Skip to main content

Advertisement

Log in

An update to the pathogenesis for monoclonal gammopathy of renal significance

Annals of Hematology Aims and scope Submit manuscript

Abstract

Monoclonal gammopathy of renal significance (MGRS) is characterized by the nephrotoxic monoclonal immunoglobulin secreted by an otherwise asymptomatic or indolent B cell or plasma cell clone, without hematologic criteria for treatment. These MGRS-associated diseases can involve one or more renal compartments, including glomeruli, tubules, and vessels. Hydrophobic residue replacement, N-glycosylated, increase in isoelectric point in monoclonal immunoglobulin (MIg) causes it to transform from soluble form to tissue deposition, and consequently resulting in glomerular damage. In addition to MIg deposition, complement deposition is also found in C3 glomerulopathy with monoclonal glomerulopathy, which is caused by an abnormality of the alternative pathway and may involve multiple factors including complement component 3 nephritic factor, anti-complement factor auto-antibodies, or MIg which directly cleaves C3. Furthermore, inflammatory factors, growth factors, and virus infection may also participate in the development of the diseases. In this review, for the first time, we discussed current highlights in the mechanism of MGRS-related lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Sethi S, Rajkumar SV, D’Agati VD (2018) The complexity and heterogeneity of monoclonal immunoglobulin-associated renal diseases. J Am Soc Nephrol 29(7):1810–1823. https://doi.org/10.1681/ASN.2017121319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR, Dispenzieri A, Katzmann JA, Melton LJ 3rd (2006) Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med 354(13):1362–1369. https://doi.org/10.1056/NEJMoa054494

    Article  CAS  PubMed  Google Scholar 

  3. Leung N, Bridoux F, Hutchison CA, Nasr SH, Cockwell P, Fermand JP, Dispenzieri A, Song KW, Kyle RA, International K, Monoclonal Gammopathy Research G (2012) Monoclonal gammopathy of renal significance: when MGUS is no longer undetermined or insignificant. Blood 120(22):4292–4295. https://doi.org/10.1182/blood-2012-07-445304

    Article  CAS  PubMed  Google Scholar 

  4. Fermand JP, Bridoux F, Kyle RA, Kastritis E, Weiss BM, Cook MA, Drayson MT, Dispenzieri A, Leung N, International K, Monoclonal Gammopathy Research G (2013) How I treat monoclonal gammopathy of renal significance (MGRS). Blood 122(22):3583–3590. https://doi.org/10.1182/blood-2013-05-495,929

    Article  CAS  PubMed  Google Scholar 

  5. Chauvet S, Fremeaux-Bacchi V, Petitprez F, Karras A, Daniel L, Burtey S, Choukroun G, Delmas Y, Guerrot D, Francois A, Le Quintrec M, Javaugue V, Ribes D, Vrigneaud L, Arnulf B, Goujon JM, Ronco P, Touchard G, Bridoux F (2017) Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy-associated C3 glomerulopathy. Blood 129(11):1437–1447. https://doi.org/10.1182/blood-2016-08-737,163

    Article  CAS  PubMed  Google Scholar 

  6. Leung N, Bridoux F, Batuman V, Chaidos A, Cockwell P, D’Agati VD, Dispenzieri A, Fervenza FC, Fermand JP, Gibbs S, Gillmore JD, Herrera GA, Jaccard A, Jevremovic D, Kastritis E, Kukreti V, Kyle RA, Lachmann HJ, Larsen CP, Ludwig H, Markowitz GS, Merlini G, Mollee P, Picken MM, Rajkumar VS, Royal V, Sanders PW, Sethi S, Venner CP, Voorhees PM, Wechalekar AD, Weiss BM, Nasr SH (2019) The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group. Nat Rev Nephrol 15(1):45–59. https://doi.org/10.1038/s41581-018-0077-4

    Article  PubMed  Google Scholar 

  7. Nasr SH, Collins AB, Alexander MP, Schraith DF, Herrera Hernandez L, Fidler ME, Sethi S, Leung N, Fervenza FC, Cornell LD (2016) The clinicopathologic characteristics and outcome of atypical anti-glomerular basement membrane nephritis. Kidney Int 89(4):897–908. https://doi.org/10.1016/j.kint.2016.02.001

    Article  PubMed  Google Scholar 

  8. Best Rocha A, Larsen CP (2017) Membranous glomerulopathy with light chain-restricted deposits: a clinicopathological analysis of 28 cases. Kidney Int Rep 2(6):1141–1148. https://doi.org/10.1016/j.ekir.2017.07.008

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ravindran A, Go RS, Fervenza FC, Sethi S (2017) Thrombotic microangiopathy associated with monoclonal gammopathy. Kidney Int 91(3):691–698. https://doi.org/10.1016/j.kint.2016.09.045

