Современные подходы к выявлению моноклональной гаммапатии неопределенного значения (MGUS) у больных с поражением почек
Современные подходы к выявлению моноклональной гаммапатии неопределенного значения (MGUS) у больных с поражением почек
Козловская (Лысенко) Л.В., Чеботарева Н.В., Мрыхин Н.Н. и др. Современные подходы к выявлению моноклональной гаммапатии неопределенного значения (MGUS) у больных с поражением почек. Терапевтический архив. 2019; 91 (6): 67–72. DOI: 10.26442/00403660.2019.06.000281
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Аннотация
Моноклональная гаммапатия (МГ) неопределенного значения (MGUS) является не только предопухолевым состоянием, предшествующим развитию множественной миеломы (ММ) и других секретирующих опухолей, но и возможной причиной заболеваний неопухолевой природы, в том числе поражения почек
Цель исследования. Оценить информативность методов «Freelite», в добавление к электрофорезу (ЭФ) и иммунофиксации (ИФ) белков сыворотки и мочи, для выявления МГ у больных с поражением почек.
Материалы и методы. Из 113 больных с МГ было отобрано 87 больных с поражением почек, у которых МГ установлена при использовании метода ЭФ белков сыворотки, ИФ и метода определения свободных легких цепей – FLC «Freelite». Проведена оценка эффективности в диагностике МГ этой трехкомпонентной сывороточной панели.
Результаты и обсуждение. Из 87 больных с поражением почек МГ была определена у 39 (45%) пациентов с AL-амилоидозом, 16 (18%) – с (HCV+) криоглобулинемическим гломерулонефритом (крио-ГН), 28 (32%) – с хроническим ГН (ХГН), 4 (4%) – с болезнью отложения легких цепей (БОЛЦ) с помощью трехкомпонентной скрининговой панели. Определение МГ с помощью ЭФ было возможным только у 38 (44%) больных. Добавление к сывороточным электрофоретическим методам вместо метода «Freelite» ЭФ и ИФ мочи уменьшило число пропущенных больных с моноклональной гаммапатией – в целом с 24 (27%) до 11 (13%), но не достигло чувствительности трехкомпонентной сывороточной скрининговой панели. У 10 (11,5%) пациентов МГ была представлена только интактными mIg с одним типом легких цепей – либо κ, либо λ. Наиболее часто – у 25% больных – интактная МГ наблюдалась при HCV(+) крио-ГН. У 37 (42,5%) пациентов выявлена комбинация интактных mIgM, mIgG или mIgA с mFLC. Почти у половины (46%) больных обнаружены только mFLC – анормальное отношение κ/λ.
Заключение. Трехкомпонентная сывороточная скрининговая панель ЭФ+ИФ+«Freelite» расширяет возможности распознавания МГ малого объема (MGUS) и должна быть введена в алгоритм обследования больных нефрологического профиля.
Ключевые слова: моноклональная гаммапатия, метод иммунофиксации, Freelite, амилоидоз, хронический гломерулонефрит.
Aim. To assess the diagnostic value of “Freelite” methods in addition to electrophoresis (EF) and immunofixation (IF) of serum and urine proteins for detecting MG in patients with kidney diseases.
Materials and methods. 87 patients with kidney damage, in which MG was established using the method of electrophoresis of serum proteins (EF), immunofixation (IF) and the method of free light chains determination – FLC “Freelite” were selected. The diagnostic value of three-component serum panel was compared with EF and IF.
Results and discussion. AL-amyloidosis with kidney involvement was diagnosed in 41% patients, cryoglobulinemic glomerulonephritis (cryo GN) – in 18%, chronic glomerulonephritis (CGN) – in 35%, also there was small number of patients with light chain disease and cast-nephropathy. Determination of MG using EP was possible only in 38 (44%). Adding to the serum electrophoretic methods instead of the “Freelite” method, the urine EF and IF reduced the number of missed patients with monoclonal gammopathy from 24 (27%) to 11 (13%), including in the subgroup of patients with AL-amyloidosis but did not reach the sensitivity of the three-component serum screening panel. In 10 (11.5%) MG was represented only by intact mIg with one type of light chain, either κ or λ. Most often – in 25% of patients, intact monoclonal gammopathy was observed in HCV (+) cryo GN. A combination of intact mIgM, mIgG or mIgA with mFLC, was detected in 37 (42.5%). In almost half (46%) of the patients, only mFLC was detected – an abnormal κ/λ ratio.
Conclusion: The serum screening panel EF + IF + “Freelite” spreads the low-grade monoclonal gammopathy recognition (MGUS) and should be included in the algorithm of examining patients with kidney disease.
Keywords: monoclonal gammopathy, immunofixation of proteins, “Freelite”, amyloidosis, chronic glomerulonephritis.
Цель исследования. Оценить информативность методов «Freelite», в добавление к электрофорезу (ЭФ) и иммунофиксации (ИФ) белков сыворотки и мочи, для выявления МГ у больных с поражением почек.
Материалы и методы. Из 113 больных с МГ было отобрано 87 больных с поражением почек, у которых МГ установлена при использовании метода ЭФ белков сыворотки, ИФ и метода определения свободных легких цепей – FLC «Freelite». Проведена оценка эффективности в диагностике МГ этой трехкомпонентной сывороточной панели.
