Amyloidoses are a spectrum of disorders caused by abnormal folding and extracellular deposition of proteins. The deposits lead to tissue damage and organ dysfunction, particularly in the heart, kidneys, and nerves. There are at least 30 different proteins that can cause amyloidosis. The clinical management depends entirely on the type of protein deposited, and thus on the underlying pathogenesis, and often requires high-risk therapeutic intervention. Application of mass spectrometry–based proteomic technologies for analysis of amyloid plaques has transformed the way amyloidosis is diagnosed and classified. Proteomic assays have been extensively used for clinical management of patients with amyloidosis, providing unprecedented diagnostic and biological information. They have shed light on the pathogenesis of different amyloid types and have led to identification of numerous new amyloid types, including ALECT2 amyloidosis, which is now recognized as one of the most common causes of systemic amyloidosis in North America.


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Literature Cited

  1. Merlini G, Bellotti V. 1.  2003. Molecular mechanisms of amyloidosis. N. Engl. J. Med. 349:583–96 [Google Scholar]
  2. Chiti F, Dobson CM. 2.  2006. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 75:333–66 [Google Scholar]
  3. Knowles TP, Vendruscolo M, Dobson CM. 3.  2014. The amyloid state and its association with protein misfolding diseases. Nat. Rev. Mol. Cell Biol. 15:384–96 [Google Scholar]
  4. Toyama BH, Weissman JS. 4.  2011. Amyloid structure: conformational diversity and consequences. Annu. Rev. Biochem. 80:557–85 [Google Scholar]
  5. Westermark GT, Fandrich M, Westermark P. 5.  2015. AA amyloidosis: pathogenesis and targeted therapy. Annu. Rev. Pathol. 10:321–44 [Google Scholar]
  6. Sipe JD, Benson MD, Buxbaum JN, Ikeda S, Merlini G. 6.  et al. 2014. Nomenclature 2014: amyloid fibril proteins and clinical classification of the amyloidosis. Amyloid 21:221–24 [Google Scholar]
  7. Rodriguez FJ, Picken MM, Lee JM. 7.  2015. Amyloid deposition in the central nervous system. See Ref. 25 121–31
  8. Vinters HV. 8.  2015. Emerging concepts in Alzheimer's disease. Annu. Rev. Pathol. 10:291–319 [Google Scholar]
  9. Westermark P, Sletten K. 9.  1982. A serum AA-like protein as a common constituent of secondary amyloid fibrils. Clin. Exp. Immunol. 49:725–31 [Google Scholar]
  10. Westermark GT, Westermark P. 10.  2009. Serum amyloid A and protein AA: molecular mechanisms of a transmissible amyloidosis. FEBS Lett 583:2685–90 [Google Scholar]
  11. Chen CD, Huff ME, Matteson J, Page L, Phillips R. 11.  et al. 2001. Furin initiates gelsolin familial amyloidosis in the Golgi through a defect in Ca2+ stabilization. EMBO J 20:6277–87 [Google Scholar]
  12. Kim SH, Wang R, Gordon DJ, Bass J, Steiner DF. 12.  et al. 1999. Furin mediates enhanced production of fibrillogenic ABri peptides in familial British dementia. Nat. Neurosci. 2:984–88 [Google Scholar]
  13. Haggqvist B, Naslund J, Sletten K, Westermark GT, Mucchiano G. 13.  et al. 1999. Medin: an integral fragment of aortic smooth muscle cell-produced lactadherin forms the most common human amyloid. PNAS 96:8669–74 [Google Scholar]
  14. Abrahamson M, Grubb A. 14.  1994. Increased body temperature accelerates aggregation of the Leu-68→Gln mutant cystatin C, the amyloid-forming protein in hereditary cystatin C amyloid angiopathy. PNAS 91:1416–20 [Google Scholar]
