https://doi.org/10.1159/000509508.

26. Brilland B., Sayegh J., Croue A. et al. Recovery from LCDD-associated Severe Liver Cholestasis: a case report and literature review // J Gastrointestin Liver Dis. 2016. Vol. 25, № 1. P. 99–103. https://doi.org/10.15403/jgld.2014.1121.251.lcd.

27. Gonçalves T. A. P., Donadel C. D., Frezatti R. S. S. et al. Monoclonal gammopathy-associated peripheral neuropathies: Uncovering pearls and challenges // J Peripher Nerv Syst. 2024. Vol. 29, № 2. P. 161‒172. https://doi.org/10.1111/jns.12638.

28. Lunn M. P. Neuropathies and paraproteins // Curr Opin Neurol. 2019. Vol. 32, № 5. P. 658–665. https://doi.org/10.1097/WCO.0000000000000726.

29. Chompoopong P., Mauermann M. L., Siddiqi H., Peltier A. Amyloid neuropathy: From pathophysiology to treatment in light-chain amyloidosis and hereditary transthyretin amyloidosis // Ann Neurol. 2024. Vol. 96, № 3. P. 423–440. https://doi.org/10.1002/ana.26965.

30. Grassi M. P., Clerici F., Perin C. et al. Light chain deposition disease neuropathy resembling amyloid neuropathy in a multiple myeloma patient // Ital J Neurol Sci. 1998. Vol. 19, № 4. P. 229–33. https://doi.org/10.1007/BF02427609.

31. Romano A., Riso V., Bisogni G. et al. Isolated light chain deposition disease neuropathy in a patient with multiple myeloma // Amyloid. 2020. Vol. 27, № 1. P. 67–68. https://doi.org/10.1080/13506129.2019.1669554.

32. Foguem C., Manckoundia P., Pfitzenmeyer P., Dupond J. L. Peripheral neuropathy and VIth nerve palsy related to randall disease successfully treated by high-dose melphalan, autologous blood stem cell transplantation, and VIth nerve decompression surgery // Case Rep Med. 2010. Vol. 2010. P. 542925. https:// doi.org/10.1155/2010/542925.

33. Luigetti M., Frisullo G., Laurenti L. et al. Light chain deposition in peripheral nerve as a cause of mononeuritis multiplex in Waldenström’s macroglobulinaemia // J Neurol Sci. 2010. Vol. 291, № 1–2. P. 89–91. https://doi.org/10.1016/j.jns.2010.01.018.

34. Popović M., Tavćar R., Glavac D. et al. Light chain deposition disease restricted to the brain. P. The first case report // Hum Pathol. 2007. Vol. 38, № 1. P. 179–84. https://doi.org/10.1016/j.humpath.2006.07.010.

35. Mercado J. J., Markert J. M., Meador W. et al. Primary CNS nonamyloidogenic light chain deposition disease: case report and brief review // Int J Surg Pathol. 2017. Vol. 25, № 8. P. 755–760. https://doi.org/10.1177/1066896917717338.

36. Singh A., Okonkwo L., Hoff J. C. et al. Nonamyloid tumoral light-chain-deposition disease (aggregoma) of the paraspinal region // Skeletal Radiol. 2015. Vol. 44, № 12. P. 1839–43. https://doi.org/10.1007/s00256-015-2223-4.

37. Matjašič A., Wechtersbach K., Kavalar R. et al. Brain aggregoma with clonal B-cell perivascular proliferation detected by next-generation sequencing. A case report and review of the literature // Folia Neuropathol. 2021. Vol. 59, № 2. P. 205–211. https://doi.org/10.5114/fn.2021.106405.

38. Skardelly M., Pantazis G., Bisdas S. et al. Primary cerebral lowgrade B-cell lymphoma, monoclonal immunoglobulin deposition disease, cerebral light chain deposition disease and “aggregoma”.P. an update on classification and diagnosis // BMC Neurol. 2013. Vol. 13. P. 107. https://doi.org/10.1186/1471-2377-13-107.

39. Wei C., Wang M., Li J. et al. Light chain deposition disease presenting with gastrointestinal disorder as primary manifestation: report of two cases and literature review // J Int Med Res. 2024. Vol. 52, № 3. P. 3000605241233972. https://doi.org/10.1177/03000605241233972.