Результаты и обсуждение. Из 87 больных с поражением почек МГ была определена у 39 (45%) пациентов с AL-амилоидозом, 16 (18%) – с (HCV+) криоглобулинемическим гломерулонефритом (крио-ГН), 28 (32%) – с хроническим ГН (ХГН), 4 (4%) – с болезнью отложения легких цепей (БОЛЦ) с помощью трехкомпонентной скрининговой панели. Определение МГ с помощью ЭФ было возможным только у 38 (44%) больных. Добавление к сывороточным электрофоретическим методам вместо метода «Freelite» ЭФ и ИФ мочи уменьшило число пропущенных больных с моноклональной гаммапатией – в целом с 24 (27%) до 11 (13%), но не достигло чувствительности трехкомпонентной сывороточной скрининговой панели. У 10 (11,5%) пациентов МГ была представлена только интактными mIg с одним типом легких цепей – либо κ, либо λ. Наиболее часто – у 25% больных – интактная МГ наблюдалась при HCV(+) крио-ГН. У 37 (42,5%) пациентов выявлена комбинация интактных mIgM, mIgG или mIgA с mFLC. Почти у половины (46%) больных обнаружены только mFLC – анормальное отношение κ/λ.
Заключение. Трехкомпонентная сывороточная скрининговая панель ЭФ+ИФ+«Freelite» расширяет возможности распознавания МГ малого объема (MGUS) и должна быть введена в алгоритм обследования больных нефрологического профиля.
Ключевые слова: моноклональная гаммапатия, метод иммунофиксации, Freelite, амилоидоз, хронический гломерулонефрит.
________________________________________________
Aim. To assess the diagnostic value of “Freelite” methods in addition to electrophoresis (EF) and immunofixation (IF) of serum and urine proteins for detecting MG in patients with kidney diseases.
Materials and methods. 87 patients with kidney damage, in which MG was established using the method of electrophoresis of serum proteins (EF), immunofixation (IF) and the method of free light chains determination – FLC “Freelite” were selected. The diagnostic value of three-component serum panel was compared with EF and IF.
Results and discussion. AL-amyloidosis with kidney involvement was diagnosed in 41% patients, cryoglobulinemic glomerulonephritis (cryo GN) – in 18%, chronic glomerulonephritis (CGN) – in 35%, also there was small number of patients with light chain disease and cast-nephropathy. Determination of MG using EP was possible only in 38 (44%). Adding to the serum electrophoretic methods instead of the “Freelite” method, the urine EF and IF reduced the number of missed patients with monoclonal gammopathy from 24 (27%) to 11 (13%), including in the subgroup of patients with AL-amyloidosis but did not reach the sensitivity of the three-component serum screening panel. In 10 (11.5%) MG was represented only by intact mIg with one type of light chain, either κ or λ. Most often – in 25% of patients, intact monoclonal gammopathy was observed in HCV (+) cryo GN. A combination of intact mIgM, mIgG or mIgA with mFLC, was detected in 37 (42.5%). In almost half (46%) of the patients, only mFLC was detected – an abnormal κ/λ ratio.
Conclusion: The serum screening panel EF + IF + “Freelite” spreads the low-grade monoclonal gammopathy recognition (MGUS) and should be included in the algorithm of examining patients with kidney disease.
Keywords: monoclonal gammopathy, immunofixation of proteins, “Freelite”, amyloidosis, chronic glomerulonephritis.
Список литературы
1. Leung N, Bridoux F, Hutchison CA, Nasr SH, Cockwell P, Fermand JP, Dispenzieri A, Song KW, Kyle RA; International Kidney and Monoclonal Gammopathy Research Group. Monoclonal gammopathy of renal significance: when MGUS is no longer undetermined or insignificant. Blood. 2012;120(22):4292-5. doi: 10.1182/ blood-2012-07-445304
2. Parry H, Pratt G, Hutchison C. Monoclonal gammopathy of undetermined significance: an update for nephrologists. Adv Chron Kidney Dis. 2012;19(5):291-6. doi: 10.1053/j.ackd.2012.07.006
3. Nasr SH, Satoskar A, Markowitz GS, Valeri AM, Appel GB, Stokes MB, Nadasdy T, D'Agati VD. Proliferative glomerulonephritis with monoclonal IgG deposits. J Am Soc Nephrol. 2009;20:2055-64. doi: 10.1681/ASN.2009010110
4. Bridoux F, Leung N, Hutchison CA, Touchard G, Sethi S, Fermand JP, Picken MM, Herrera GA, Kastritis E, Merlini G, Roussel M, Fervenza FC, Dispenzieri A, Kyle RA, Nasr SH; International Kidney and Monoclonal Gammopathy Research Group. Diagnosis of monoclonal gammopathy of renal significance. Kidney Int. 2015;87(4):698-711. doi: 10.1038/ki.2014.408
5. Hogan JJ, Weiss BM. Bridging the divide: an onco-nephrologic approach to the monoclonal gammopathies of renal significance. Clin J Am Soc Nephrol. 2016;11(9):1681-91. doi: 10.2215/CJN.03160316
6. Chauvet S, Frémeaux-Bacchi V, Petitprez F, Karras A, Daniel L, Burtey S, Choukroun G, Delmas Y, Guerrot D, François A, Le Quintrec M, Javaugue V, Ribes D, Vrigneaud L, Arnulf B, Goujon JM, Ronco P, Touchard G, Bridoux F. Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy-associated C3 glomerulopathy. Blood. 2017;129(11):1437-47. doi: 10.1182/blood-2016-08-737163