  15. Pepys MB, Hawkins PN, Booth DR, Vigushin DM, Tennent GA. 15.  et al. 1993. Human lysozyme gene mutations cause hereditary systemic amyloidosis. Nature 362:553–57 [Google Scholar]
  16. Benson MD. 16.  2015. The hereditary amyloidoses. See Ref. 25 65–80
  17. Comenzo RL, Wally J, Kica G, Murray J, Ericsson T. 17.  et al. 1999. Clonal immunoglobulin light chain variable region germline gene use in AL amyloidosis: association with dominant amyloid-related organ involvement and survival after stem cell transplantation. Br. J. Haematol. 106:744–51 [Google Scholar]
  18. Nelson SR, Lyon M, Gallagher JT, Johnson EA, Pepys MB. 18.  1991. Isolation and characterization of the integral glycosaminoglycan constituents of human amyloid A and monoclonal light-chain amyloid fibrils. Biochem. J. 275:Part 167–73 [Google Scholar]
  19. Pepys MB, Rademacher TW, Amatayakul-Chantler S, Williams P, Noble GE. 19.  et al. 1994. Human serum amyloid P component is an invariant constituent of amyloid deposits and has a uniquely homogeneous glycostructure. PNAS 91:5602–6 [Google Scholar]
  20. Kumar SK, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK. 20.  et al. 2011. Changes in serum-free light chain rather than intact monoclonal immunoglobulin levels predicts outcome following therapy in primary amyloidosis. Am. J. Hematol. 86:251–55 [Google Scholar]
  21. Merlini G, Seldin DC, Gertz MA. 21.  2011. Amyloidosis: pathogenesis and new therapeutic options. J. Clin. Oncol. 29:1924–33 [Google Scholar]
  22. Holmgren G, Steen L, Suhr O, Ericzon B-G, Groth C-G. 22.  et al. 1993. Clinical improvement and amyloid regression after liver transplantation in hereditary transthyretin amyloidosis. Lancet 341:1113–16 [Google Scholar]
  23. Gertz MA, Benson MD, Dyck PJ, Grogan M, Coelho T. 23.  et al. 2015. Diagnosis, prognosis, and therapy of transthyretin amyloidosis. J. Am. Coll. Cardiol. 66:2451–66 [Google Scholar]
  24. Palladini G, Merlini G. 24.  2016. What is new in diagnosis and management of light chain amyloidosis?. Blood 128:159–68 [Google Scholar]
  25. Picken MM, Herrera GA, Dogan A. 25.  2015. Amyloid and Related Disorders. Surgical Pathology and Clinical Correlations New York: Humana, 2nd ed.. [Google Scholar]
  26. Gertz MA, Li CY, Shirahama T, Kyle RA. 26.  1988. Utility of subcutaneous fat aspiration for the diagnosis of systemic amyloidosis (immunoglobulin light chain). Arch. Intern. Med. 148:929–33 [Google Scholar]
  27. Andrews TR, Colon-Otero G, Calamia KT, Menke DM, Boylan KB, Kyle RA. 27.  2002. Utility of subcutaneous fat aspiration for diagnosing amyloidosis in patients with isolated peripheral neuropathy. Mayo Clin. Proc. 77:1287–90 [Google Scholar]
  28. van Gameren II, Hazenberg BPC, Bijzet J, van Rijswijk MH. 28.  2006. Diagnostic accuracy of subcutaneous abdominal fat tissue aspiration for detecting systemic amyloidosis and its utility in clinical practice. Arthritis Rheum 54:2015–21 [Google Scholar]
  29. Westermark P, Davey E, Lindbom K, Enqvist S. 29.  2006. Subcutaneous fat tissue for diagnosis and studies of systemic amyloidosis. Acta Histochem 108:209–13 [Google Scholar]
  30. Hazenberg BPC, Bijzet J, Limburg PC, Skinner M, Hawkins PN. 30.  et al. 2007. Diagnostic performance of amyloid A protein quantification in fat tissue of patients with clinical AA amyloidosis. Amyloid 14:133–40 [Google Scholar]
