Erratum to: α1-Antitrypsin deficiency (Nature Reviews Disease Primers, (2016), 2, (16051), 10.1038/nrdp.2016.51);α1-Antitrypsin deficiency

Nature Reviews Disease Primers

Volumn 2, Issue , 2016, Pages

  Greene, Catherine M ^a   Marciniak, Stefan J ^b   Teckman, Jeffrey ^c   Ferrarotti, Ilaria ^d   Brantly, Mark L ^e   Lomas, David A ^f   Stoller, James K ^g   McElvaney, Noel G ^a  

^a BEAUMONT HOSPITAL   (Ireland)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF PAVIA   (Italy)

^e UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^f UNIVERSITY COLLEGE LONDON   (United Kingdom)

^g LERNER RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADRENERGIC RECEPTOR STIMULATING AGENT; ALPHA 1 ANTITRYPSIN; LEUKOCYTE ELASTASE; MUSCARINIC RECEPTOR BLOCKING AGENT; SERPINA1 PROTEIN, HUMAN;

ALLELE; ALPHA 1 ANTITRYPSIN DEFICIENCY; ARTICLE; ASTHMA; CHRONIC OBSTRUCTIVE LUNG DISEASE; DIAGNOSTIC TEST; DISEASE ASSOCIATION; ENDOPLASMIC RETICULUM STRESS; ENZYME ACTIVITY; GENE MUTATION; GENE SILENCING; HUMAN; LIFE EXPECTANCY; LIVER CELL; LIVER CIRRHOSIS; LIVER DISEASE; LIVER FAILURE; LIVER TRANSPLANTATION; LUNG COMPLICATION; PATHOPHYSIOLOGY; PATIENT SELECTION; PRIORITY JOURNAL; PROTEINASE INHIBITION; QUALITY OF LIFE; RISK FACTOR; COMPLICATION; DELAYED DIAGNOSIS; DYSPNEA; EMPHYSEMA; EPITHELIUM CELL; GENETICS; IMMUNOLOGY; METABOLISM; MONOCYTE; MORTALITY; MUTATION; NEUTROPHIL; PHYSIOLOGY; SMOKING;

ALPHA 1-ANTITRYPSIN; ALPHA 1-ANTITRYPSIN DEFICIENCY; DELAYED DIAGNOSIS; DYSPNEA; EMPHYSEMA; EPITHELIAL CELLS; HUMANS; LIVER DISEASES; MONOCYTES; MUTATION; NEUTROPHILS; SMOKING;

EID: 84991527671     PISSN: None     EISSN: 2056676X     Source Type: Journal    
DOI: 10.1038/s41572-018-0043-2     Document Type: Erratum

References (192)

1. Laurell, C. B.& Eriksson, S. The electrophoretic α1 globulin pattern of serum in α1 antitrypsin deficiency. 1963. COPD 10 (Suppl. 1), 3-8 (2013).
2. Stoller, J. K., & Brantly, M. The challenge of detecting alpha 1 antitrypsin deficiency. COPD 10 (Suppl. 1), 26-34 (2013).
3. Stoller, J. K., Smith, P., Yang, P., & Spray, J. Physical and social impact of alpha1 antitrypsin deficiency: results of a survey. Cleve. Clin. J. Med. 61, 461-467 (1994).
4. de Serres, F. J., Blanco, I., & Fernandez Bustillo, E. PI S and PI Z alpha 1 antitrypsin deficiency worldwide. A review of existing genetic epidemiological data. Monaldi Arch. Chest Dis. 67, 184-208 (2007).
5. Sveger, T. Liver disease in alpha1 antitrypsin deficiency detected by screening of 200, 000 infants. N. Engl. J. Med. 294, 1316-1321 (1976).
6. Silverman, E. K., et al. Alpha 1 antitrypsin deficiency. High prevalence in the St. Louis area determined by direct population screening. Am. Rev. Respir. Dis. 140, 961-966 (1989).
7. Thun, G. A., et al. Causal and synthetic associations of variants in the SERPINA gene cluster with alpha1 antitrypsin serum levels. PLoS Genet. 9, e1003585 (2013).
8. O?Brien, M. E., et al. The impact of smoke exposure on the clinical phenotype of alpha 1 antitrypsin deficiency in Ireland: exploiting a national registry to understand a rare disease. COPD 12 (Suppl. 1), 2-9 (2015).
