Skip to main content

Advertisement

SpringerLink
Log in

Co-deposition of amyloidogenic immunoglobulin light and heavy chains in localized pulmonary amyloidosis

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Localized pulmonary amyloidosis is a rare condition whose pathogenesis is insufficiently understood. In the present study, we report a case of localized pulmonary amyloidosis associated with lung-restricted lymphoplasmacytoid lymphoma, monoclonal for immunoglobulin (Ig) G lambda (λ). Biochemical microtechniques have been applied for extraction, purification, and characterization of amyloid proteins. Surprisingly, chemical analysis of these proteins revealed a not-previously-described case of combined deposits containing Ig fragments of gamma heavy chain (variable domain) and λ light chain (constant domain). In view of the absence of circulating monoclonal Ig, this case supports the hypothesis that localized amyloid is formed by local plasmacytoid cells.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Brohee D, Cauchie P, Delval L, Govaerts D, Neve P, Piro P (2002) Frequent discordance of the light-chain isotypes expressed by serum monoclonal components and leukaemic B-cells. Clin Lab Haematol 24:151–154

    Article  PubMed  CAS  Google Scholar 

  2. Buxbaum JN (2001) Abnormal immunoglobulin synthesis in monoclonal light chain and light and heavy chain deposition disease. Amyloid 8:84–93

    PubMed  CAS  Google Scholar 

  3. Copeland JN, Kouides PA, Grieff M, Nadasdy T (2003) Metachronous development of nonamyloidogenic λ light chain deposition disease and IgG heavy chain amyloidosis. Am J Surg Pathol 27:1477–1482

    Article  PubMed  Google Scholar 

  4. Davis CJ, Butchart, Gibbs AR (1991) Nodular pulmonary amyloidosis occurring in association with pulmonary lymphoma. Thorax 46:217–218

    Article  PubMed  CAS  Google Scholar 

  5. Ditzel HJ, Barbas SM, Barbas CF III, Burton DR (1994) The nature of the autoimmune antibody repertoire in human immunodeficiency virus type λ infection. Proc Natl Acad Sci U S A 91:3710–3714

    Article  PubMed  CAS  Google Scholar 

  6. Envig JP, Olsen KE, Gislefoss RE, Sletten K, Wahlstrom O, Westermark P (1998) Constant region of a κIII immunoglobulin light chain as a major AL-amyloid protein. Scand J Immunol 48:92–98

    Article  PubMed  Google Scholar 

  7. Eulitz M, Weiss DT, Solomon A (1990) Immunoglobulin heavy-chain-associated amyloidosis. Proc Natl Acad Sci U S A 87:6542–6546

    Article  PubMed  CAS  Google Scholar 

  8. Hamidi Asl K, Liepnieks JJ, Nakamura M, Benson MD (1999) Organ-specific (localized) synthesis of Ig light chain amyloid. J Immunol 162:5556–5560

    PubMed  CAS  Google Scholar 

  9. Howard ME, Ireton J, Daniels F, Langton D, Manolitsas ND, Fogarty P, McDonald CE (2001) Pulmonary presentations of amyloidosis. Respirology 6:61–64

    Article  PubMed  CAS  Google Scholar 

  10. Hui AN, Koss MN, Hochholzer L, Wehunt WD (1986) Amyloidosis presenting in the lower respiratory tract. Arch Pathol Lab Med 110:212–218

    PubMed  CAS  Google Scholar 

  11. Ihling C, Weirich G, Gaa A, Schaefer HE (1996) Amyloid tumors of the lung—an immunocytoma? Pathol Res Pract 192:446–452

    PubMed  CAS  Google Scholar 

  12. Kaplan B, Yakar S, Kumar A, Pras M, Gallo G (1997) Immunochemical characterization of amyloid in diagnostic biopsy tissues. Amyloid 4:80–86

    Google Scholar 

  13. Kaplan B, Hrncic R, Murphy CL, Gallo G, Weiss DT, Solomon A (1999) Microextraction and purification techniques applicable to the characterization of amyloid proteins in minute amounts of tissue. Methods Enzymol 309:67–81