  31. Howie AJ. 31.  2015. Diagnosis of amyloid using Congo red. See Ref. 25 197–212
  32. Howie AJ, Brewer DB. 32.  2009. Optical properties of amyloid stained by Congo red: history and mechanisms. Micron 40:285–301 [Google Scholar]
  33. Feurle GE, Linke RP, Kuhn E, Wagner A. 33.  1984. Clinical value of immunohistochemistry with AF-antibody in the diagnosis of familial amyloid neuropathy. J. Neurol. 231:237–43 [Google Scholar]
  34. Janssen S, Elema JD, van Rijswijk MH, Limburg PC, Meijer S, Mandema E. 34.  1985. Classification of amyloidosis: immunohistochemistry versus the potassium permanganate method in differentiating AA from AL amyloidosis. Appl. Pathol. 3:29–38 [Google Scholar]
  35. Olson LJ, Gertz MA, Edwards WD, Li CY, Pellikka PA. 35.  et al. 1987. Senile cardiac amyloidosis with myocardial dysfunction. Diagnosis by endomyocardial biopsy and immunohistochemistry. N. Engl. J. Med. 317:738–42 [Google Scholar]
  36. Horn U, Goebel HH, Storkel S, Bohl J, Thomas E. 36.  et al. 1991. Immunohistochemistry of amyloid-related neuropathies. Clin. Neuropathol. 10:237–43 [Google Scholar]
  37. Li K, Kyle RA, Dyck PJ. 37.  1992. Immunohistochemical characterization of amyloid proteins in sural nerves and clinical associations in amyloid neuropathy. Am. J. Pathol. 141:217–26 [Google Scholar]
  38. Hoshii Y, Takahashi M, Ishihara T, Uchino F. 38.  1994. Immunohistochemical classification of 140 autopsy cases with systemic amyloidosis. Pathol. Int. 44:352–58 [Google Scholar]
  39. Swan N, Skinner M, O'Hara CJ. 39.  2003. Bone marrow core biopsy specimens in AL (primary) amyloidosis. A morphologic and immunohistochemical study of 100 cases. Am. J. Clin. Pathol. 120:610–16 [Google Scholar]
  40. Kebbel A, Rocken C. 40.  2006. Immunohistochemical classification of amyloid in surgical pathology revisited. Am. J. Surg. Pathol. 30:673–83 [Google Scholar]
  41. Picken MM, Herrera GA. 41.  2007. The burden of “sticky” amyloid: typing challenges. Arch. Pathol. Lab. Med. 131:850–51 [Google Scholar]
  42. Linke RP, Oos R, Wiegel NM, Nathrath WB. 42.  2006. Classification of amyloidosis: misdiagnosing by way of incomplete immunohistochemistry and how to prevent it. Acta Histochem 108:197–208 [Google Scholar]
  43. Solomon A, Murphy CL, Westermark P. 43.  2008. Unreliability of immunohistochemistry for typing amyloid deposits. Arch. Pathol. Lab. Med. 132:14–15 [Google Scholar]
  44. Linke RP. 44.  2011. Classification of amyloid on fixed tissue sections for routine use by validated immunohistochemistry. Amyloid 18:Suppl. 167–70 [Google Scholar]
  45. Westermark P. 45.  2011. Amyloid diagnosis, subcutaneous adipose tissue, immunohistochemistry and mass spectrometry. Amyloid 18:175–76 [Google Scholar]
  46. Linke RP. 46.  2012. On typing amyloidosis using immunohistochemistry. Detailled illustrations, review and a note on mass spectrometry. Prog. Histochem. Cytochem. 47:61–132 [Google Scholar]
  47. Gilbertson JA, Theis JD, Vrana JA, Lachmann H, Wechalekar A. 47.  et al. 2015. A comparison of immunohistochemistry and mass spectrometry for determining the amyloid fibril protein from formalin-fixed biopsy tissue. J. Clin. Pathol. 68:314–17 [Google Scholar]
  48. Murphy CL, Wang S, Williams T, Weiss DT, Solomon A. 48.  2006. Characterization of systemic amyloid deposits by mass spectrometry. Methods Enzymol 412:48–62 [Google Scholar]