9. Tanash, H. A., Nystedt D?zakin, M., Montero, L. C., Sveger, T., & Piitulainen, E. The Swedish α1 antitrypsin screening study: health status and lung and liver function at age 34. Ann. Am. Thorac Soc. 12, 807-812 (2015).
10. Piitulainen, E., & Tanash, H. A. The clinical profile of subjects Included in the Swedish national register on individuals with severe alpha 1 antitrypsin deficiency. COPD 12 (Suppl. 1), 36-41 (2015).
11. McAloon, C. J., Wood, A. M., Gough, S. C., & Stockley, R. A. Matrix metalloprotease polymorphisms are associated with gas transfer in alpha 1 antitrypsin deficiency. Ther. Adv. Respir. Dis. 3, 23-30 (2009).
12. Wood, A. M., et al. The TNFalpha gene relates to clinical phenotype in alpha 1 antitrypsin deficiency. Respir. Res. 9, 52 (2008).
13. Demeo, D. L., et al. IL10 polymorphisms are associated with airflow obstruction in severe α1-antitrypsin deficiency. Am. J. Respir. Cell. Mol. Biol. 38, 114-120 (2008).
14. Kim, W. J., et al. Association of IREB2 and CHRNA3 polymorphisms with airflow obstruction in severe alpha 1 antitrypsin deficiency. Respir. Res. 13, 16 (2012).
15. Alam, S., et al. Z α1 antitrypsin confers a proinflammatory phenotype that contributes to chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 189, 909-931 (2014).
16. Wood, A. M., Harrison, R. M., Semple, S., Ayres, J. G., & Stockley, R. A. Outdoor air pollution is associated with disease severity in α1-antitrypsin deficiency. Eur. Respir. J. 34, 346-353 (2009).
17. Wood, A. M., Harrison, R. M., Semple, S., Ayres, J. G., & Stockley, R. A. Outdoor air pollution is associated with rapid decline of lung function in α 1 antitrypsin deficiency. Occup. Environ. Med. 67, 556-561 (2010).
18. Mehta, A. J., et al. Interactions between SERPINA1 PiMZ genotype, occupational exposure and lung function decline. Occup. Environ. Med. 71, 234-240 (2014).
19. Molloy, K., et al. Clarification of the risk of chronic obstructive pulmonary disease in α1 antitrypsin deficiency PiMZ heterozygotes. Am. J. Respir. Crit. Care Med. 189, 419-427 (2014).
20. Parmar, J. S., et al. Polymers of α1-antitrypsin are chemotactic for human neutrophils: a new paradigm for the pathogenesis of emphysema. Am. J. Respir. Cell. Mol. Biol. 26, 723-730 (2002).
21. Kalsheker, N., Morley, S., & Morgan, K. Gene regulation of the serine proteinase inhibitors α1-antitrypsin and α1-antichymotrypsin. Biochem. Soc. Trans. 30, 93-98 (2002).
22. Hafeez, W., Ciliberto, G., & Perlmutter, D. H. Constitutive and modulated expression of the human alpha 1 antitrypsin gene. Different transcriptional initiation sites used in three different cell types. J. Clin. Invest. 89, 1214-1222 (1992).
23. Knoell, D. L., Ralston, D. R., Coulter, K. R., & Wewers, M. D. Alpha 1 antitrypsin and protease complexation is induced by lipopolysaccharide, interleukin 1beta, and tumor necrosis factor-alpha in monocytes. Am. J. Respir. Crit. Care Med. 157, 246-255 (1998).
24. Cichy, J., Potempa, J., & Travis, J. Biosynthesis of α1 -proteinase inhibitor by human lung-derived epithelial cells. J. Biol. Chem. 272, 8250-8255 (1997).
25. Sallenave, J. M., Tremblay, G. M., Gauldie, J., & Richards, C. D. Oncostatin M, but not interleukin 6 or leukemia inhibitory factor, stimulates expression of alpha1 proteinase inhibitor in A549 human alveolar epithelial cells. J. Interferon Cytokine Res. 17, 337-346 (1997).
26. Cichy, J., Rose John, S., & Travis, J. Oncostatin M, leukaemia-inhibitory factor and interleukin 6 trigger different effects on α1 proteinase inhibitor synthesis in human lung-derived epithelial cells. Biochem. J. 329, 335-339 (1998).