7. Willrich MAV, Murray DL, Kyle RA. Laboratory testing for monoclonal gammopathies: Focus on monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Clin Biochem. 2018;51:38-47. doi: 10.1016/j.clinbiochem.2017.05.001
8. Katzmann JA, Kyle RA, Benson J, Larson DR, Snyder MR, Lust JA, Rajkumar SV, Dispenzieri A. Screening panels for detection of monoclonal gammopathies. Clin Chem. 2009;55(8):1517-22. doi: 10.1373/clinchem.2009.126664
9. Dispenzieri A, Kyle R, Merlini G, Miguel JS, Ludwig H, Hajek R, Palumbo A, Jagannath S, Blade J, Lonial S, Dimopoulos M, Comenzo R, Einsele H, Barlogie B, Anderson K, Gertz M, Harousseau JL, Attal M, Tosi P, Sonneveld P, Boccadoro M, Morgan G, Richardson P, Sezer O, Mateos MV, Cavo M, Joshua D, Turesson I, Chen W, Shimizu K, Powles R, Rajkumar SV, Durie BG; International Myeloma Working Group. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 209;23:215-24. doi: 10.1038/leu.2008.307
10. Dimopoulos M, Kyle R, Fermand JP, Rajkumar SV, San Miguel J, Chanan-Khan A, Ludwig H, Joshua D, Mehta J, Gertz M, Avet-Loiseau H, Beksaç M, Anderson KC, Moreau P, Singhal S, Goldschmidt H, Boccadoro M, Kumar S, Giralt S, Munshi NC, Jagannath S; International Myeloma Workshop Consensus Panel 3. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood. 2011;117(18):4701-5. doi: 10.1182/blood-2010-10-299529
11. Hill PG, Forsyth JM, Rai B, Mayne S. Serum free light chains: an alternative test to urine Bence Jones proteins when screening for monoclonal gammopathies. Clin Chem. 2006;52:1743-8. doi: 10.1373/clinchem.2006.069104
12. Jenner E. Serum free light chains in clinical laboratory diagnostics. Clin Chim Acta. 2014;427:15-20. doi: 10.1016/j.cca.2013.08.018
13. Palladini G, Russo P, Bosoni T, Verga L, Sarais G, Lavatelli F, Nuvolone M, Obici L, Casarini S, Donadei S, Albertini R, Righetti G, Marini M, Graziani MS, Melzi D'Eril GV, Moratti R, Merlini G. Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem. 2009;55(3):499-504. doi: 10.1373/clinchem.2008.117143
14. Katzmann JA, Dispenzieri A, Kyle RA, Snyder MR, Plevak MF, Larson DR, Abraham RS, Lust JA, Melton LJ 3rd, Rajkumar SV. Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays. Mayo Clin Proc. 2006;81(12):1575-8. doi: 10.4065/81.12.1575
15. Hutchison C, Basnayake K, Cockwell P. Serum free light chain assessment in monoclonal gammopathy and kidney disease. Nat Rev Nephrol. 2009;5:621-7. doi: 10.1038/nrneph.2009.151
16. Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, Kyle RA. Serum reference intervals and diagnostic ranges for free and free immunoglobulin light chains: Relative sensitivity for detection of monoclonal light chains. Clin Chem. 2002;48(9):1437-44. PMID: 12194920
17. Dispenzieri A, Katzmann JA, Kyle RA, Larson DR, Melton LJ 3rd, Colby CL, Therneau TM, Clark R, Kumar SK, Bradwell A, Fonseca R, Jelinek DF, Rajkumar SV. Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: A retrospective population-based cohort study. Lancet. 2010;375:1721-8. doi: 10.1016/S0140-6736(10)60482-5
18. Keeling J, Herrera GA. Matrix metalloproteinases and mesangial remodeling in light chain-related glomerular damage. Kidney Int. 2005;68(4):1590-603. doi: 10.1111/j.1523-1755.2005.00571.x
19. Basnayake K, Stringer S, Hutchison C, Cockwell P. The biology of immunoglobulin free light chains and kidney injury. Kidney Int. 2011;79:1289-301. doi: 10.1038/ki.2011
20. Kapoulas S, Raptis V, Papaioannou M. New aspects on the pathogenesis of renal disorders related to monoclonal gammopathies. Nephrol Ther. 2015;11(3):135-43. doi: 10.1016/j.nephro.2014.12.005
21. Zhu L, Herrera GA, Murphy-Ullrich JE, Huang ZQ, Sanders PW. Pathogenesis of glomerulosclerosis in light chain deposition disease. Role for transforming growth factor-beta. Am J Pathol. 1995;147(2):375-85.
22. Russell WJ, Cardelli J, Harris E, Baier RJ, Herrera GA. Monoclonal light chain-mesangial cell interactions: early signaling events and subsequent pathologic effects. Lab Invest. 2001;81:689-703.
23. Teng J, Russell WJ, Gu X, Cardelli J, Jones ML, Herrera GA. Different types of glomerulopathic light chains interact with mesangial cells using a common receptor but exhibit different intracellular trafficking patterns. Lab Invest. 2004;84(4):440-51. doi: 10.1038/labinvest.3700069
24. Keeling J, Teng J, Herrera GA. AL-amyloidosis and light-chain deposition disease light chains induce divergent phenotypic transformations of human mesangial cells. Lab Invest. 2004;84(10):1322-38.
25. Meri S, Koistinen V, Miettinen A, Tornroth TG, Seppala IJT. Activation of the alternative pathaway of complement by monoclonal lambda L chains in membranoproliferative glomerulonephritis. J Exp Med. 1992;175:939-50.
26. Jokiranta TS, Solomon A, Pangburn MK, Zipfel PF, Meri S. Nephritogenic lambda light chain dimer: a unique human miniautoantibody against factor H. J Immunol. 1999;163:4590-6.