  49. Solomon A, Murphy CL, Kestler D, Coriu D, Weiss DT. 49.  et al. 2006. Amyloid contained in the knee joint meniscus is formed from apolipoprotein A-I. Arthritis Rheum 54:3545–50 [Google Scholar]
  50. Vrana JA, Gamez JD, Madden BJ, Theis JD, Bergen HR, Dogan A. 50.  2009. Classification of amyloidosis by laser microdissection and mass spectrometry–based proteomic analysis in clinical biopsy specimens. Blood 114:4957–59 [Google Scholar]
  51. Lavatelli F, Brambilla F, Valentini V, Rognoni P, Casarini S. 51.  et al. 2011. A novel approach for the purification and proteomic analysis of pathogenic immunoglobulin free light chains from serum. Biochim. Biophys. Acta 1814:409–19 [Google Scholar]
  52. Lavatelli F, Vrana JA. 52.  2011. Proteomic typing of amyloid deposits in systemic amyloidoses. Amyloid 18:177–82 [Google Scholar]
  53. Brambilla F, Lavatelli F, Di Silvestre D, Valentini V, Rossi R. 53.  et al. 2012. Reliable typing of systemic amyloidoses through proteomic analysis of subcutaneous adipose tissue. Blood 119:1844–47 [Google Scholar]
  54. Vrana JA, Theis JD, Dasari S, Mereuta OM, Dispenzieri A. 54.  et al. 2014. Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics. Haematologica 99:1239–47 [Google Scholar]
  55. Meissner F, Mann M. 55.  2014. Quantitative shotgun proteomics: considerations for a high-quality workflow in immunology. Nat. Immunol. 15:112–17 [Google Scholar]
  56. Lim MS, Elenitoba-Johnson KS. 56.  2004. Proteomics in pathology research. Lab. Investig. 84:1227–44 [Google Scholar]
  57. Theis JD, Dasari S, Vrana JA, Kurtin PJ, Dogan A. 57.  2013. Shotgun-proteomics-based clinical testing for diagnosis and classification of amyloidosis. J. Mass Spectrom. 48:1067–77 [Google Scholar]
  58. Hood BL, Conrads TP, Veenstra TD. 58.  2006. Mass spectrometric analysis of formalin-fixed paraffin-embedded tissue: unlocking the proteome within. Proteomics 6:4106–14 [Google Scholar]
  59. Prieto DA, Hood BL, Darfler MM, Guiel TG, Lucas DA. 59.  et al. 2005. Liquid TissueTM: proteomic profiling of formalin-fixed tissues. Biotechniques 38:S32–35 [Google Scholar]
  60. Dasari S, Theis JD, Vrana JA, Zenka RM, Zimmermann MT. 60.  et al. 2014. Clinical proteome informatics workbench detects pathogenic mutations in hereditary amyloidoses. J. Proteome Res. 13:2352–58 [Google Scholar]
  61. Murphy CL, Eulitz M, Hrncic R, Sletten K, Westermark P. 61.  et al. 2001. Chemical typing of amyloid protein contained in formalin-fixed paraffin-embedded biopsy specimens. Am. J. Clin. Pathol. 116:135–42 [Google Scholar]
  62. Kaplan B, Martin BM, Livneh A, Pras M, Gallo GR. 62.  2004. Biochemical subtyping of amyloid in formalin-fixed tissue samples confirms and supplements immunohistologic data. Am. J. Clin. Pathol. 121:794–800 [Google Scholar]
  63. Rodriguez FJ, Gamez JD, Vrana JA, Theis JD, Giannini C. 63.  et al. 2008. Immunoglobulin derived depositions in the nervous system: novel mass spectrometry application for protein characterization in formalin-fixed tissues. Lab. Investig. 88:1024–37 [Google Scholar]
  64. Payto D, Heideloff C, Wang S. 64.  2016. Sensitive, simple, and robust nano-liquid chromatography-mass spectrometry method for amyloid protein subtyping. Clinical Applications of Mass Spectrometry in Biomolecular Analysis: Methods and Protocols U Garg 55–60 New York: Humana [Google Scholar]