    Article  PubMed  CAS  Google Scholar 

  14. Kaplan B, Murphy CL, Ratner V, Pras M, Weiss D, Solomon A (2001) Micro-method to isolate and purify amyloid proteins for chemical characterization. Amyloid 8:22–29

    PubMed  CAS  Google Scholar 

  15. Kaplan B, Shtrasburg S, Pras M (2003) Micropurification techniques in analysis of amyloid proteins. J Clin Pathol 56:86–90

    Article  PubMed  CAS  Google Scholar 

  16. Kaplan B, Martin BM, Livneh A, Pras M, Gallo G (2004) Biochemical subtyping of amyloid in formalin-fixed tissue samples confirms and supplements immunohistochemical data. Am J Clin Pathol 121:794–800

    Article  PubMed  CAS  Google Scholar 

  17. Khoor A, Myers JL, Tazelaar HD, Kurtin PJ (2004) Amyloid-like pulmonary nodules, including localized light-chain deposition. Am J Clin Pathol 121:200–204

    Article  PubMed  Google Scholar 

  18. Lim JK, Lacy MQ, Kyle RA, Gertz MA (2001) Pulmonary marginal zone lymphoma of MALT type as a cause of localized pulmonary amyloidosis. J Clin Pathol 54:642–646

    Article  PubMed  CAS  Google Scholar 

  19. Lolin YI, Chow J, Wickman NW (1996) Monoclonal gammopathy of unknown significance and malignant paraproteinemia in Hong Kong. Am J Clin Pathol 106:449–456

    PubMed  CAS  Google Scholar 

  20. Mai HL, Sheikh-Hamad D, Herrera GA, Gu X, Truong LD (2003) Immunoglobulin heavy chain can be amyloidogenic: morphological characterization including immunoelectron microscopy. Am J Surg Pathol 27:541–545

    Article  PubMed  Google Scholar 

  21. Miura K, Shirasawa H (1993) Lambda III subgroup immunoglobulin light chains are precursor proteins of nodular pulmonary amyloidosis. Am J Clin Pathol 100:561–566

    PubMed  CAS  Google Scholar 

  22. Moriyama E, Yokose T, Kodama T, Matsuno Y, Hojo F, Takahasshi K, Nagai K, Nishiwaki Y, Ochiai A (2000) Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue in the thymus of a patient with pulmonary amyloid nodules. Jpn J Clin Oncol 30:349–353

    Article  PubMed  CAS  Google Scholar 

  23. Murphy CL, Eulitz M, Hrncic R, Sletten K, Westermark P, Williams T, Macy SD, Wooliver C, Wall J, Weiss DT, Solomon DT, Solomon A (2001) Chemical typing of amyloid proteins contained in formalin-fixed paraffin-embedded biopsy specimens. Am J Clin Pathol 116:135–142

    Article  PubMed  CAS  Google Scholar 

  24. Olsen KR, Sletten K, Westermark P (1998) Fragments of the constant region of immunoglobulin light chains are constituents of AL-amyloid proteins. Biochem Biophys Res Commun 251:642–647

    Article  PubMed  CAS  Google Scholar 

  25. Page DL, Isersky CH, Harada M, Glenner GG (1972) Immunoglobulin origin of localized nodular pulmonary amyloidosis. Res Exp Med 159:75–86

    Article  CAS  Google Scholar 

  26. Rodilla Sala R, Kratzin HD, Pick AI, Hilschmann N (1991) Biclonality in amyloidosis patient MAL: one clone producing an amyloidogenic, the other a non-amyloidogenic kappa λ-chain. In: Natvig JB, Forre O, Husby G, Husebekk A, Skogen B, Sletten K, Westermark P (eds) Amyloid and amyloidosis 1990. Kluwer, Dordrecht, pp 161–164

    Google Scholar 

  27. Rostango A, Frizzera G, Ylagan L, Kumar A, Ghiso J, Gallo G (2002) Tumoral non-amyloidotic monoclonal immunoglobulin light chain deposits (“aggregoma”): presenting feature of B-cell dyscrasia in three cases with immunohistochemical and biochemical analyses. Br J Haematol 119:62–69