27. Knight GB, Gao L, Gragnani L, Elfahal MM, De Rosa FG, Gordon FD, Agnello V. Detection of WA B cells in hepatitis C virus infection: a potential prognostic marker for cryo-globulinemic vasculitis and B cell malignancies. Arthritis Rheum. 2010;62:2152-9. doi: 10.1002/art.27490
28. Wang PX, Sanders PW. Immunoglobulin light chains generate hydrogen peroxide. J Am Soc Nephrol. 2007;18(4):1239-45. doi: 10.1681/ASN.2006111299
29. Sethi S, Fervenza FC, Rajkumar SV. Spectrum of manifestations of monoclonal gammopathy-associated renal lesions. Curr Opin Nephrol Hypertens. 2016;25:127-37. doi: 10.1097/MNH.0000000000000201
30. Zakharova EV, Stolyarevich ES, Vorobyeva OA, Nikitin EA Combined immunoglobulin G kappa nephropathy: Monoclonal immunoglobulin deposition disease and proximal tubulopathy: monoclonal gammopathy of renal significance or smoldering multiple myeloma? Case report and review of literature. Integr Cancer Sci Therap. 2017;4(1):1-9. doi: 10.15761/ICST.1000225
2. Parry H, Pratt G, Hutchison C. Monoclonal gammopathy of undetermined significance: an update for nephrologists. Adv Chron Kidney Dis. 2012;19(5):291-6. doi: 10.1053/j.ackd.2012.07.006
3. Nasr SH, Satoskar A, Markowitz GS, Valeri AM, Appel GB, Stokes MB, Nadasdy T, D'Agati VD. Proliferative glomerulonephritis with monoclonal IgG deposits. J Am Soc Nephrol. 2009;20:2055-64. doi: 10.1681/ASN.2009010110
4. Bridoux F, Leung N, Hutchison CA, Touchard G, Sethi S, Fermand JP, Picken MM, Herrera GA, Kastritis E, Merlini G, Roussel M, Fervenza FC, Dispenzieri A, Kyle RA, Nasr SH; International Kidney and Monoclonal Gammopathy Research Group. Diagnosis of monoclonal gammopathy of renal significance. Kidney Int. 2015;87(4):698-711. doi: 10.1038/ki.2014.408
5. Hogan JJ, Weiss BM. Bridging the divide: an onco-nephrologic approach to the monoclonal gammopathies of renal significance. Clin J Am Soc Nephrol. 2016;11(9):1681-91. doi: 10.2215/CJN.03160316
6. Chauvet S, Frémeaux-Bacchi V, Petitprez F, Karras A, Daniel L, Burtey S, Choukroun G, Delmas Y, Guerrot D, François A, Le Quintrec M, Javaugue V, Ribes D, Vrigneaud L, Arnulf B, Goujon JM, Ronco P, Touchard G, Bridoux F. Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy-associated C3 glomerulopathy. Blood. 2017;129(11):1437-47. doi: 10.1182/blood-2016-08-737163
7. Willrich MAV, Murray DL, Kyle RA. Laboratory testing for monoclonal gammopathies: Focus on monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Clin Biochem. 2018;51:38-47. doi: 10.1016/j.clinbiochem.2017.05.001
8. Katzmann JA, Kyle RA, Benson J, Larson DR, Snyder MR, Lust JA, Rajkumar SV, Dispenzieri A. Screening panels for detection of monoclonal gammopathies. Clin Chem. 2009;55(8):1517-22. doi: 10.1373/clinchem.2009.126664
9. Dispenzieri A, Kyle R, Merlini G, Miguel JS, Ludwig H, Hajek R, Palumbo A, Jagannath S, Blade J, Lonial S, Dimopoulos M, Comenzo R, Einsele H, Barlogie B, Anderson K, Gertz M, Harousseau JL, Attal M, Tosi P, Sonneveld P, Boccadoro M, Morgan G, Richardson P, Sezer O, Mateos MV, Cavo M, Joshua D, Turesson I, Chen W, Shimizu K, Powles R, Rajkumar SV, Durie BG; International Myeloma Working Group. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 209;23:215-24. doi: 10.1038/leu.2008.307
10. Dimopoulos M, Kyle R, Fermand JP, Rajkumar SV, San Miguel J, Chanan-Khan A, Ludwig H, Joshua D, Mehta J, Gertz M, Avet-Loiseau H, Beksaç M, Anderson KC, Moreau P, Singhal S, Goldschmidt H, Boccadoro M, Kumar S, Giralt S, Munshi NC, Jagannath S; International Myeloma Workshop Consensus Panel 3. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood. 2011;117(18):4701-5. doi: 10.1182/blood-2010-10-299529
11. Hill PG, Forsyth JM, Rai B, Mayne S. Serum free light chains: an alternative test to urine Bence Jones proteins when screening for monoclonal gammopathies. Clin Chem. 2006;52:1743-8. doi: 10.1373/clinchem.2006.069104
12. Jenner E. Serum free light chains in clinical laboratory diagnostics. Clin Chim Acta. 2014;427:15-20. doi: 10.1016/j.cca.2013.08.018
13. Palladini G, Russo P, Bosoni T, Verga L, Sarais G, Lavatelli F, Nuvolone M, Obici L, Casarini S, Donadei S, Albertini R, Righetti G, Marini M, Graziani MS, Melzi D'Eril GV, Moratti R, Merlini G. Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem. 2009;55(3):499-504. doi: 10.1373/clinchem.2008.117143
14. Katzmann JA, Dispenzieri A, Kyle RA, Snyder MR, Plevak MF, Larson DR, Abraham RS, Lust JA, Melton LJ 3rd, Rajkumar SV. Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays. Mayo Clin Proc. 2006;81(12):1575-8. doi: 10.4065/81.12.1575
15. Hutchison C, Basnayake K, Cockwell P. Serum free light chain assessment in monoclonal gammopathy and kidney disease. Nat Rev Nephrol. 2009;5:621-7. doi: 10.1038/nrneph.2009.151
16. Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, Kyle RA. Serum reference intervals and diagnostic ranges for free and free immunoglobulin light chains: Relative sensitivity for detection of monoclonal light chains. Clin Chem. 2002;48(9):1437-44. PMID: 12194920
17. Dispenzieri A, Katzmann JA, Kyle RA, Larson DR, Melton LJ 3rd, Colby CL, Therneau TM, Clark R, Kumar SK, Bradwell A, Fonseca R, Jelinek DF, Rajkumar SV. Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: A retrospective population-based cohort study. Lancet. 2010;375:1721-8. doi: 10.1016/S0140-6736(10)60482-5
18. Keeling J, Herrera GA. Matrix metalloproteinases and mesangial remodeling in light chain-related glomerular damage. Kidney Int. 2005;68(4):1590-603. doi: 10.1111/j.1523-1755.2005.00571.x
19. Basnayake K, Stringer S, Hutchison C, Cockwell P. The biology of immunoglobulin free light chains and kidney injury. Kidney Int. 2011;79:1289-301. doi: 10.1038/ki.2011
20. Kapoulas S, Raptis V, Papaioannou M. New aspects on the pathogenesis of renal disorders related to monoclonal gammopathies. Nephrol Ther. 2015;11(3):135-43. doi: 10.1016/j.nephro.2014.12.005
21. Zhu L, Herrera GA, Murphy-Ullrich JE, Huang ZQ, Sanders PW. Pathogenesis of glomerulosclerosis in light chain deposition disease. Role for transforming growth factor-beta. Am J Pathol. 1995;147(2):375-85.