  65. Klein CJ, Vrana JA, Theis JD, Dyck PJ, Dyck PJB. 65.  et al. 2011. Mass spectrometric–based proteomic analysis of amyloid neuropathy type in nerve tissue. Arch. Neurol. 68:195–99 [Google Scholar]
  66. Sethi S, Theis JD, Shiller SM, Nast CC, Harrison D. 66.  et al. 2012. Medullary amyloidosis associated with apolipoprotein A-IV deposition. Kidney Int 81:201–6 [Google Scholar]
  67. Nasr SH, Said SM, Valeri AM, Sethi S, Fidler ME. 67.  et al. 2013. The diagnosis and characteristics of renal heavy-chain and heavy/light-chain amyloidosis and their comparison with renal light-chain amyloidosis. Kidney Int 83:463–70 [Google Scholar]
  68. Said SM, Sethi S, Valeri AM, Chang A, Nast CC. 68.  et al. 2014. Characterization and outcomes of renal leukocyte chemotactic factor 2-associated amyloidosis. Kidney Int 86:370–77 [Google Scholar]
  69. Sethi S, Theis JD, Quint P, Maierhofer W, Kurtin PJ. 69.  et al. 2013. Renal amyloidosis associated with a novel sequence variant of gelsolin. Am. J. Kidney Dis. 61:161–66 [Google Scholar]
  70. Maleszewski JJ, Murray DL, Dispenzieri A, Grogan M, Pereira NL. 70.  et al. 2013. Relationship between monoclonal gammopathy and cardiac amyloid type. Cardiovasc. Pathol. 22:189–94 [Google Scholar]
  71. D'Souza A, Theis JD, Vrana JA, Buadi F, Dispenzieri A, Dogan A. 71.  2012. Localized insulin-derived amyloidosis: a potential pitfall in the diagnosis of systemic amyloidosis by fat aspirate. Am. J. Hematol. 87:E131–32 [Google Scholar]
  72. Chee CE, Lacy MQ, Dogan A, Zeldenrust SR, Gertz MA. 72.  2010. Pitfalls in the diagnosis of primary amyloidosis. Clin. Lymphoma Myeloma Leuk. 10:177–80 [Google Scholar]
  73. Romero-Camarero I, Jiang XY, Natkunam Y, Lu XQ, Vicente-Duenas C. 73.  et al. 2013. Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation. Nat. Commun. 4:1338 [Google Scholar]
  74. Valleix S, Gillmore JD, Bridoux F, Mangione PP, Dogan A. 74.  et al. 2012. Hereditary systemic amyloidosis due to Asp76Asn variant β2-microglobulin. N. Eng. J. Med. 366:2276–83 [Google Scholar]
  75. Valleix S, Verona G, Jourde-Chiche N, Nedelec B, Mangione PP. 75.  et al. 2016. D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile. Nat. Commun. 7:10353 [Google Scholar]
  76. D'Souza A, Theis JD, Vrana JA, Dogan A. 76.  2014. Pharmaceutical amyloidosis associated with subcutaneous insulin and enfuvirtide administration. Amyloid 21:71–75 [Google Scholar]
  77. Blumenfeld W, Hildebrandt RH. 77.  1993. Fine needle aspiration of abdominal fat for the diagnosis of amyloidosis. Acta Cytol 37:170–74 [Google Scholar]
  78. Westermark P. 78.  1995. Diagnosing amyloidosis. Scand. J. Rheumatol. 24:327–29 [Google Scholar]
  79. Fernández de Larrea C, Verga L, Morbini P, Klersy C, Lavatelli F. 79.  et al. 2015. A practical approach to the diagnosis of systemic amyloidoses. Blood 125:2239–44 [Google Scholar]
  80. Theis JD, Dasari S, Vrana JA, Mereuta OM, Grogg KL. 80.  et al. 2013. Proteome of amyloidosis: Mayo Clinic experience in 4139 cases. Blood 122:1900 [Google Scholar]
  81. Theis JD, Vrana JA, Gamez JD, Dogan A. 81.  2009. Mass spectrometry based proteomic analysis of AL amyloidosis: Immunoglobulin light chain gene constant region is an invariable part of amyloid deposits and provides valuable diagnostic target. Mod. Pathol. 22:377a [Google Scholar]
  82. Grogg KL, Aubry MC, Vrana JA, Theis JD, Dogan A. 82.  2013. Nodular pulmonary amyloidosis is characterized by localized immunoglobulin deposition and is frequently associated with an indolent B-cell lymphoproliferative disorder. Am. J. Surg. Pathol. 37:406–12 [Google Scholar]
