Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1 (5-Year IF – 2.0)
Journal Citation Indicator (JCI) (2023) – 0.4
Scopus CiteScore – 3.7 (CiteScore Tracker – 4.2)
Index Copernicus  – 171.00; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2011, vol. 20, nr 5, September-October, p. 647–652

Publication type: review article

Language: English

AL Amyloidosis (Amyloidosis Antibody Light). Part 1. Definition, Classification, Amyloid Structure, Development and Etiopathogenesis of AL Amyloidosis

Amyloidoza AL (amyloidosis antibody light). Część I. Definicja, podział, budowa i rozwój amyloidu, etiopatogeneza amyloidozy AL

Lidia Usnarska-Zubkiewicz1,, Jadwiga Hołojda2,, Kazimierz Kuliczkowski1,

1 Departament of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Poland

2 Hematology Department of District Specialist Hospital of Legnica, Poland

Abstract

Amyloidosis is an inherited or acquired systemic storage disease in which a pathologic, amorphous substance produced as a result of abnormal protein metabolism and resistant to proteolysis is deposited in the extracellular space of various tissues (intracellular deposits occur rarely). This leads to the destruction of normal tissue architecture and disturbs its function. The development of amyloidosis is associated with the transformation of the α-spiral conformation of fibrous protein into a stratified, parallel, folded spatial β-conformation. The transition of the fibrous proteins conformation and their tissue localization causes resistance of the fibers to proteolytic processes as a result of a limited access of the protein converting enzymes. In this paper we show the actual classification of amyloidosis and up-to-date knowledge about the amyloid structure, development and etiopathogenesis of AL amyloidosis.

Streszczenie

Amyloidoza (skrobiawica) jest wrodzoną lub nabytą układową chorobą spichrzeniową, w przebiegu której dochodzi do gromadzenia się w przestrzeni pozakomórkowej różnych tkanek (rzadko wewnątrzkomórkowo), patologicznej, amorficznej substancji, która powstaje na skutek nieprawidłowego metabolizmu białek i jest oporna na proteolizę. Prowadzi to do zniszczenia normalnej architektoniki tkanek i zakłócenia ich funkcji. Rozwój amyloidozy jest związany z przekształceniem α-spiralnej konformacji włókien białkowych w warstwową, równoległą, pofałdowaną, przestrzenną β-konformację. Zmiana konformacji włókien białkowych i ich tkankowe umiejscowienie powoduje oporność włókien na procesy proteolityczne w wyniku ograniczonego dostępu enzymów rozkładających białka. W pracy przedstawiono aktualny podział amyloidozy oraz obecny stan wiedzy na temat rozwoju, budowy i etiopatogenezy amyloidozy z łańcuchów lekkich.

Key words

amyloidosis AL, classification, amyloid structure, etiopathogenesis

Słowa kluczowe

amyloidoza AL, klasyfikacja, struktura amyloidu, etiopatogeneza

References (33)