40. Lestelle F., Beigelman C., Rotzinger D. et al. Phenotypes and outcome of diff pulmonary non-amyloid light chain deposition disease // Respir Res. 2024. Vol. 25, № 1. P. 159. https://doi.org/10.1186/s12931-024-02798-y.

41. Baqir M., Moua T., White D. et al. Pulmonary nodular and cystic light chain deposition disease. P. A retrospective review of 10 cases // Respir Med. 2020. Vol. 164. P. 105896. https://doi.org/10.1016/j.rmed.2020.105896.

42. Khoor A., Myers J. L., Tazelaar H. D., Kurtin P. J. Amyloid-like pulmonary nodules, including localized light-chain deposition: clinicopathologic analysis of three cases //Am J Clin Pathol. 2004. Vol. 121,№ 2. P. 200–4. https://doi.org/10.1309/3GEC-PW24-02F6-V8EK.

43. Bhargava P., Rushin J. M., Rusnock E. J. et al. Pulmonary light chain deposition disease: report of five cases and review of the literature // Am J Surg Pathol. 2007. Vol. 31, № 2. P. 267–76. https://doi.org/10.1097/01.pas.0000213358.18380.d2.

44. Colombat M., Holifanjaniaina S., Guillonneau F. et al. Mass spectrometry-based proteomic analysis: a good diagnostic tool for cystic lung light chain deposition disease //Am J Respir Crit Care Med. 2013. Vol. 188, № 3. P. 404–5. https://doi.org/10.1164/rccm.201301-0071LE.

45. Colombat M., Mal H., Copie-Bergman C. et al. Primary cystic lung light chain deposition disease: a clinicopathologic entity derived from unmutated B cells with a stereotyped IGHV4-34/ IGKV1 receptor // Blood. 2008. Vol. 112, № 5. P. 2004–12. https://doi.org/10.1182/blood-2007-11-123596.

46. Rajapreyar I., Joly J., Tallaj J. et al. Pulmonary vascular disease due to plasma cell dyscrasia // Mayo Clin Proc Innov Qual Outcomes. 2020. Vol. 5, № 1. P. 210–218. https://doi.org/10.1016/j.mayocpiqo.2020.09.004.

47. Claveau J. S., Wetter D. A., Kumar S. Cutaneous manifestations of monoclonal gammopathy // Blood Cancer J. 2022. Vol. 12, № 4. P. 58. https://doi.org/10.1038/s41408-022-00661-1.

48. Alegría-Landa V., Cerroni L., Kutzner H., Requena L. Paraprotein deposits in the skin // J Am Acad Dermatol. 2017. Vol. 77, № 6. P. 1145–1158. https://doi.org/10.1016/j.jaad.2017.07.039.

49. Topalidis C., Boulogeorgou K., Lazaridis A., Koletsa T. Light chain deposition disease: Spotlight on a rare cutaneous disease // Eur J Dermatol. 2023. Vol. 33, № 3. P. 297–299. https://doi.org/10.1684/ejd.2023.4486.

50. Safa G., Dhib M., Soubrane J. C. et al. Maladie des dépôts de chaînes lourdes et légères avec manifestations cutanées et rénales [Light and heavy chain deposition disease with cutaneous and renal manifestations] // Ann Dermatol Venereol. 1996. Vol. 123, № 8. P. 490–2. (In French).

51. Hendricks C., Fernández Figueras M. T., Liersch J. et al. Cutaneous light chain deposition disease: A report of 2 cases and review of the literature // Am J Dermatopathol. 2018. Vol. 40, № 5. P. 337–341. https://doi.org/10.1097/DAD.000000000000099.

52. O’Malley J. T., D’Agati V. D., Sherman W. H., Grossman M. E. Acquired cutis laxa associated with heavy chain deposition disease involving dermal elastic fi // JAMA Dermatol. 2014. Vol. 150, № 11. P. 1192–6. https://doi.org/10.1001/jamadermatol.2014.725.

53. Dima D., Jiang D., Singh D. J. et al. Multiple myeloma therapy: Emerging trends and challenges // Cancers (Basel). 2022. Vol. 14, № 17. P. 4082. https://doi.org/10.3390/cancers14174082.

54. Aimo A., Vergaro G., Pucci A. et al. Cardiac light-chain deposition disease relapsing in the transplanted heart // Amyloid. 2017. Vol. 24, № 2. P. 135–137. https://doi.org/10.1080/13506129.2017.1334196.