  83. Dasari S, Theis JD, Vrana JA, Meureta OM, Quint PS. 83.  et al. 2015. Proteomic detection of immunoglobulin light chain variable region peptides from amyloidosis patient biopsies. J. Proteome Res. 14:1957–67 [Google Scholar]
  84. Comenzo RL, Zhang Y, Martinez C, Osman K, Herrera GA. 84.  2001. The tropism of organ involvement in primary systemic amyloidosis: contributions of Ig VL germ line gene use and clonal plasma cell burden. Blood 98:714–20 [Google Scholar]
  85. Abraham RS, Geyer SM, Price-Troska TL, Allmer C, Kyle RA. 85.  et al. 2003. Immunoglobulin light chain variable (V) region genes influence clinical presentation and outcome in light chain-associated amyloidosis (AL). Blood 101:3801–8 [Google Scholar]
  86. Yamagoe S, Kameoka Y, Hashimoto K, Mizuno S, Suzuki K. 86.  1998. Molecular cloning, structural characterization, and chromosomal mapping of the human LECT2 gene. Genomics 48:324–29 [Google Scholar]
  87. Yamagoe S, Mizuno S, Suzuki K. 87.  1998. Molecular cloning of human and bovine LECT2 having a neutrophil chemotactic activity and its specific expression in the liver. Biochim. Biophys. Acta 1396:105–13 [Google Scholar]
  88. Yamagoe S, Akasaka T, Uchida T, Hachiya T, Okabe T. 88.  et al. 1997. Expression of a neutrophil chemotactic protein LECT2 in human hepatocytes revealed by immunochemical studies using polyclonal and monoclonal antibodies to a recombinant LECT2. Biochem. Biophys. Res. Commun. 237:116–20 [Google Scholar]
  89. Yamagoe S, Yamakawa Y, Matsuo Y, Minowada J, Mizuno S, Suzuki K. 89.  1996. Purification and primary amino acid sequence of a novel neutrophil chemotactic factor LECT2. Immunol. Lett. 52:9–13 [Google Scholar]
  90. Hiraki Y, Inoue H, Kondo J, Kamizono A, Yoshitake Y. 90.  et al. 1996. A novel growth-promoting factor derived from fetal bovine cartilage, chondromodulin II. Purification and amino acid sequence. J. Biol. Chem. 271:22657–62 [Google Scholar]
  91. Ohtomi M, Nagai H, Ohtake H, Uchida T, Suzuki K. 91.  2007. Dynamic change in expression of LECT2 during liver regeneration after partial hepatectomy in mice. Biomed. Res 28247–53 [Google Scholar]
  92. Sato Y, Watanabe H, Kameyama H, Kobayashi T, Yamamoto S. 92.  et al. 2004. Serum LECT2 level as a prognostic indicator in acute liver failure. Transplant Proc 36:2359–61 [Google Scholar]
  93. Segawa Y, Itokazu Y, Inoue N, Saito T, Suzuki K. 93.  2001. Possible changes in expression of chemotaxin LECT2 mRNA in mouse liver after concanavalin A-induced hepatic injury. Biol. Pharm. Bull. 24:425–28 [Google Scholar]
  94. Ong HT, Tan PK, Wang SM, Hian Low DT, Ooi LL, Hui KM. 94.  2011. The tumor suppressor function of LECT2 in human hepatocellular carcinoma makes it a potential therapeutic target. Cancer Gene. Ther. 18:399–406 [Google Scholar]
  95. Uchida T, Nagai H, Gotoh K, Kanagawa H, Kouyama H. 95.  et al. 1999. Expression pattern of a newly recognized protein, LECT2, in hepatocellular carcinoma and its premalignant lesion. Pathol. Int. 49:147–51 [Google Scholar]
  96. Benson MD, James S, Scott K, Liepnieks JJ, Kluve-Beckerman B. 96.  2008. Leukocyte chemotactic factor 2: a novel renal amyloid protein. Kidney Int 74:218–22 [Google Scholar]
  97. Murphy CL, Wang S, Kestler D, Larsen C, Benson D. 97.  et al. 2010. Leukocyte chemotactic factor 2 (LECT2)-associated renal amyloidosis: a case series. Am. J. Kidney Dis. 56:1100–7 [Google Scholar]