    Article  PubMed  Google Scholar 

  10. Blanc C, Togarsimalemath SK, Chauvet S, Le Quintrec M, Moulin B, Buchler M, Jokiranta TS, Roumenina LT, Fremeaux-Bacchi V, Dragon-Durey MA (2015) Anti-factor H autoantibodies in C3 glomerulopathies and in atypical hemolytic uremic syndrome: one target, two diseases. J Immunol 194(11):5129–5138. https://doi.org/10.4049/jimmunol.1402770

    Article  CAS  PubMed  Google Scholar 

  11. Leung N, Buadi FK, Song KW, Magil AB, Cornell LD (2010) A case of bilateral renal arterial thrombosis associated with cryocrystalglobulinaemia. NDT Plus 3(1):74–77. https://doi.org/10.1093/ndtplus/sfp140

    Article  PubMed  Google Scholar 

  12. Ravindran A, Fervenza FC, Smith RJH, Sethi S (2018) C3 glomerulopathy associated with monoclonal Ig is a distinct subtype. Kidney Int 94(1):178–186. https://doi.org/10.1016/j.kint.2018.01.037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bomback AS, Appel GB (2012) Pathogenesis of the C3 glomerulopathies and reclassification of MPGN. Nat Rev Nephrol 8(11):634–642. https://doi.org/10.1038/nrneph.2012.213

    Article  CAS  PubMed  Google Scholar 

  14. Servais A, Noel LH, Roumenina LT, Le Quintrec M, Ngo S, Dragon-Durey MA, Macher MA, Zuber J, Karras A, Provot F, Moulin B, Grunfeld JP, Niaudet P, Lesavre P, Fremeaux-Bacchi V (2012) Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int 82(4):454–464. https://doi.org/10.1038/ki.2012.63

    Article  CAS  PubMed  Google Scholar 

  15. Ricklin D, Hajishengallis G, Yang K, Lambris JD (2010) Complement: a key system for immune surveillance and homeostasis. Nat Immunol 11(9):785–797. https://doi.org/10.1038/ni.1923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Noris M, Remuzzi G (2015) Glomerular diseases dependent on complement activation, including atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis, and C3 glomerulopathy: core curriculum 2015. Am J Kidney Dis 66(2):359–375. https://doi.org/10.1053/j.ajkd.2015.03.040

    Article  PubMed  PubMed Central  Google Scholar 

  17. Pickering MC, Cook HT, Warren J, Bygrave AE, Moss J, Walport MJ, Botto M (2002) Uncontrolled C3 activation causes membranoproliferative glomerulonephritis in mice deficient in complement factor H. Nat Genet 31(4):424–428. https://doi.org/10.1038/ng912

    Article  CAS  PubMed  Google Scholar 

  18. Chauvet S, Roumenina LT, Aucouturier P, Marinozzi MC, Dragon-Durey MA, Karras A, Delmas Y, Le Quintrec M, Guerrot D, Jourde-Chiche N, Ribes D, Ronco P, Bridoux F, Fremeaux-Bacchi V (2018) Both monoclonal and polyclonal immunoglobulin contingents mediate complement activation in monoclonal gammopathy associated-C3 glomerulopathy. Front Immunol 9:2260. https://doi.org/10.3389/fimmu.2018.02260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Martinez-Barricarte R, Heurich M, Valdes-Canedo F, Vazquez-Martul E, Torreira E, Montes T, Tortajada A, Pinto S, Lopez-Trascasa M, Morgan BP, Llorca O, Harris CL, Rodriguez de Cordoba S (2010) Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation. J Clin Invest 120(10):3702–3712. https://doi.org/10.1172/JCI43343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gale DP, de Jorge EG, Cook HT, Martinez-Barricarte R, Hadjisavvas A, McLean AG, Pusey CD, Pierides A, Kyriacou K, Athanasiou Y, Voskarides K, Deltas C, Palmer A, Frémeaux-Bacchi V, de Cordoba SR, Maxwell PH, Pickering MC (2010) Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with glomerulonephritis. Lancet 376(9743):794–801. https://doi.org/10.1016/s0140-6736(10)60670-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Habbig S, Mihatsch MJ, Heinen S, Beck B, Emmel M, Skerka C, Kirschfink M, Hoppe B, Zipfel PF, Licht C (2009) C3 deposition glomerulopathy due to a functional factor H defect. Kidney Int 75(11):1230–1234. https://doi.org/10.1038/ki.2008.354

    Article  PubMed  Google Scholar 

  22. Ruseva MM, Vernon KA, Lesher AM, Schwaeble WJ, Ali YM, Botto M, Cook T, Song W, Stover CM, Pickering MC (2013) Loss of properdin exacerbates C3 glomerulopathy resulting from factor H deficiency. J Am Soc Nephrol 24(1):43–52. https://doi.org/10.1681/ASN.2012060571

    Article  CAS  PubMed  Google Scholar 

  23. Marinozzi MC, Chauvet S, Le Quintrec M, Mignotet M, Petitprez F, Legendre C, Cailliez M, Deschenes G, Fischbach M, Karras A, Nobili F, Pietrement C, Dragon-Durey MA, Fakhouri F, Roumenina LT, Fremeaux-Bacchi V (2017) C5 nephritic factors drive the biological phenotype of C3 glomerulopathies. Kidney Int 92(5):1232–1241. https://doi.org/10.1016/j.kint.2017.04.017