22. Russell WJ, Cardelli J, Harris E, Baier RJ, Herrera GA. Monoclonal light chain-mesangial cell interactions: early signaling events and subsequent pathologic effects. Lab Invest. 2001;81:689-703.
23. Teng J, Russell WJ, Gu X, Cardelli J, Jones ML, Herrera GA. Different types of glomerulopathic light chains interact with mesangial cells using a common receptor but exhibit different intracellular trafficking patterns. Lab Invest. 2004;84(4):440-51. doi: 10.1038/labinvest.3700069
24. Keeling J, Teng J, Herrera GA. AL-amyloidosis and light-chain deposition disease light chains induce divergent phenotypic transformations of human mesangial cells. Lab Invest. 2004;84(10):1322-38.
25. Meri S, Koistinen V, Miettinen A, Tornroth TG, Seppala IJT. Activation of the alternative pathaway of complement by monoclonal lambda L chains in membranoproliferative glomerulonephritis. J Exp Med. 1992;175:939-50.
26. Jokiranta TS, Solomon A, Pangburn MK, Zipfel PF, Meri S. Nephritogenic lambda light chain dimer: a unique human miniautoantibody against factor H. J Immunol. 1999;163:4590-6.
27. Knight GB, Gao L, Gragnani L, Elfahal MM, De Rosa FG, Gordon FD, Agnello V. Detection of WA B cells in hepatitis C virus infection: a potential prognostic marker for cryo-globulinemic vasculitis and B cell malignancies. Arthritis Rheum. 2010;62:2152-9. doi: 10.1002/art.27490
28. Wang PX, Sanders PW. Immunoglobulin light chains generate hydrogen peroxide. J Am Soc Nephrol. 2007;18(4):1239-45. doi: 10.1681/ASN.2006111299
29. Sethi S, Fervenza FC, Rajkumar SV. Spectrum of manifestations of monoclonal gammopathy-associated renal lesions. Curr Opin Nephrol Hypertens. 2016;25:127-37. doi: 10.1097/MNH.0000000000000201
30. Zakharova EV, Stolyarevich ES, Vorobyeva OA, Nikitin EA Combined immunoglobulin G kappa nephropathy: Monoclonal immunoglobulin deposition disease and proximal tubulopathy: monoclonal gammopathy of renal significance or smoldering multiple myeloma? Case report and review of literature. Integr Cancer Sci Therap. 2017;4(1):1-9. doi: 10.15761/ICST.1000225
2. Parry H, Pratt G, Hutchison C. Monoclonal gammopathy of undetermined significance: an update for nephrologists. Adv Chron Kidney Dis. 2012;19(5):291-6. doi: 10.1053/j.ackd.2012.07.006
3. Nasr SH, Satoskar A, Markowitz GS, Valeri AM, Appel GB, Stokes MB, Nadasdy T, D'Agati VD. Proliferative glomerulonephritis with monoclonal IgG deposits. J Am Soc Nephrol. 2009;20:2055-64. doi: 10.1681/ASN.2009010110
4. Bridoux F, Leung N, Hutchison CA, Touchard G, Sethi S, Fermand JP, Picken MM, Herrera GA, Kastritis E, Merlini G, Roussel M, Fervenza FC, Dispenzieri A, Kyle RA, Nasr SH; International Kidney and Monoclonal Gammopathy Research Group. Diagnosis of monoclonal gammopathy of renal significance. Kidney Int. 2015;87(4):698-711. doi: 10.1038/ki.2014.408
5. Hogan JJ, Weiss BM. Bridging the divide: an onco-nephrologic approach to the monoclonal gammopathies of renal significance. Clin J Am Soc Nephrol. 2016;11(9):1681-91. doi: 10.2215/CJN.03160316
6. Chauvet S, Frémeaux-Bacchi V, Petitprez F, Karras A, Daniel L, Burtey S, Choukroun G, Delmas Y, Guerrot D, François A, Le Quintrec M, Javaugue V, Ribes D, Vrigneaud L, Arnulf B, Goujon JM, Ronco P, Touchard G, Bridoux F. Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy-associated C3 glomerulopathy. Blood. 2017;129(11):1437-47. doi: 10.1182/blood-2016-08-737163
7. Willrich MAV, Murray DL, Kyle RA. Laboratory testing for monoclonal gammopathies: Focus on monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Clin Biochem. 2018;51:38-47. doi: 10.1016/j.clinbiochem.2017.05.001
8. Katzmann JA, Kyle RA, Benson J, Larson DR, Snyder MR, Lust JA, Rajkumar SV, Dispenzieri A. Screening panels for detection of monoclonal gammopathies. Clin Chem. 2009;55(8):1517-22. doi: 10.1373/clinchem.2009.126664