27. Kulig, P., & Cichy, J. Acute phase mediator oncostatin M regulates affinity of α1-protease inhibitor for concanavalin A in hepatoma-derived but not lung-derived epithelial cells. Cytokine 30, 269-274 (2005).
28. Bosco, D., et al. Expression and secretion of alpha1 proteinase inhibitor are regulated by proinflammatory cytokines in human pancreatic islet cells. Diabetologia 48, 1523-1533 (2005).
29. Matamala, N., et al. Alternative transcripts of the SERPINA1 gene in alpha 1 antitrypsin deficiency. J. Transl Med. 13, 211 (2015).
30. Gooptu, B., Dickens, J. A., & Lomas, D. A. The molecular and cellular pathology of α1-antitrypsin deficiency. Trends Mol. Med. 20, 116-127 (2014).
31. Silva, D., et al. Alpha 1 antitrypsin (SERPINA1) mutation spectrum: three novel variants and haplotype characterization of rare deficiency alleles identified in Portugal. Respir. Med. 116, 8-18 (2016).
32. Ferrarotti, I., et al. Identification and characterisation of eight novel SERPINA1 null mutations. Orphanet J. Rare Dis. 9, 172 (2014).
33. Huntington, J. A., Read, R. J., & Carrell, R. W. Structure of a serpin-protease complex shows inhibition by deformation. Nature 407, 923-926 (2000).
34. Lomas, D. A., Evans, D. L., Finch, J. T., & Carrell, R. W. The mechanism of Z α1 antitrypsin accumulation in the liver. Nature 357, 605-607 (1992).
35. Miranda, E., et al. A novel monoclonal antibody to characterise pathogenic polymers in liver disease associated with α1 antitrypsin deficiency. Hepatology 52, 1078-1088 (2010).
36. Lomas, D. A., Finch, J. T., Seyama, K., Nukiwa, T., & Carrell, R. W. α1 Antitrypsin Siiyama (Ser53?Phe); further evidence for intracellular loop-sheet polymerisation. J. Biol. Chem. 268, 15333-15335 (1993).
37. Lomas, D. A., et al. α1-Antitrypsin Mmalton (Phe52 -deleted) forms loop-sheet polymers in vivo: evidence for the C sheet mechanism of polymerisation. J. Biol. Chem. 270, 16864-16870 (1995).
38. Ordonez, A., & Marciniak, S. J. in The Serpin Family: Proteins with Multiple Functions in Health and Disease (ed. Geiger, M.) 229-251 (2015).
39. Irving, J. A., Haq, I., Dickens, J. A., Faull, S. V., & Lomas, D. A. Altered native stability is the dominant basis for susceptibility of α1-antitrypsin mutants to polymerization. Biochem. J. 460, 103-115 (2014).
40. Yamasaki, M., Li, W., Johnson, D. J., & Huntington, J. A. Crystal structure of a stable dimer reveals the molecular basis of serpin polymerization. Nature 455, 1255-1258 (2008).
41. Yamasaki, M., Sendall, T. J., Pearce, M. C., Whisstock, J. C., & Huntington, J. A. Molecular basis of α1 antitrypsin deficiency revealed by the structure of a domain-swapped trimer. EMBO Rep. 12, 1011-1017 (2011).
42. Krishnan, B., & Gierasch, L. M. Dynamic local unfolding in the serpin α-1 antitrypsin provides a mechanism for loop insertion and polymerization. Nat. Struct. Mol. Biol. 18, 222-226 (2011).
43. Behrens, M. A., et al. The shapes of Z-α1 antitrypsin polymers in solution support the C terminal domain-swap mechanism of polymerization. Biophys. J. 107, 1905-1912 (2014).
44. Weldon, S., et al. Decreased levels of secretory leucoprotease inhibitor in the Pseudomonas-infected cystic fibrosis lung are due to neutrophil elastase degradation. J. Immunol. 183, 8148-8156 (2009).
45. Nemoto, E., et al. Cleavage of CD14 on human gingival fibroblasts cocultured with activated neutrophils is mediated by human leukocyte elastase resulting in down-regulation of lipopolysaccharide-induced IL 8 production. J. Immunol. 165, 5807-5813 (2000).
46. Hartl, D., et al. Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease. Nat. Med. 13, 1423-1430 (2007).
47. Bergin, D. A., et al. α 1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL 8. J. Clin. Invest. 120, 4236-4250 (2010).