    Article  CAS  PubMed  Google Scholar 

  24. Sethi S, Sukov WR, Zhang Y, Fervenza FC, Lager DJ, Miller DV, Cornell LD, Krishnan SG, Smith RJ (2010) Dense deposit disease associated with monoclonal gammopathy of undetermined significance. Am J Kidney Dis 56(5):977–982. https://doi.org/10.1053/j.ajkd.2010.06.021

    Article  PubMed  PubMed Central  Google Scholar 

  25. Zand L, Kattah A, Fervenza FC, Smith RJ, Nasr SH, Zhang Y, Vrana JA, Leung N, Cornell LD, Sethi S (2013) C3 glomerulonephritis associated with monoclonal gammopathy: a case series. Am J Kidney Dis 62(3):506–514. https://doi.org/10.1053/j.ajkd.2013.02.370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chauvet S, Roumenina LT, Bruneau S, Marinozzi MC, Rybkine T, Schramm EC, Java A, Atkinson JP, Aldigier JC, Bridoux F, Touchard G, Fremeaux-Bacchi V (2016) A familial C3GN secondary to defective C3 regulation by complement receptor 1 and complement factor H. J Am Soc Nephrol 27(6):1665–1677. https://doi.org/10.1681/ASN.2015040348

    Article  CAS  PubMed  Google Scholar 

  27. Ito N, Ohashi R, Nagata M (2017) C3 glomerulopathy and current dilemmas. Clin Exp Nephrol 21(4):541–551. https://doi.org/10.1007/s10157-016-1358-5

    Article  CAS  PubMed  Google Scholar 

  28. Sethi S, Rajkumar SV (2013) Monoclonal gammopathy-associated proliferative glomerulonephritis. Mayo Clin Proc 88(11):1284–1293. https://doi.org/10.1016/j.mayocp.2013.08.002

    Article  PubMed  Google Scholar 

  29. Joly F, Cohen C, Javaugue V, Bender S, Belmouaz M, Arnulf B, Knebelmann B, Nouvier M, Audard V, Provot F, Gnemmi V, Nochy D, Goujon JM, Jaccard A, Touchard G, Fermand JP, Sirac C, Bridoux F (2019) Randall-type monoclonal immunoglobulin deposition disease: novel insights from a nationwide cohort study. Blood 133(6):576–587. https://doi.org/10.1182/blood-2018-09-872028

    Article  CAS  PubMed  Google Scholar 

  30. Nasr SH, Valeri AM, Cornell LD, Fidler ME, Sethi S, D’Agati VD, Leung N (2012) Renal monoclonal immunoglobulin deposition disease: a report of 64 patients from a single institution. Clin J Am Soc Nephrol 7(2):231–239. https://doi.org/10.2215/CJN.08640811

    Article  PubMed  Google Scholar 

  31. Lin J, Markowitz GS, Valeri AM, Kambham N, Sherman WH, Appel GB, D’Agati VD (2001) Renal monoclonal immunoglobulin deposition disease: the disease spectrum. J Am Soc Nephrol 12(7):1482–1492

    CAS  PubMed  Google Scholar 

  32. Buxbaum JN, Chuba JV, Hellman GC, Solomon A, Gallo GR (1990) Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis. Ann Intern Med 112(6):455–464

    Article  CAS  PubMed  Google Scholar 

  33. Confalonieri R, Barbiano di Belgiojoso G, Banfi G, Ferrario F, Bertani T, Pozzi C, Casanova S, Lupo A, De Ferrari G, Minetti L (1988) Light chain nephropathy: histological and clinical aspects in 15 cases. Nephrol Dial Transplant 3(2):150–156

    CAS  PubMed  Google Scholar 

  34. Cogne M, Preud’homme JL, Bauwens M, Touchard G, Aucouturier P (1991) Structure of a monoclonal kappa chain of the V kappa IV subgroup in the kidney and plasma cells in light chain deposition disease. J Clin Invest 87(6):2186–2190. https://doi.org/10.1172/JCI115252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Denoroy L, Deret S, Aucouturier P (1994) Overrepresentation of the V kappa IV subgroup in light chain deposition disease. Immunol Lett 42(1–2):63–66

    Article  CAS  PubMed  Google Scholar 

  36. Deret S, Chomilier J, Huang DB, Preud’homme JL, Stevens FJ, Aucouturier P (1997) Molecular modeling of immunoglobulin light chains implicates hydrophobic residues in non-amyloid light chain deposition disease. Protein Eng 10(10):1191–1197

    Article  CAS  PubMed  Google Scholar 

  37. Gallo G, Goni F, Boctor F, Vidal R, Kumar A, Stevens FJ, Frangione B, Ghiso J (1996) Light chain cardiomyopathy. Structural analysis of the light chain tissue deposits. Am J Pathol 148(5):1397–1406