9. Dispenzieri A, Kyle R, Merlini G, Miguel JS, Ludwig H, Hajek R, Palumbo A, Jagannath S, Blade J, Lonial S, Dimopoulos M, Comenzo R, Einsele H, Barlogie B, Anderson K, Gertz M, Harousseau JL, Attal M, Tosi P, Sonneveld P, Boccadoro M, Morgan G, Richardson P, Sezer O, Mateos MV, Cavo M, Joshua D, Turesson I, Chen W, Shimizu K, Powles R, Rajkumar SV, Durie BG; International Myeloma Working Group. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 209;23:215-24. doi: 10.1038/leu.2008.307
10. Dimopoulos M, Kyle R, Fermand JP, Rajkumar SV, San Miguel J, Chanan-Khan A, Ludwig H, Joshua D, Mehta J, Gertz M, Avet-Loiseau H, Beksaç M, Anderson KC, Moreau P, Singhal S, Goldschmidt H, Boccadoro M, Kumar S, Giralt S, Munshi NC, Jagannath S; International Myeloma Workshop Consensus Panel 3. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood. 2011;117(18):4701-5. doi: 10.1182/blood-2010-10-299529
11. Hill PG, Forsyth JM, Rai B, Mayne S. Serum free light chains: an alternative test to urine Bence Jones proteins when screening for monoclonal gammopathies. Clin Chem. 2006;52:1743-8. doi: 10.1373/clinchem.2006.069104
12. Jenner E. Serum free light chains in clinical laboratory diagnostics. Clin Chim Acta. 2014;427:15-20. doi: 10.1016/j.cca.2013.08.018
13. Palladini G, Russo P, Bosoni T, Verga L, Sarais G, Lavatelli F, Nuvolone M, Obici L, Casarini S, Donadei S, Albertini R, Righetti G, Marini M, Graziani MS, Melzi D'Eril GV, Moratti R, Merlini G. Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem. 2009;55(3):499-504. doi: 10.1373/clinchem.2008.117143
14. Katzmann JA, Dispenzieri A, Kyle RA, Snyder MR, Plevak MF, Larson DR, Abraham RS, Lust JA, Melton LJ 3rd, Rajkumar SV. Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays. Mayo Clin Proc. 2006;81(12):1575-8. doi: 10.4065/81.12.1575
15. Hutchison C, Basnayake K, Cockwell P. Serum free light chain assessment in monoclonal gammopathy and kidney disease. Nat Rev Nephrol. 2009;5:621-7. doi: 10.1038/nrneph.2009.151
16. Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, Kyle RA. Serum reference intervals and diagnostic ranges for free and free immunoglobulin light chains: Relative sensitivity for detection of monoclonal light chains. Clin Chem. 2002;48(9):1437-44. PMID: 12194920
17. Dispenzieri A, Katzmann JA, Kyle RA, Larson DR, Melton LJ 3rd, Colby CL, Therneau TM, Clark R, Kumar SK, Bradwell A, Fonseca R, Jelinek DF, Rajkumar SV. Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: A retrospective population-based cohort study. Lancet. 2010;375:1721-8. doi: 10.1016/S0140-6736(10)60482-5
18. Keeling J, Herrera GA. Matrix metalloproteinases and mesangial remodeling in light chain-related glomerular damage. Kidney Int. 2005;68(4):1590-603. doi: 10.1111/j.1523-1755.2005.00571.x
19. Basnayake K, Stringer S, Hutchison C, Cockwell P. The biology of immunoglobulin free light chains and kidney injury. Kidney Int. 2011;79:1289-301. doi: 10.1038/ki.2011
20. Kapoulas S, Raptis V, Papaioannou M. New aspects on the pathogenesis of renal disorders related to monoclonal gammopathies. Nephrol Ther. 2015;11(3):135-43. doi: 10.1016/j.nephro.2014.12.005
21. Zhu L, Herrera GA, Murphy-Ullrich JE, Huang ZQ, Sanders PW. Pathogenesis of glomerulosclerosis in light chain deposition disease. Role for transforming growth factor-beta. Am J Pathol. 1995;147(2):375-85.
22. Russell WJ, Cardelli J, Harris E, Baier RJ, Herrera GA. Monoclonal light chain-mesangial cell interactions: early signaling events and subsequent pathologic effects. Lab Invest. 2001;81:689-703.
23. Teng J, Russell WJ, Gu X, Cardelli J, Jones ML, Herrera GA. Different types of glomerulopathic light chains interact with mesangial cells using a common receptor but exhibit different intracellular trafficking patterns. Lab Invest. 2004;84(4):440-51. doi: 10.1038/labinvest.3700069
24. Keeling J, Teng J, Herrera GA. AL-amyloidosis and light-chain deposition disease light chains induce divergent phenotypic transformations of human mesangial cells. Lab Invest. 2004;84(10):1322-38.
25. Meri S, Koistinen V, Miettinen A, Tornroth TG, Seppala IJT. Activation of the alternative pathaway of complement by monoclonal lambda L chains in membranoproliferative glomerulonephritis. J Exp Med. 1992;175:939-50.