48. Bergin, D. A., et al. The circulating proteinase inhibitor α 1 antitrypsin regulates neutrophil degranulation and autoimmunity. Sci. Transl Med. 6, 217ra1 (2014).
49. Yasutake, A., & Powers, J. C. Reactivity of human leukocyte elastase and porcine pancreatic elastase toward peptide 4 nitroanilides containing model desmosine residues. Evidence that human leukocyte elastase is selective for cross-linked regions of elastin. Biochemistry 20, 3675-3679 (1981).
50. Kafienah, W., Buttle, D. J., Burnett, D., & Hollander, A. P. Cleavage of native type I collagen by human neutrophil elastase. Biochem. J. 330, 897-902 (1998).
51. McDonald, J. A., & Kelley, D. G. Degradation of fibronectin by human leukocyte elastase. Release of biologically active fragments. J. Biol. Chem. 255, 8848-8858 (1980).
52. Malemud, C. J., & Janoff, A. Identification of neutral proteases in human neutrophil granules that degrade articular cartilage proteoglycan. Arthritis Rheum. 18, 361-368 (1975
53. Geraghty, P., et al. Neutrophil elastase up regulates cathepsin B and matrix metalloprotease 2 expression. J. Immunol. 178, 5871-5878 (2007).
54. Shao, M. X., & Nadel, J. A. Dual oxidase 1 dependent MUC5AC mucin expression in cultured human airway epithelial cells. Proc. Natl Acad. Sci. USA 102, 767-772 (2005).
55. Shao, M. X., & Nadel, J. A. Neutrophil elastase induces MUC5AC mucin production in human airway epithelial cells via a cascade involving protein kinase C, reactive oxygen species, and TNF-α-converting enzyme. J. Immunol. 175, 4009-4016 (2005).
56. Bergin, D. A., et al. Activation of the epidermal growth factor receptor (EGFR) by a novel metalloprotease pathway. J. Biol. Chem. 283, 31736-31744 (2008).
57. Okada, Y., et al. Inactivation of tissue inhibitor of metalloproteinases by neutrophil elastase and other serine proteinases. FEBS Lett. 229, 157-160 (1988).
58. Guyot, N., et al. Elafin, an elastase-specific inhibitor, is cleaved by its cognate enzyme neutrophil elastase in sputum from individuals with cystic fibrosis. J. Biol. Chem. 283, 32377-32385 (2008).
59. Abrahamson, M., et al. Human cystatin C. Role of the N terminal segment in the inhibition of human cysteine proteinases and in its inactivation by leucocyte elastase. Biochem. J. 273, 621-626 (1991).
60. Greene, C. M., Hassan, T., Molloy, K., & McElvaney, N. G. The role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and α 1 anti-trypsin deficiency. Expert Rev. Respir. Med. 5, 395-411 (2011).
61. Petrache, I., et al. α 1 Antitrypsin inhibits caspase 3 activity, preventing lung endothelial cell apoptosis. Am. J. Pathol. 169, 1155-1166 (2006).
62. O?Dwyer, C. A., et al. The BLT1 inhibitory function of α 1 antitrypsin augmentation therapy disrupts leukotriene B4 neutrophil signaling. J. Immunol. 195, 3628-3641 (2015).
63. Hurley, K., et al. Alpha 1 antitrypsin augmentation therapy corrects accelerated neutrophil apoptosis in deficient individuals. J. Immunol. 193, 3978-3991 (2014).
64. Geraghty, P., et al. α1-Antitrypsin activates protein phosphatase 2A to counter lung inflammatory responses. Am. J. Respir. Crit. Care Med. 190, 1229-1242 (2014).
65. Lindblad, D., Blomenkamp, K., & Teckman, J. Alpha 1 antitrypsin mutant Z protein content in individual hepatocytes correlates with cell death in a mouse model. Hepatology 46, 1228-1235 (2007).
66. Kroeger, H., et al. Endoplasmic reticulum-associated degradation (ERAD) and autophagy cooperate to degrade polymerogenic mutant serpins. J. Biol. Chem. 284, 22793-22802 (2009).
67. Teckman, J. H., et al. The proteasome participates in degradation of mutant α1 antitrypsin Z in the endoplasmic reticulum of hepatoma-derived hepatocytes. J. Biol. Chem. 276, 44865-44872 (2001).
68. Kruse, K. B., Brodsky, J. L., & McCracken, A. A. Characterization of an ERAD gene as VPS30/ATG6 reveals two alternative and functionally distinct protein quality control pathways: one for soluble Z variant of human α 1 proteinase inhibitor (A1PiZ) and another for aggregates of A1PiZ. Mol. Biol. Cell 17, 203-212 (2006).