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Teng J, Russell WJ, Gu X, Cardelli J, Jones ML, Herrera GA (2004) Different types of glomerulopathic light chains interact with mesangial cells using a common receptor but exhibit different intracellular trafficking patterns. Lab Investig 84(4):440–451. https://doi.org/10.1038/labinvest.3700069

    Article  CAS  PubMed  Google Scholar 

  39. Wang Q, Jiang F, Xu G (2019) The pathogenesis of renal injury and treatment in light chain deposition disease. J Transl Med 17(1):387–387. https://doi.org/10.1186/s12967-019-02147-4

    Article  PubMed  PubMed Central  Google Scholar 

  40. Basnayake K, Stringer SJ, Hutchison CA, Cockwell P (2011) The biology of immunoglobulin free light chains and kidney injury. Kidney Int 79(12):1289–1301. https://doi.org/10.1038/ki.2011.94

    Article  CAS  PubMed  Google Scholar 

  41. Russell WJ, Cardelli J, Harris E, Baier RJ, Herrera GA (2001) Monoclonal light chain--mesangial cell interactions: early signaling events and subsequent pathologic effects. Lab Investig 81(5):689–703

    Article  CAS  PubMed  Google Scholar 

  42. Duque N, Gomez-Guerrero C, Egido J (1997) Interaction of IgA with fc alpha receptors of human mesangial cells activates transcription factor nuclear factor-kappa B and induces expression and synthesis of monocyte chemoattractant protein-1, IL-8, and IFN-inducible protein 10. J Immunol 159(7):3474–3482

    CAS  PubMed  Google Scholar 

  43. Keeling J, Herrera GA (2009) An in vitro model of light chain deposition disease. Kidney Int 75(6):634–645. https://doi.org/10.1038/ki.2008.504

    Article  CAS  PubMed  Google Scholar 

  44. Isaac J, Kerby JD, Russell WJ, Dempsey SC, Sanders PW, Herrera GA (1998) In vitro modulation of AL-amyloid formation by human mesangial cells exposed to amyloidogenic light chains. Amyloid 5(4):238–246

    Article  CAS  PubMed  Google Scholar 

  45. Zhu L, Herrera GA, Murphy-Ullrich JE, Huang ZQ, Sanders PW (1995) Pathogenesis of glomerulosclerosis in light chain deposition disease. Role for transforming growth factor-beta. Am J Pathol 147(2):375–385

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Teng J, Zhang PL, Russell WJ, Zheng LP, Jones ML, Herrera GA (2003) Insights into mechanisms responsible for mesangial alterations associated with fibrogenic glomerulopathic light chains. Nephron Physiol 94(2):p28–p38. https://doi.org/10.1159/000071288

    Article  PubMed  Google Scholar 

  47. Keeling J, Herrera GA (2005) Matrix metalloproteinases and mesangial remodeling in light chain-related glomerular damage. Kidney Int 68(4):1590–1603. https://doi.org/10.1111/j.1523-1755.2005.00571.x

    Article  CAS  PubMed  Google Scholar 

  48. Keeling J, Teng J, Herrera GA (2004) AL-amyloidosis and light-chain deposition disease light chains induce divergent phenotypic transformations of human mesangial cells. Lab Investig 84(10):1322–1338. https://doi.org/10.1038/labinvest.3700161

    Article  CAS  PubMed  Google Scholar 

  49. Soma J, Sato K, Sakuma T, Saito H, Sato H, Sato T, Abbas A, Aucouturier P (2004) Immunoglobulin gamma3-heavy-chain deposition disease: report of a case and relationship with hypocomplementemia. Am J Kidney Dis 43(1):E10–E16

    Article  PubMed  Google Scholar 

  50. Bridoux F, Javaugue V, Bender S, Leroy F, Aucouturier P, Debiais-Delpech C, Goujon JM, Quellard N, Bonaud A, Clavel M, Trouillas P, Di Meo F, Gombert JM, Fermand JP, Jaccard A, Cogne M, Touchard G, Sirac C (2017) Unravelling the immunopathological mechanisms of heavy chain deposition disease with implications for clinical management. Kidney Int 91(2):423–434. https://doi.org/10.1016/j.kint.2016.09.004

    Article  CAS  PubMed  Google Scholar 

  51. Cheng IK, Ho SK, Chan DT, Ng WK, Chan KW (1996) Crescentic nodular glomerulosclerosis secondary to truncated immunoglobulin alpha heavy chain deposition. Am J Kidney Dis 28(2):283–288

    Article  CAS  PubMed  Google Scholar 

  52. Hendershot L, Bole D, Kohler G, Kearney JF (1987) Assembly and secretion of heavy chains that do not associate posttranslationally with immunoglobulin heavy chain-binding protein. J Cell Biol 104(3):761–767