26. Jokiranta TS, Solomon A, Pangburn MK, Zipfel PF, Meri S. Nephritogenic lambda light chain dimer: a unique human miniautoantibody against factor H. J Immunol. 1999;163:4590-6.
27. Knight GB, Gao L, Gragnani L, Elfahal MM, De Rosa FG, Gordon FD, Agnello V. Detection of WA B cells in hepatitis C virus infection: a potential prognostic marker for cryo-globulinemic vasculitis and B cell malignancies. Arthritis Rheum. 2010;62:2152-9. doi: 10.1002/art.27490
28. Wang PX, Sanders PW. Immunoglobulin light chains generate hydrogen peroxide. J Am Soc Nephrol. 2007;18(4):1239-45. doi: 10.1681/ASN.2006111299
29. Sethi S, Fervenza FC, Rajkumar SV. Spectrum of manifestations of monoclonal gammopathy-associated renal lesions. Curr Opin Nephrol Hypertens. 2016;25:127-37. doi: 10.1097/MNH.0000000000000201
30. Zakharova EV, Stolyarevich ES, Vorobyeva OA, Nikitin EA Combined immunoglobulin G kappa nephropathy: Monoclonal immunoglobulin deposition disease and proximal tubulopathy: monoclonal gammopathy of renal significance or smoldering multiple myeloma? Case report and review of literature. Integr Cancer Sci Therap. 2017;4(1):1-9. doi: 10.15761/ICST.1000225
________________________________________________
2. Parry H, Pratt G, Hutchison C. Monoclonal gammopathy of undetermined significance: an update for nephrologists. Adv Chron Kidney Dis. 2012;19(5):291-6. doi: 10.1053/j.ackd.2012.07.006
3. Nasr SH, Satoskar A, Markowitz GS, Valeri AM, Appel GB, Stokes MB, Nadasdy T, D'Agati VD. Proliferative glomerulonephritis with monoclonal IgG deposits. J Am Soc Nephrol. 2009;20:2055-64. doi: 10.1681/ASN.2009010110
4. Bridoux F, Leung N, Hutchison CA, Touchard G, Sethi S, Fermand JP, Picken MM, Herrera GA, Kastritis E, Merlini G, Roussel M, Fervenza FC, Dispenzieri A, Kyle RA, Nasr SH; International Kidney and Monoclonal Gammopathy Research Group. Diagnosis of monoclonal gammopathy of renal significance. Kidney Int. 2015;87(4):698-711. doi: 10.1038/ki.2014.408
5. Hogan JJ, Weiss BM. Bridging the divide: an onco-nephrologic approach to the monoclonal gammopathies of renal significance. Clin J Am Soc Nephrol. 2016;11(9):1681-91. doi: 10.2215/CJN.03160316
6. Chauvet S, Frémeaux-Bacchi V, Petitprez F, Karras A, Daniel L, Burtey S, Choukroun G, Delmas Y, Guerrot D, François A, Le Quintrec M, Javaugue V, Ribes D, Vrigneaud L, Arnulf B, Goujon JM, Ronco P, Touchard G, Bridoux F. Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy-associated C3 glomerulopathy. Blood. 2017;129(11):1437-47. doi: 10.1182/blood-2016-08-737163
7. Willrich MAV, Murray DL, Kyle RA. Laboratory testing for monoclonal gammopathies: Focus on monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Clin Biochem. 2018;51:38-47. doi: 10.1016/j.clinbiochem.2017.05.001
8. Katzmann JA, Kyle RA, Benson J, Larson DR, Snyder MR, Lust JA, Rajkumar SV, Dispenzieri A. Screening panels for detection of monoclonal gammopathies. Clin Chem. 2009;55(8):1517-22. doi: 10.1373/clinchem.2009.126664
9. Dispenzieri A, Kyle R, Merlini G, Miguel JS, Ludwig H, Hajek R, Palumbo A, Jagannath S, Blade J, Lonial S, Dimopoulos M, Comenzo R, Einsele H, Barlogie B, Anderson K, Gertz M, Harousseau JL, Attal M, Tosi P, Sonneveld P, Boccadoro M, Morgan G, Richardson P, Sezer O, Mateos MV, Cavo M, Joshua D, Turesson I, Chen W, Shimizu K, Powles R, Rajkumar SV, Durie BG; International Myeloma Working Group. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 209;23:215-24. doi: 10.1038/leu.2008.307
10. Dimopoulos M, Kyle R, Fermand JP, Rajkumar SV, San Miguel J, Chanan-Khan A, Ludwig H, Joshua D, Mehta J, Gertz M, Avet-Loiseau H, Beksaç M, Anderson KC, Moreau P, Singhal S, Goldschmidt H, Boccadoro M, Kumar S, Giralt S, Munshi NC, Jagannath S; International Myeloma Workshop Consensus Panel 3. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood. 2011;117(18):4701-5. doi: 10.1182/blood-2010-10-299529
11. Hill PG, Forsyth JM, Rai B, Mayne S. Serum free light chains: an alternative test to urine Bence Jones proteins when screening for monoclonal gammopathies. Clin Chem. 2006;52:1743-8. doi: 10.1373/clinchem.2006.069104
12. Jenner E. Serum free light chains in clinical laboratory diagnostics. Clin Chim Acta. 2014;427:15-20. doi: 10.1016/j.cca.2013.08.018
13. Palladini G, Russo P, Bosoni T, Verga L, Sarais G, Lavatelli F, Nuvolone M, Obici L, Casarini S, Donadei S, Albertini R, Righetti G, Marini M, Graziani MS, Melzi D'Eril GV, Moratti R, Merlini G. Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem. 2009;55(3):499-504. doi: 10.1373/clinchem.2008.117143
14. Katzmann JA, Dispenzieri A, Kyle RA, Snyder MR, Plevak MF, Larson DR, Abraham RS, Lust JA, Melton LJ 3rd, Rajkumar SV. Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays. Mayo Clin Proc. 2006;81(12):1575-8. doi: 10.4065/81.12.1575