    Article  PubMed  Google Scholar 

  28. Sahota SS, Garand R, Bataille R, Smith AJ, Stevenson FK (1998) VH gene analysis of clonality related IgM and IgG from human lymphoplasmacytoid B-cell tumors with chronic lymphocytic leukemia features and high serum monoclonal IgG. Blood 91:238–243

    PubMed  CAS  Google Scholar 

  29. Sklar J, Cleary ML, Thielemans K, Gralow J, Warnke R, Levy R (1984) Biclonal B-cell lymphoma. N Engl J Med 311:20–27

    Article  PubMed  CAS  Google Scholar 

  30. Solomon A, Weiss DT, Murphy C (1994) Primary amyloidosis associated with a novel heavy-chain fragment (AH amyloidosis). Am J Hematol 45:171–176

    Article  PubMed  CAS  Google Scholar 

  31. Solomon A, Weiss D, Murphy CL, Hrncic R, Wall JS, Schell M (1998) Light chain-associated amyloid deposits comprised of a novel κ constant domain. Proc Natl Acad Sci U S A 95:9547–9551

    Article  PubMed  CAS  Google Scholar 

  32. Stokes MB, Jagirdar J, Burshstin O, Kornacki S, Kumar A, Gallo G (1997) Nodular pulmonary immunoglobulin light chain deposits with coexistent amyloid and nonamyloid features in an HIV-infected patient. Mod Path 10:1059–1065

    CAS  Google Scholar 

  33. Tan SY, Murdoch IE, Sullivan TJ, Wright JE, Truong O, Hsuan JJ, Hawkins PN, Pepys MB (1994) Primary localized orbital amyloidosis composed of the immunoglobulin γ heavy chain CH3 domain. Clin Sci 87:487–491

    PubMed  CAS  Google Scholar 

  34. Wally J, Kica G, Zhang Y, Ericsson T, Benson MD, Liepnieks JJ, Murray J, Skinner M, Comenzo RL (1999) Identification of a novel substitution in the constant region of a gene coding for an amyloidogenic κ1 light chain. Biochim Biophys Acta 1454:49–56

    PubMed  CAS  Google Scholar 

  35. Wieker K, Rocken C, Koenigsmann M, Roessner A, Franke A (2002) Pulmonary low-grade MALT-lymphoma associated with localized pulmonary amyloidosis. Amyloid 9:190–193

    PubMed  Google Scholar 

  36. Yazaki M, Fushimi T, Tokuda T, Kametani F, Yamamoto K, Matsuda M, Shimojo H, Hosshii Y, Higuchi K, Ikeda S (2004) A patient with severe renal amyloidosis associated with an immunoglobulin γ-heavy chain fragment. Am J Kidney Dis 43:E23–E28

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer, 52621, Israel

    Batia Kaplan & Mordechai Pras

  2. Sackler School of Medicine, Tel-Aviv University, Tel Hashomer, Israel

    Batia Kaplan, Rivka Gal & Mordechai Pras

  3. Laboratory of Neurotoxicology, National Institute of Mental Health, Bethesda, MD, USA

    Brian M. Martin

  4. Department of Pathology, Beilinson Campus, Rabin Medical Center, Petah Tiqva, Israel

    Olga Boykov & Itzhak Shechtman

  5. Department of Pathology, Golda Campus, Rabin Medical Center, Petah Tiqva, Israel

    Rivka Gal

  6. Department of Thoracic Surgery, Beilinson Campus, Rabin Medical Center, Petah Tiqva, Israel

    Milton Saute

  7. Pulmonary Institute, Beilinson Campus, Rabin Medical Center, Petah Tiqva, Israel

    Mordechai R. Kramer

Authors
  1. Batia Kaplan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian M. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olga Boykov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rivka Gal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mordechai Pras
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Itzhak Shechtman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Milton Saute
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mordechai R. Kramer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Batia Kaplan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kaplan, B., Martin, B.M., Boykov, O. et al. Co-deposition of amyloidogenic immunoglobulin light and heavy chains in localized pulmonary amyloidosis. Virchows Arch 447, 756–761 (2005). https://doi.org/10.1007/s00428-005-0009-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-005-0009-0

Keywords

Search

Navigation