    Article  CAS  PubMed  Google Scholar 

  53. Bonaud A, Bender S, Touchard G, Lacombe C, Srour N, Delpy L, Oblet C, Druilhe A, Quellard N, Javaugue V, Cogne M, Bridoux F, Sirac C (2015) A mouse model recapitulating human monoclonal heavy chain deposition disease evidences the relevance of proteasome inhibitor therapy. Blood 126(6):757–765. https://doi.org/10.1182/blood-2015-03-630277

    Article  CAS  PubMed  Google Scholar 

  54. Preud’homme JL, Aucouturier P, Touchard G, Striker L, Khamlichi AA, Rocca A, Denoroy L, Cogne M (1994) Monoclonal immunoglobulin deposition disease (Randall type). Relationship with structural abnormalities of immunoglobulin chains. Kidney Int 46(4):965–972

    Article  PubMed  Google Scholar 

  55. Kaplan B, Livneh A, Gallo G (2007) Charge differences between in vivo deposits in immunoglobulin light chain amyloidosis and non-amyloid light chain deposition disease. Br J Haematol 136(5):723–728. https://doi.org/10.1111/j.1365-2141.2006.06488.x

    Article  CAS  PubMed  Google Scholar 

  56. Bender S, Ayala MV, Javaugue V, Bonaud A, Cogne M, Touchard G, Jaccard A, Bridoux F, Sirac C (2018) Comprehensive molecular characterization of a heavy chain deposition disease case. Haematologica 103(11):e557–e560. https://doi.org/10.3324/haematol.2018.196113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Said SM, Sethi S, Valeri AM, Leung N, Cornell LD, Fidler ME, Herrera Hernandez L, Vrana JA, Theis JD, Quint PS, Dogan A, Nasr SH (2013) Renal amyloidosis: origin and clinicopathologic correlations of 474 recent cases. Clin J Am Soc Nephrol 8(9):1515–1523. https://doi.org/10.2215/CJN.10491012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Merlini G, Bellotti V (2003) Molecular mechanisms of amyloidosis. N Engl J Med 349(6):583–596. https://doi.org/10.1056/NEJMra023144

    Article  CAS  PubMed  Google Scholar 

  59. Dember LM (2006) Amyloidosis-associated kidney disease. J Am Soc Nephrol 17(12):3458–3471. https://doi.org/10.1681/ASN.2006050460

    Article  CAS  PubMed  Google Scholar 

  60. Tennent GA, Lovat LB, Pepys MB (1995) Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis. Proc Natl Acad Sci U S A 92(10):4299–4303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Brouet JC, Clauvel JP, Danon F, Klein M, Seligmann M (1974) Biologic and clinical significance of cryoglobulins. A report of 86 cases. Am J Med 57(5):775–788

    Article  CAS  PubMed  Google Scholar 

  62. Trejo O, Ramos-Casals M, Garcia-Carrasco M, Yague J, Jimenez S, de la Red G, Cervera R, Font J, Ingelmo M (2001) Cryoglobulinemia: study of etiologic factors and clinical and immunologic features in 443 patients from a single center. Medicine (Baltimore) 80(4):252–262

    Article  CAS  Google Scholar 

  63. Ramos-Casals M, Stone JH, Cid MC, Bosch X (2012) The cryoglobulinaemias. Lancet 379(9813):348–360. https://doi.org/10.1016/s0140-6736(11)60242-0

    Article  CAS  PubMed  Google Scholar 

  64. Ramos-Casals M, De Vita S, Tzioufas AG (2005) Hepatitis C virus, Sjogren’s syndrome and B-cell lymphoma: linking infection, autoimmunity and cancer. Autoimmun Rev 4(1):8–15. https://doi.org/10.1016/j.autrev.2004.04.004

    Article  PubMed  Google Scholar 

  65. Nishimura Y, Nakamura H (1984) Human monoclonal cryoimmunoglobulins. I. Molecular properties of IgG3 kappa (Jir protein) and the cryo-coprecipitability of its molecular fragments by papain. J Biochem 95(1):255–265. https://doi.org/10.1093/oxfordjournals.jbchem.a134592

    Article  CAS  PubMed  Google Scholar 

  66. Spertini F, Coulie PG, Van Snick J, Davidson E, Lambert PH, Izui S (1989) Inhibition of cryoprecipitation of murine IgG3 anti-dinitrophenyl (DNP) monoclonal antibodies by anionic DNP-amino acid conjugates. Eur J Immunol 19(2):273–278. https://doi.org/10.1002/eji.1830190209

    Article  CAS  PubMed  Google Scholar 

  67. Strevey J, Beaulieu AD, Menard C, Valet JP, Latulippe L, Hebert J (1984) The role of fibronectin in the cryoprecipitation of monoclonal cryoglobulins. Clin Exp Immunol 55(2):340–346