15. Hutchison C, Basnayake K, Cockwell P. Serum free light chain assessment in monoclonal gammopathy and kidney disease. Nat Rev Nephrol. 2009;5:621-7. doi: 10.1038/nrneph.2009.151
16. Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, Kyle RA. Serum reference intervals and diagnostic ranges for free and free immunoglobulin light chains: Relative sensitivity for detection of monoclonal light chains. Clin Chem. 2002;48(9):1437-44. PMID: 12194920
17. Dispenzieri A, Katzmann JA, Kyle RA, Larson DR, Melton LJ 3rd, Colby CL, Therneau TM, Clark R, Kumar SK, Bradwell A, Fonseca R, Jelinek DF, Rajkumar SV. Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: A retrospective population-based cohort study. Lancet. 2010;375:1721-8. doi: 10.1016/S0140-6736(10)60482-5
18. Keeling J, Herrera GA. Matrix metalloproteinases and mesangial remodeling in light chain-related glomerular damage. Kidney Int. 2005;68(4):1590-603. doi: 10.1111/j.1523-1755.2005.00571.x
19. Basnayake K, Stringer S, Hutchison C, Cockwell P. The biology of immunoglobulin free light chains and kidney injury. Kidney Int. 2011;79:1289-301. doi: 10.1038/ki.2011
20. Kapoulas S, Raptis V, Papaioannou M. New aspects on the pathogenesis of renal disorders related to monoclonal gammopathies. Nephrol Ther. 2015;11(3):135-43. doi: 10.1016/j.nephro.2014.12.005
21. Zhu L, Herrera GA, Murphy-Ullrich JE, Huang ZQ, Sanders PW. Pathogenesis of glomerulosclerosis in light chain deposition disease. Role for transforming growth factor-beta. Am J Pathol. 1995;147(2):375-85.
22. Russell WJ, Cardelli J, Harris E, Baier RJ, Herrera GA. Monoclonal light chain-mesangial cell interactions: early signaling events and subsequent pathologic effects. Lab Invest. 2001;81:689-703.
23. Teng J, Russell WJ, Gu X, Cardelli J, Jones ML, Herrera GA. Different types of glomerulopathic light chains interact with mesangial cells using a common receptor but exhibit different intracellular trafficking patterns. Lab Invest. 2004;84(4):440-51. doi: 10.1038/labinvest.3700069
24. Keeling J, Teng J, Herrera GA. AL-amyloidosis and light-chain deposition disease light chains induce divergent phenotypic transformations of human mesangial cells. Lab Invest. 2004;84(10):1322-38.
25. Meri S, Koistinen V, Miettinen A, Tornroth TG, Seppala IJT. Activation of the alternative pathaway of complement by monoclonal lambda L chains in membranoproliferative glomerulonephritis. J Exp Med. 1992;175:939-50.
26. Jokiranta TS, Solomon A, Pangburn MK, Zipfel PF, Meri S. Nephritogenic lambda light chain dimer: a unique human miniautoantibody against factor H. J Immunol. 1999;163:4590-6.
27. Knight GB, Gao L, Gragnani L, Elfahal MM, De Rosa FG, Gordon FD, Agnello V. Detection of WA B cells in hepatitis C virus infection: a potential prognostic marker for cryo-globulinemic vasculitis and B cell malignancies. Arthritis Rheum. 2010;62:2152-9. doi: 10.1002/art.27490
28. Wang PX, Sanders PW. Immunoglobulin light chains generate hydrogen peroxide. J Am Soc Nephrol. 2007;18(4):1239-45. doi: 10.1681/ASN.2006111299
29. Sethi S, Fervenza FC, Rajkumar SV. Spectrum of manifestations of monoclonal gammopathy-associated renal lesions. Curr Opin Nephrol Hypertens. 2016;25:127-37. doi: 10.1097/MNH.0000000000000201
30. Zakharova EV, Stolyarevich ES, Vorobyeva OA, Nikitin EA Combined immunoglobulin G kappa nephropathy: Monoclonal immunoglobulin deposition disease and proximal tubulopathy: monoclonal gammopathy of renal significance or smoldering multiple myeloma? Case report and review of literature. Integr Cancer Sci Therap. 2017;4(1):1-9. doi: 10.15761/ICST.1000225
Авторы
Л.В. Козловская (Лысенко)1, Н.В. Чеботарева1, Н.Н. Мрыхин1, В.В. Рамеев1, Т.В. Андросова1, С.В. Рощупкина1, С.А. Марьина2, И.Н. Когарко3, Б.С. Когарко3
1 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
2 ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России, Москва, Россия;
3 ФГБУН «Институт химической физики им. Н.Н. Семенова» Российской академии наук, Москва, Россия
1 Sechenov First Moscow State Medical University of the Ministry (Sechenov University), Moscow, Russia;
2 National Research Center for Hematology of the Ministry of Health of the Russian Federation, Moscow, Russia;
3 Semenov Institute of Chemical Physics of the Russian Academy of Sciences, Moscow, Russia
1 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
2 ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России, Москва, Россия;
3 ФГБУН «Институт химической физики им. Н.Н. Семенова» Российской академии наук, Москва, Россия
________________________________________________
1 Sechenov First Moscow State Medical University of the Ministry (Sechenov University), Moscow, Russia;
2 National Research Center for Hematology of the Ministry of Health of the Russian Federation, Moscow, Russia;
3 Semenov Institute of Chemical Physics of the Russian Academy of Sciences, Moscow, Russia
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