  1. Merlini G, Belloti V: Molecular mechanisms of amyloidosis. N Engl J Med 2003, 349, 583–596.
  2. Merlini G, Seldin DC, Gertz MA: Amyloidosis: pathogenesis and new therapeutic options. J Clin Oncol 2011 10, 29, 1924–1933.
  3. Kyle RA, Gertz MA: Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol 1995, 32, 45–59.
  4. Westermark P, Benson MD, Buxbaum JN, Cohen AS, Frangione B, Ikeda S, Masters CL, Merlini G, Saraiva MJ, Sipe JD: Amyloid fibril protein nomenclature – 2002. Amyloid 2002, 9, 197–200.
  5. Saeger W, Röcken C: Amyloid. Mikroskopischer Nachweis, Klassifikation und klinischer Bezug. Pathologe 1998, 19, 345–354 Springer-Verlag.
  6. Abraham RS, Katzmann JA, Clark RJ, Bradwell AR, Kyle RA, Gertz MA: Quantitative analysis of serum free light chains. A new marker for the diagnostic evaluation of primary systemic amyloidosis. Am J Clin Pathol 2003, 119, 274–278.
  7. Benditt EP, Eriksen N, Hermodson MA, Ericsson LH: The major proteins of human and monkey amyloid substance: common properties including unusual N-terminal amino acid sequences. FEBS Lett 1971, 19, 169–173.
  8. Schonland S: Fortschritte in der Diagnostik und Therapie der Amyloidosen. Deutsches Ärzteblatt 2006, 103/Heft 34–35/28.
  9. Jurczyszyn A, Skotnicki AB: Postępy w badaniach nad molekularną patogenezą amyloidozy oraz implikacje kliniczne. Adv Clin Exp Med 2004, 13, 669–676.
  10. Solomon A: Light chains of human immunoglobulins. Meth Enzymol 1985, 116, 101–121.
  11. Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, Kyle RA.: Serum reference intervals and diagnostic ranges for the free κ and free λ immunoglobulin light chains. Relative sensitivity for detection of monoclonal light chains. Clin Chem 2002, 48, 1437–1444.
  12. Solomon A, Frangione B, Franklin EC.: Bence Jones proteins and light chains of immunoglobulins: preferential association of the V lambda VI subgroup of human light chains with amyloidosis AL (lambda). J Clin Invest 1982, 70, 453–460.
  13. Ionescu-Zanetti C, Khurana R, Gillespie JR, Petrick JS, Trabachino LC, Minert LJ, Carter SA, Fink AL: Monitoring the assembly of Ig light-chain amyloid fibrils by atomic force microscopy. Proc Natl Acad Sci USA 1999, 96, 13175–13179.
  14. Comenzo RL, Zhang Y, Martinez C, Osman K, Herrera GA: The tropism of organ involvement in primary systemic amyloidosis: contributions of Ig V(L) germ line gene use and clonal plasma cell burden. Blood 2001, 98, 714–720.
  15. Abraham RS, Geyer SM, Price-Troska TL, Allmer C, Kyle RA, Gertz MA, Fonseca R: Immunoglobulin light chain variable(V)region genes influence clinical presentation and outcome in light chain-associated amyloidosis (AL). Blood 2003, 101, 3801–3808.
  16. Perfetti V, Casarini S, Palladini G, Vignarelli MC, Klersy C, Diegoli M, Ascari E, Merlini G: Analysis of V lambda-J lambda expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r (lambda III) as a new amyloid-associated germinal gene segment. Blood 2002, 100, 948–953.
  17. Sipe JD: Cohen: History of the amyloid fibril. J Struct Biol 2000, 130, 88–98.
  18. Stevens FJ, Kiselevsky R: Immunoglobulin light chains, glycosaminoglycans and amyloid. Cell Mol Life Sci 2000, 57, 441–449.
  19. Ren R, Hong Z, Gong H, Laporte K, Skinner M, Seldin DC, Costello CE, Connors LH, Trinkaus-Randall V: Role of glycosaminoglycan sulfation in the formation of immunoglobulin light chain amyloid oligomers and fibrils. J Biol Chem 2010, 285, 37672–37682.
  20. Bellotti V, Merlini G Toward: Understanding the molecular pathogenesis of monoclonal immunoglobulin Lightchain deposition. Nephrol Dial Transplant 1996, 11, 9, 1708–1711.
  21. Buxbaum J: The genetics of the amyloidosis, interactions with immunity and inflammation. Genes and immunity 2006, 7, 439–449.
  22. Verdone G, Corazza A, Viglino P, Pettirossi F, Giorgetti S, Mangione P, Andreola A, Stoppini M, Bellotti V, Esposito G: The solution structure of human beta2-microglobulin reveals the prodromes of its amyloid transition. Protein Sci 2002, 11, 487–499.
  23. Hardy J, Selkoe DJ: The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 2002, 297, 353–356.
  24. Comenzo RL, Aally J, Kica G, Murray J, Ericsson T, Skinner M: Clonal immunoglobulin light chain variable region germ line gene use in AL amyloidosis: association with dominant amyloid-related organ involvement and survival after stem cell transplantation. Br J Haematol 1999, 106, 744–751.
  25. Raffen R, Dieckman LJ, Szpunar M, Wunschl C, Pokkulari PR, Dave P: Physicochemical consequences of amino acid variations that contribute to fibril formation by immunoglobulin light chains. Protein Sci 1999, 8, 509–517.
  26. Hayman SR, Bailey RJ, Jalal SM, Ahmann GJ, Dispenzieri A, Gertz MA, Greipp PR, Kyle RA, Lacy MQ, Rajkumar SV, Witzig TE, Lust JA, Fonseca R: Translocations involving the immunoglobulin heavy chain locus are possible early genetic events in patients with primary systemic amyloidosis. Blood 2001, 98, 2266–2268.
  27. Harrison CJ, Mazzullo H, Ross FM, Cheung KL, Gerrard G, Harewood L, Mehta A, Lachmann HJ, Hawkins PN, Orchard KH: Translocationes of 14q32 and deletions of 13q14 are common chromosomal abnormalities in systemiec amyloidosis. Br J Haematol 2002, 117, 427–435.
  28. Bryce AH, Ketterling RP, Gertz MA, Lacy M, Knudson RA, Zeldenrust S, Kumar S, Hayman S, Buadi F, Kyle RA, Greipp PR, Lust JA, Russell S, Rajkumar SV, Fonseca R, Dispenzieri A: Translocation t(11,14) and survival of patients with light chain (AL) amyloidosis. Haematologica 2009, 94, 380–386.
  29. Poshusta TL, Sikkink LA, Leung N, Clark RJ, Dispenzieri A, Ramirez-Alvarado M: Mutations in specific structural regions of immunoglobulin light chains are associated with free light chain levels in patients with AL amyloidosis. PLoS One 2009, 4, e5169.
  30. Solomon A, Macy SD, Wooliver C, Weiss DT, Westermark P: Splenic plasma cells can serve as a source of amyloidogenic light chains. Blood 2009, 12, 113, 1501–1503.
  31. 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, 440–451.
  32. Iwahashi N, Tame E, Nagasaka T, Furuta M, Nagashima H, Nimura Y: Massive hemorrhage and pseudoobstruction of the small intestine caused by primary AL amyloidosis associated with gastric cancer: report of a case. Surg Today 2004, 34, 871–874
  33. Palladini G, Lavatelli F, Russo P, Perlini S, Perfetti V, Bosoni T, Obici L, Bradwell AR, D’Eril GM, Fogari R, Moratti R, Merlini G: Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously association with improvement of survival in AL. Blood 2006, 107, 3854–3858.
© Wroclaw Medical University