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Otani M, Kuroki A, Kikuchi S, Kihara M, Nakata J, Ito K, Furukawa J, Shinohara Y, Izui S (2012) Sialylation determines the nephritogenicity of IgG3 cryoglobulins. J Am Soc Nephrol 23(11):1869–1878. https://doi.org/10.1681/ASN.2012050477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kuroda Y, Kuroki A, Kikuchi S, Funase T, Nakata M, Izui S (2005) A critical role for sialylation in cryoglobulin activity of murine IgG3 monoclonal antibodies. J Immunol 175(2):1056–1061. https://doi.org/10.4049/jimmunol.175.2.1056

    Article  CAS  PubMed  Google Scholar 

  70. Sanders PW (2012) Mechanisms of light chain injury along the tubular nephron. J Am Soc Nephrol 23(11):1777–1781. https://doi.org/10.1681/ASN.2012040388

    Article  CAS  PubMed  Google Scholar 

  71. Stokes MB, Valeri AM, Herlitz L, Khan AM, Siegel DS, Markowitz GS, D’Agati VD (2016) Light chain proximal tubulopathy: clinical and pathologic characteristics in the modern treatment era. J Am Soc Nephrol 27(5):1555–1565. https://doi.org/10.1681/ASN.2015020185

    Article  CAS  PubMed  Google Scholar 

  72. Sirac C, Bridoux F, Carrion C, Devuyst O, Fernandez B, Goujon JM, El Hamel C, Aldigier JC, Touchard G, Cogne M (2006) Role of the monoclonal kappa chain V domain and reversibility of renal damage in a transgenic model of acquired Fanconi syndrome. Blood 108(2):536–543. https://doi.org/10.1182/blood-2005-11-4419

    Article  CAS  PubMed  Google Scholar 

  73. Herlitz LC, Roglieri J, Resta R, Bhagat G, Markowitz GS (2009) Light chain proximal tubulopathy. Kidney Int 76(7):792–797. https://doi.org/10.1038/ki.2008.666

    Article  PubMed  Google Scholar 

  74. Wang PX, Sanders PW (2007) Immunoglobulin light chains generate hydrogen peroxide. J Am Soc Nephrol 18(4):1239–1245. https://doi.org/10.1681/ASN.2006111299

    Article  CAS  PubMed  Google Scholar 

  75. Basnayake K, Ying WZ, Wang PX, Sanders PW (2010) Immunoglobulin light chains activate tubular epithelial cells through redox signaling. J Am Soc Nephrol 21(7):1165–1173. https://doi.org/10.1681/ASN.2009101089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Ying WZ, Wang PX, Aaron KJ, Basnayake K, Sanders PW (2011) Immunoglobulin light chains activate nuclear factor-kappaB in renal epithelial cells through a Src-dependent mechanism. Blood 117(4):1301–1307. https://doi.org/10.1182/blood-2010-08-302505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ying WZ, Li X, Rangarajan S, Feng W, Curtis LM, Sanders PW (2019) Immunoglobulin light chains generate pro-inflammatory and pro-fibrotic kidney injury. J Clin Invest. https://doi.org/10.1172/JCI125517

  78. Ma FY, Tesch GH, Nikolic-Paterson DJ (2014) ASK1/p38 signaling in renal tubular epithelial cells promotes renal fibrosis in the mouse obstructed kidney. Am J Physiol Ren Physiol 307(11):F1263–F1273. https://doi.org/10.1152/ajprenal.00211.2014

    Article  CAS  Google Scholar 

  79. Ying WZ, Wang PX, Sanders PW (2012) Pivotal role of apoptosis signal-regulating kinase 1 in monoclonal free light chain-mediated apoptosis. Am J Pathol 180(1):41–47. https://doi.org/10.1016/j.ajpath.2011.09.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Luciani A, Sirac C, Terryn S, Javaugue V, Prange JA, Bender S, Bonaud A, Cogne M, Aucouturier P, Ronco P, Bridoux F, Devuyst O (2016) Impaired lysosomal function underlies monoclonal light chain-associated renal Fanconi syndrome. J Am Soc Nephrol 27(7):2049–2061. https://doi.org/10.1681/ASN.2015050581

    Article  CAS  PubMed  Google Scholar 

  81. Rosenstock JL, Markowitz GS, Valeri AM, Sacchi G, Appel GB, D’Agati VD (2003) Fibrillary and immunotactoid glomerulonephritis: distinct entities with different clinical and pathologic features. Kidney Int 63(4):1450–1461. https://doi.org/10.1046/j.1523-1755.2003.00853.x

    Article  PubMed  Google Scholar 

  82. Grove P, Neale PH, Peck M, Schiller B, Haas M (1998) Monoclonal immunoglobulin G1-kappa fibrillary glomerulonephritis. Mod Pathol 11(1):103–109

    CAS  PubMed  Google Scholar 

  83. Nasr SH, Vrana JA, Dasari S, Bridoux F, Fidler ME, Kaaki S, Quellard N, Rinsant A, Goujon JM, Sethi S, Fervenza FC, Cornell LD, Said SM, McPhail ED, Herrera Hernandez LP, Grande JP, Hogan MC, Lieske JC, Leung N, Kurtin PJ, Alexander MP (2018) DNAJB9 is a specific immunohistochemical marker for fibrillary glomerulonephritis. Kidney Int Rep 3(1):56–64. https://doi.org/10.1016/j.ekir.2017.07.017