  98. Dogan A, Theis JD, Vrana JA, Jimenez-Zepeda VH, Lacy MQ. 98.  et al. 2010. Clinical and pathological phenotype of leukocyte cell-derived chemotaxin-2 (LECT2) amyloidosis (ALECT2). Amyloid 17:69–70 [Google Scholar]
  99. Mereuta OM, Theis JD, Vrana JA, Law ME, Grogg KL. 99.  et al. 2014. Leukocyte cell-derived chemotaxin 2 (LECT2)-associated amyloidosis is a frequent cause of hepatic amyloidosis in the United States. Blood 123:1479–82 [Google Scholar]
  100. Comenzo RL. 100.  2014. LECT2 makes the amyloid list. Blood 123:1436–37 [Google Scholar]
  101. Chandan VS, Shah SS, Lam-Himlin DM, Petris GD, Mereuta OM. 101.  et al. 2015. Globular hepatic amyloid is highly sensitive and specific for LECT2 amyloidosis. Am. J. Surg. Pathol. 39:558–64 [Google Scholar]
  102. Nasr SH, Dogan A, Larsen CP. 102.  2015. Leukocyte cell-derived chemotaxin 2-associated amyloidosis: a recently recognized disease with distinct clinicopathologic characteristics. Clin. J. Am. Soc. Nephrol. 10:2084–93 [Google Scholar]
  103. Larsen CP, Beggs ML, Wilson JD, Lathrop SL. 103.  2016. Prevalence and organ distribution of leukocyte chemotactic factor 2 amyloidosis (ALECT2) among decedents in New Mexico. Amyloid 23:119–23 [Google Scholar]
  104. Larsen CP, Ismail W, Kurtin PJ, Vrana JA, Dasari S, Nasr SH. 104.  2016. Leukocyte chemotactic factor 2 amyloidosis (ALECT2) is a common form of renal amyloidosis among Egyptians. Mod. Pathol. 29:416–20 [Google Scholar]
  105. Hutton HL, DeMarco ML, Magil AB, Taylor P. 105.  2014. Renal leukocyte chemotactic factor 2 (LECT2) amyloidosis in First Nations people in Northern British Columbia, Canada: a report of 4 cases. Am. J. Kidney Dis. 64:790–92 [Google Scholar]
  106. Larsen BT, Mereuta OM, Dasari S, Fayyaz AU, Theis JD. 106.  et al. 2016. Correlation of histomorphological pattern of cardiac amyloid deposition with amyloid type: a histological and proteomic analysis of 108 cases. Histopathology 68:648–56 [Google Scholar]
  107. Larsen CP, Kossmann RJ, Beggs ML, Solomon A, Walker PD. 107.  2014. Clinical, morphologic, and genetic features of renal leukocyte chemotactic factor 2 amyloidosis. Kidney Int 86:378–82 [Google Scholar]
  108. Sipe JD, Benson MD, Buxbaum JN, Ikeda S, Merlini G. 108.  2012. Amyloid fibril protein nomenclature: 2012 recommendations from the Nomenclature Committee of the International Society of Amyloidosis. Amyloid 19:167–70 [Google Scholar]
  109. Benson MD. 109.  2010. LECT2 amyloidosis. Kidney Int 77:757–59 [Google Scholar]
  110. Murphy C, Wang S, Kestler D, Larsen C, Benson D. 110.  et al. 2011. Leukocyte chemotactic factor 2 (LECT2)-associated renal amyloidosis. Amyloid 18:Suppl. 1223–25 [Google Scholar]
  111. Kameoka Y, Yamagoe S, Hatano Y, Kasama T, Suzuki K. 111.  2000. Val58Ile polymorphism of the neutrophil chemoattractant LECT2 and rheumatoid arthritis in the Japanese population. Arthritis Rheum 43:1419–20 [Google Scholar]
  112. Hamidi Asl L, Liepnieks JJ, Uemichi T, Rebibou JM, Justrabo E. 112.  et al. 1997. Renal amyloidosis with a frame shift mutation in fibrinogen Aα-chain gene producing a novel amyloid protein. Blood 90:4799–805 [Google Scholar]
  113. Buck FS, Koss MN. 113.  1991. Hepatic amyloidosis: morphologic differences between systemic AL and AA types. Hum. Pathol. 22:904–7 [Google Scholar]