69. Ekeowa, U. I., et al. Defining the mechanism of polymerization in the serpinopathies. Proc. Natl Acad. Sci. USA 107, 17146-17151 (2010).
70. Hosokawa, N., et al. Enhancement of endoplasmic reticulum (ER) degradation of misfolded Null Hong Kong α1-antitrypsin by human ER mannosidaseI. J. Biol. Chem. 278, 26287-26294 (2003).
71. Cabral, C. M., Choudhury, P., Liu, Y., & Sifers, R. N. Processing by endoplasmic reticulum mannosidases partitions a secretion-impaired glycoprotein into distinct disposal pathways. J. Biol. Chem. 275, 25015-25022 (2000).
72. Wu, Y., Swulius, M. T., Moremen, K. W., & Sifers, R. N. Elucidation of the molecular logic by which misfolded α1 antitrypsin is preferentially selected for degradation. Proc. Natl Acad. Sci. USA 100, 8229-8234 (2003).
73. Cabral, C. M., Liu, Y., Moremen, K. W., & Sifers, R. N. Organizational diversity among distinct glycoprotein endoplasmic reticulum-associated degradation programs. Mol. Biol. Cell 13, 2639-2650 (2002).
74. Hidvegi, T., et al. An autophagy-enhancing drug promotes degradation of mutant α1-antitrypsin Z and reduces hepatic fibrosis. Science 329, 229-232 (2010).
75. Marciniak, S. J., & Lomas, D. A. Alpha1-antitrypsin deficiency and autophagy. N. Engl. J. Med. 363, 1863-1864 (2010).
76. Chambers, J. E., & Marciniak, S. J. Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. 2. Protein misfolding and ER stress. Am. J. Physiol. Cell Physiol. 307, C657-C670 (2014).
77. Ron, D., & Walter, P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 8, 519-529 (2007).
78. Sifers, R. N., Brashears Macatee, S., Kidd, V. J., Muensch, H., & Woo, S. L. A frameshift mutation results in a truncated α1 antitrypsin that is retained within the rough endoplasmic reticulum. J. Biol. Chem. 263, 7330-7335 (1988).
79. Brodbeck, R. M., & Brown, J. L. Secretion of α-1 proteinase inhibitor requires an almost full length molecule. J. Biol. Chem. 267, 294-297 (1992).
80. Faber, J. P., et al. Identification and DNA sequence analysis of 15 new alpha 1 antitrypsin variants, including two PIQ0 alleles and one deficient PI M allele. Am. J. Hum. Genet. 55, 1113-1121 (1994).
81. Liu, Y., Choudhury, P., Cabral, C. M., & Sifers, R. N. Intracellular disposal of incompletely folded human α1-antitrypsin involves release from calnexin and post translational trimming of asparagine-linked oligosaccharides. J. Biol. Chem. 272, 7946-7951 (1997).
82. Hidvegi, T., Schmidt, B. Z., Hale, P., & Perlmutter, D. H. Accumulation of mutant α1-antitrypsin Z in the endoplasmic reticulum activates caspases 4 and -12, NF?B, and BAP31 but not the unfolded protein response. J. Biol. Chem. 280, 39002-39015 (2005).
83. Ordonez, A., et al. Endoplasmic reticulum polymers impair luminal protein mobility and sensitize to cellular stress in alpha1-antitrypsin deficiency. Hepatology 57, 2049-2060 (2013).
84. Bertolotti, A., Zhang, Y., Hendershot, L. M., Harding, H. P., & Ron, D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat. Cell Biol. 2, 326-332 (2000).
85. Credle, J. J., Finer Moore, J. S., Papa, F. R., Stroud, R. M., & Walter, P. On the mechanism of sensing unfolded protein in the endoplasmic reticulum. Proc. Natl Acad. Sci. USA 102, 18773-18784 (2005).
86. Graham, K. S., Le, A., & Sifers, R. N. Accumulation of the insoluble PiZ variant of human α1 antitrypsin within the hepatic endoplasmic reticulum does not elevate the steady-state level of grp78/BiP. J. Biol. Chem. 265, 20463-20468 (1990).
87. Lawless, M. W., et al. Activation of endoplasmic reticulum-specific stress responses associated with the conformational disease Z α1 antitrypsin deficiency. J. Immunol. 172, 5722-5726 (2004).