    Article  PubMed  Google Scholar 

  84. Alexander MP, Dasari S, Vrana JA, Riopel J, Valeri AM, Markowitz GS, Hever A, Bijol V, Larsen CP, Cornell LD, Fidler ME, Said SM, Sethi S, Herrera Hernandez LP, Grande JP, Erickson SB, Fervenza FC, Leung N, Kurtin PJ, Nasr SH (2018) Congophilic fibrillary glomerulonephritis: a case series. Am J Kidney Dis 72(3):325–336. https://doi.org/10.1053/j.ajkd.2018.03.017

    Article  PubMed  Google Scholar 

  85. Galesic K, Horvatic I, Tisljar M, Bulimbasic S, Bozic B, Ljubanovic DG (2011) Fibrillary glomerulonephritis and immunotactoid glomerulopathy: case reports. Lijec Vjesn 133(9–10):315–319

    PubMed  Google Scholar 

  86. Sethi S, Theis JD, Vrana JA, Fervenza FC, Sethi A, Qian Q, Quint P, Leung N, Dogan A, Nasr SH (2013) Laser microdissection and proteomic analysis of amyloidosis, cryoglobulinemic GN, fibrillary GN, and immunotactoid glomerulopathy. Clin J Am Soc Nephrol 8(6):915–921. https://doi.org/10.2215/CJN.07030712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Alpers CE, Kowalewska J (2008) Fibrillary glomerulonephritis and immunotactoid glomerulopathy. J Am Soc Nephrol 19(1):34–37. https://doi.org/10.1681/ASN.2007070757

    Article  PubMed  Google Scholar 

  88. Herrera GA, Ojemakinde KO, Turbat-Herrera EA, Gu X, Zeng X, Iskandar SS (2015) Immunotactoid glomerulopathy and cryoglobulinemic nephropathy: two entities with many similarities. A unified conceptual approach. Ultrastruct Pathol 39(4):270–280

    Article  PubMed  Google Scholar 

  89. Park SH, Ahn JY, Seo YH, Park PH, Kim KH, Song YH, Jeong JH, Lee JH (2010) A case of non-secretory myeloma with crystal-storing histiocytosis. The Korean journal of laboratory medicine 30(6):580–584. https://doi.org/10.3343/kjlm.2010.30.6.580

    Article  PubMed  Google Scholar 

  90. Fang H, Chiu A, Reichard KK (2018) Crystal-storing histiocytosis in bone marrow: a clinicopathologic study of eight cases and review of the literature. Am J Clin Pathol 149(2):148–163. https://doi.org/10.1093/ajcp/aqx150

    Article  PubMed  Google Scholar 

  91. El Hamel C, Thierry A, Trouillas P, Bridoux F, Carrion C, Quellard N, Goujon JM, Aldigier JC, Gombert JM, Cogne M, Touchard G (2010) Crystal-storing histiocytosis with renal Fanconi syndrome: pathological and molecular characteristics compared with classical myeloma-associated Fanconi syndrome. Nephrol Dial Transplant 25(9):2982–2990. https://doi.org/10.1093/ndt/gfq129

    Article  CAS  PubMed  Google Scholar 

  92. Dogan S, Barnes L, Cruz-Vetrano WP (2012) Crystal-storing histiocytosis: report of a case, review of the literature (80 cases) and a proposed classification. Head Neck Pathol 6(1):111–120. https://doi.org/10.1007/s12105-011-0326-3

    Article  PubMed  PubMed Central  Google Scholar 

  93. Sukpanichnant S, Hargrove NS, Kachintorn U, Manatsathit S, Chanchairujira T, Siritanaratkul N, Akaraviputh T, Thakerngpol K (2000) Clofazimine-induced crystal-storing histiocytosis producing chronic abdominal pain in a leprosy patient. Am J Surg Pathol 24(1):129–135

    Article  CAS  PubMed  Google Scholar 

  94. Galeano-Valle F, Diaz-Crespo FJ, Melero-Martin R, Apaza-Chavez JE, Del-Toro-Cervera J, Demelo-Rodriguez P (2019) Massive generalized crystal-storing histiocytosis associated with extracellular crystalline nephropathy: clinical, immunohistochemical, and ultrastructural studies of a unique disorder and review of the literature. CEN Case Rep 8:166–172. https://doi.org/10.1007/s13730-019-00385-5

    Article  PubMed  PubMed Central  Google Scholar 

  95. Balakrishna JP, Jaffe ES (2017) Crystal-storing histiocytosis associated with thymic extranodal marginal zone lymphoma. Blood 130(14):1683. https://doi.org/10.1182/blood-2017-07-794230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Lebeau A, Zeindl-Eberhart E, Muller EC, Muller-Hocker J, Jungblut PR, Emmerich B, Lohrs U (2002) Generalized crystal-storing histiocytosis associated with monoclonal gammopathy: molecular analysis of a disorder with rapid clinical course and review of the literature. Blood 100(5):1817–1827