  114. Damlaj M, Amre R, Wong P, How J. 114.  2014. Hepatic ALECT-2 amyloidosis causing portal hypertension and recurrent variceal bleeding: a case report and review of the literature. Am. J. Clin. Pathol. 141:288–91 [Google Scholar]
  115. Jimenez JL, Nettleton EJ, Bouchard M, Robinson CV, Dobson CM, Saibil HR. 115.  2002. The protofilament structure of insulin amyloid fibrils. PNAS 99:9196–201 [Google Scholar]
  116. Dogan A, Vrana JA, Theis JD, Gamez JD, Kurtin PJ, Grogg KL. 116.  2010. Mass spectrometry-based proteomic analysis of iatrogenic insulin-mediated amyloidosis (AIns). Amyloid 17:114 [Google Scholar]
  117. Nagase T, Katsura Y, Iwaki Y, Nemoto K, Sekine H. 117.  et al. 2009. The insulin ball. Lancet 373:184 [Google Scholar]
  118. Yumlu S, Barany R, Eriksson M, Rocken C. 118.  2009. Localized insulin-derived amyloidosis in patients with diabetes mellitus: a case report. Hum. Pathol. 40:1655–60 [Google Scholar]
  119. Swift B, Hawkins PN, Richards C, Gregory R. 119.  2002. Examination of insulin injection sites: an unexpected finding of localized amyloidosis. Diabet. Med. 19:881–82 [Google Scholar]
  120. Mirza RA, Turiansky GW. 120.  2012. Enfuvirtide and cutaneous injection-site reactions. J. Drugs Dermatol. 11:e35–38 [Google Scholar]
  121. Naujokas A, Vidal CI, Mercer SE, Harp J, Kurtin PJ. 121.  et al. 2012. A novel form of amyloid deposited at the site of enfuvirtide injection. J. Cutan. Pathol. 39:220–21 [Google Scholar]
  122. Morilla ME, Kocher J, Harmaty M. 122.  2009. Localized amyloidosis at the site of enfuvirtide injection. Ann. Intern. Med. 151:515–16 [Google Scholar]
  123. Maggi P, Ladisa N, Cinori E, Altobella A, Pastore G, Filotico R. 123.  2004. Cutaneous injection site reactions to long-term therapy with enfuvirtide. J. Antimicrob. Chemother. 53:678–81 [Google Scholar]
  124. Endo JO, Rocken C, Lamb S, Harris RM, Bowen AR. 124.  2010. Nodular amyloidosis in a diabetic patient with frequent hypoglycemia: sequelae of repeatedly injecting insulin without site rotation. J. Am. Acad. Dermatol. 63:e113–14 [Google Scholar]
  125. Zingraff JJ, Noel LH, Bardin T, Atienza C, Zins B. 125.  et al. 1990. β2-microglobulin amyloidosis in chronic renal failure. N. Engl. J. Med. 323:1070–71 [Google Scholar]
  126. Stoppini M, Bellotti V. 126.  2015. Systemic amyloidosis: lessons from β2-microglobulin. J. Biol. Chem. 290:9951–58 [Google Scholar]
  127. Nichols WC, Dwulet FE, Liepnieks J, Benson MD. 127.  1988. Variant apolipoprotein AI as a major constituent of a human hereditary amyloid. Biochem. Biophys. Res. Commun. 156:762–68 [Google Scholar]
  128. Benson MD. 128.  1998. Apolipoprotein AI and amyloidosis: a genetic model for aging. Kidney Int 53:508–9 [Google Scholar]
  129. Rowczenio D, Wechalekar A. 129. , eds. 2015. Apolipoprotein A-I (APOA1), accessed on 10/14/2016. http://www.amyloidosismutations.com
  130. Rowczenio D, Dogan A, Theis JD, Vrana JA, Lachmann HJ. 130.  et al. 2011. Amyloidogenicity and clinical phenotype associated with five novel mutations in apolipoprotein A-I. Am. J. Pathol. 179:1978–87 [Google Scholar]
  131. Eriksson M, Schonland S, Yumlu S, Hegenbart U, von Hutten H. 131.  et al. 2009. Hereditary apolipoprotein AI-associated amyloidosis in surgical pathology specimens: identification of three novel mutations in the APOA1 gene. J. Mol. Diagn. 11:257–62 [Google Scholar]

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