88. Davies, M. J., et al. Neuroserpin polymers activate NF ?B by a calcium signaling pathway that is independent of the unfolded protein response. J. Biol. Chem. 284, 18202-18209 (2009).
89. van ?t Wout, E. F., et al. Increased ERK signalling promotes inflammatory signalling in primary airway epithelial cells expressing Z α1-antitrypsin. Hum. Mol. Genet. 23, 929-941 (2014).
90. Van?t Wout, E. F., et al. Function of monocytes and monocyte-derived macrophages in α1-antitrypsin deficiency. Eur. Respir. J. 45, 365-376 (2015).
91. Carroll, T. P., et al. Evidence for unfolded protein response activation in monocytes from individuals with α 1 antitrypsin deficiency. J. Immunol. 184, 4538-4546 (2010).
92. Tan, L., et al. Circulating polymers in α1-antitrypsin deficiency. Eur. Respir. J. 43, 1501-1504 (2014).
93. Elliott, P. R., Bilton, D., & Lomas, D. A. Lung polymers in Z α1 -antitrypsin deficiency-related emphysema. Am. J. Respir. Cell Mol. Biol. 18, 670-674 (1998).
94. Mahadeva, R., et al. Polymers of Z α1-antitrypsin co localize with neutrophils in emphysematous alveoli and are chemotactic in vivo. Am. J. Pathol. 166, 377-386 (2005).
95. Fra, A., et al. Polymers of Z α1-antitrypsin are secreted in cell models of disease. Eur. Respir. J. 47, 1005-1009 (2016).
96. Blanco, I., Lipsker, D., Lara, B., & Janciauskiene, S. Neutrophilic panniculitis associated with alpha 1 antitrypsin deficiency: an update. Br. J. Dermatol. 174, 753-762 (2016).
97. Greulich, T., et al. Alpha1-antitrypsin deficiency - diagnostic testing and disease awareness in Germany and Italy. Respir. Med. 107, 1400-1408 (2013).
98. Jain, A., McCarthy, K., Xu, M., & Stoller, J. K. Impact of a clinical decision support system in an electronic health record to enhance detection of α1-antitrypsin deficiency. Chest 140, 198-204 (2011).
99. American Thoracic Society & European Respiratory Society. American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha 1 antitrypsin deficiency. Am. J. Respir. Crit. Care Med. 168, 818-900 (2003).
100. Brantly, M. in Alpha 1 Antitrypsin Deficiency: Biology, Pathogenesis, Clinical Manifestations, Therapy (ed. Crystal, R. G.) 211-226 (Marcel Dekker, 1996).
101. McElvaney, N. G. Diagnosing α1-antitrypsin deficiency: how to improve the current algorithm. Eur. Respir. Rev. 24, 52-57 (2015).
102. Brantly, M. Efficient and accurate approaches to the laboratory diagnosis of α1 antitrypsin deficiency: the promise of early diagnosis and intervention. Clin. Chem. 52, 2180-2181 (2006).
103. Carroll, T. P., et al. The prevalence of alpha 1 antitrypsin deficiency in Ireland. Respir. Res. 12, 91 (2011).
104. Sveger, T., & Thelin, T. Four-year-old children with alpha 1 antitrypsin deficiency. Clinical follow up and parental attitudes towards neonatal screening. Acta Paediatr. Scand. 70, 171-177 (1981).
105. Global Initiative for Chronic Obstructive Lung Disease. Global Initiative for Chronic Obstructive Lung Disease (Global Initiative for Chronic Obstructive Lung Disease, Inc., 2014).
106. [No authors listed.] Alpha 1 antitrypsin deficiency: memorandum from a WHO meeting. Bull. World Health Organ. 75, 397-415 (1997).
107. EURORDIS-NORD-CORD. EURORDIS-NORD-CORD joint declaration of 10 key principles for rare disease patient registries. EURODIS http: // download.eurordis.org/documents/pdf/EURORDIS- NORD-CORD-JointDec-Registries-FINAL.pdf (2012).
108. [No authors listed.] Survival and FEV1 decline in individuals with severe deficiency of α1-antitrypsin. The Alpha 1 Antitrypsin Deficiency Registry Study Group. Am. J. Respir. Crit. Care Med. 158, 49-59 (1998).