    Article  CAS  PubMed  Google Scholar 

  97. Duquesne A, Werbrouck A, Fabiani B, Denoyer A, Cervera P, Verpont MC, Bender S, Piedagnel R, Brocheriou I, Ronco P, Boffa JJ, Aucouturier P, Garderet L (2013) Complete remission of monoclonal gammopathy with ocular and periorbital crystal storing histiocytosis and Fanconi syndrome. Hum Pathol 44(5):927–933. https://doi.org/10.1016/j.humpath.2012.10.012

    Article  PubMed  Google Scholar 

  98. Nasr SH, Satoskar A, Markowitz GS, Valeri AM, Appel GB, Stokes MB, Nadasdy T, D’Agati VD (2009) Proliferative glomerulonephritis with monoclonal IgG deposits. J Am Soc Nephrol 20(9):2055–2064. https://doi.org/10.1681/ASN.2009010110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Mii A, Shimizu A, Takada D, Tsuruoka S (2018) Proliferative glomerulonephritis with unusual microlamellar organized deposits related to monoclonal immunoglobulin G3 (IgG3) kappa. CEN Case Rep 7(2):320–324. https://doi.org/10.1007/s13730-018-0351-0

    Article  PubMed  PubMed Central  Google Scholar 

  100. Hemminger J, Kandarpa M, Tsai A, Nadasdy T (2016) Proliferative glomerulonephritis with monoclonal IgG1kappa deposits in a hepatitis C virus-positive patient. Am J Kidney Dis 67(4):703–708. https://doi.org/10.1053/j.ajkd.2015.08.032

    Article  PubMed  Google Scholar 

  101. Raveendran N, Beniwal P, D’Souza AV, Tanwar RS, Kimmatkar P, Agarwal D, Malhotra V (2017) Profile of glomerular diseases associated with hepatitis B and C: a single-center experience from India. Saudi J Kidney Dis Transpl 28(2):355–361. https://doi.org/10.4103/1319-2442.202761

    Article  PubMed  Google Scholar 

  102. Waldman M, Kopp JB (2007) Parvovirus B19 and the kidney. Clin J Am Soc Nephrol 2(Suppl 1):S47–S56. https://doi.org/10.2215/CJN.01060307

    Article  CAS  PubMed  Google Scholar 

  103. Fujita E, Shimizu A, Kaneko T, Masuda Y, Ishihara C, Mii A, Higo S, Kajimoto Y, Kanzaki G, Nagasaka S, Iino Y, Katayama Y, Fukuda Y (2012) Proliferative glomerulonephritis with monoclonal immunoglobulin G3kappa deposits in association with parvovirus B19 infection. Hum Pathol 43(12):2326–2333. https://doi.org/10.1016/j.humpath.2012.04.004

    Article  CAS  PubMed  Google Scholar 

  104. Perazella MA, Finkel KW, American Society of Nephrology Onco-Nephology F (2016) Paraprotein-related kidney disease: attack of the killer M proteins. Clin J Am Soc Nephrol 11(12):2256–2259. https://doi.org/10.2215/CJN.02960316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Ohashi R, Sakai Y, Otsuka T, Ohno D, Masuda Y, Murasawa T, Sato N, Shimizu A (2013) Proliferative glomerulonephritis with monoclonal IgG2kappa deposit successfully treated with steroids: a case report and review of the literature. CEN Case Rep 2(2):197–203. https://doi.org/10.1007/s13730-013-0064-3

    Article  PubMed  PubMed Central  Google Scholar 

  106. Katsuno T, Kato M, Fujita T, Tsuboi N, Hattori R, Ito Y, Maruyama S (2019) Chronological change of renal pathological findings in the proliferative glomerulonephritis with monoclonal IgG deposits considered to have recurred early after kidney transplantation. CEN Case Rep 8:151–158. https://doi.org/10.1007/s13730-019-00384-6

    Article  PubMed  PubMed Central  Google Scholar 

  107. Nasr SH, Sethi S, Cornell LD, Fidler ME, Boelkins M, Fervenza FC, Cosio FG, D’Agati VD (2011) Proliferative glomerulonephritis with monoclonal IgG deposits recurs in the allograft. Clin J Am Soc Nephrol 6(1):122–132. https://doi.org/10.2215/CJN.05750710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was funded by the Supporting Project for the Foregoers of Main Disciplines of Jiangxi Province (No. 20162BCB22023), the “5511” Innovative Drivers for Talent Teams of Jiangxi Province (No. 20165BCB18018), and the Nature Science Foundation of Jiangxi Province (No. 20181BAB205016).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gaosi Xu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zuo, C., Zhu, Y. & Xu, G. An update to the pathogenesis for monoclonal gammopathy of renal significance. Ann Hematol 99, 703–714 (2020). https://doi.org/10.1007/s00277-020-03971-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-020-03971-1

Keywords

Navigation