109. Strange, C., et al. The United States Alpha 1 Foundation Research Registry: genesis, impact and future. COPD 12 (Suppl. 1), 42-45 (2015).
110. Stockley, R. A., et al. Ongoing research in Europe: Alpha One International Registry (AIR) objectives and development. Eur. Respir. J. 29, 582-586 (2007).
111. Chorostowska Wynimko, J., Struniawski, R., Sliwinski, P., Wajda, B., & Czajkowska Malinowska, M. The national alpha 1 antitrypsin deficiency registry in Poland. COPD 12 (Suppl. 1), 22-26 (2015).
112. Stoller, J. K., et al. [American Thoracic Society/ European Respiratory Society Statement: standards for the diagnosis and management of individuals with alpha 1 antitrypsin deficiency]. Pneumologie 59, 36-68 (in German) (2005).
113. Mayer, A. S., et al. Occupational exposure risks in individuals with PI Z α1-antitrypsin deficiency. Am. J. Respir. Crit. Care Med. 162, 553-558 (2000).
114. Mayer, A. S., et al. Risk factors for symptom onset in PI Z alpha 1 antitrypsin deficiency. Int. J. Chron. Obstruct Pulmon Dis. 1, 485-492 (2006).
115. Larsson, C. Natural history and life expectancy in severe alpha1 antitrypsin deficiency, Pi Z. Acta Med. Scand. 204, 345-351 (1978).
116. Strange, C., et al. Genetic testing for alpha1 antitrypsin deficiency. Genet. Med. 6, 204-210 (2004).
117. Strange, C., et al. Genetic testing of minors for alpha1 antitrypsin deficiency. Arch. Pediatr. Adolesc. Med. 160, 531-534 (2006).
118. Piitulainen, E., Tornling, G., & Eriksson, S. Effect of age and occupational exposure to airway irritants on lung function in non-smoking individuals with α1 antitrypsin deficiency (PiZZ). Thorax 52, 244-248 (1997).
119. Eriksson, S., Carlson, J., & Velez, R. Risk of cirrhosis and primary liver cancer in alpha1-antitrypsin deficiency. N. Engl. J. Med. 314, 736-739 (1986
120. Nelson, D. R., Teckman, J., Di Bisceglie, A. M., & Brenner, D. A. Diagnosis and management of patients with α1-antitrypsin (A1AT) deficiency. Clin. Gastroenterol. Hepatol. 10, 575-580 (2012).
121. He, X. X., Li, Y., Ren, H. P., Tian, D. A., & Lin, J. S. [2010 guideline for the management of hepatocellular carcinoma recommended by the American Association for the Study of Liver Diseases]. Zhonghua Gan Zang Bing Za Zhi 19, 249-250 (in Chinese) (2011).
122. Pillai, A. P., Turner, A. M., & Stockley, R. A. Relationship of the 2011 Global Initiative for Chronic Obstructive Lung Disease strategy to clinically relevant outcomes in individuals with α1-antitrypsin deficiency. Ann. Am. Thorac Soc. 11, 859-864 (2014).
123. Wewers, M. D., et al. Replacement therapy for alpha1 antitrypsin deficiency associated with emphysema. N. Engl. J. Med. 316, 1055-1062 (1987).
124. Chapman, K. R., et al. Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet 386, 360-368 (2015).
125. Chotirmall, S. H., Al Alawi, M., McEnery, T., & McElvaney, N. G. Alpha 1 proteinase inhibitors for the treatment of alpha 1 antitrypsin deficiency: safety, tolerability, and patient outcomes. Ther. Clin. Risk Manag. 11, 143-151 (2015).
126. Casolaro, M. A., et al. Augmentation of lung antineutrophil elastase capacity with recombinant human alpha 1 antitrypsin. J. Appl. Physiol. (1985) 63, 2015-2023 (1987).
127. Hubbard, R. C., Brantly, M. L., Sellers, S. E., Mitchell, M. E., & Crystal, R. G. Anti-neutrophil-elastase defenses of the lower respiratory tract in α1 antitrypsin deficiency directly augmented with an aerosol of α1 antitrypsin. Ann. Intern. Med. 111, 206-212 (1989).
128. Franciosi, A. N., McCarthy, C., & McElvaney, N. G. The efficacy and safety of inhaled human α1 antitrypsin in people with α 1 antitrypsin deficiency-related emphysema. Expert Rev. Respir. Med. 9, 143-151 (2015).
129. Teckman, J. H., & Mangalat, N. Alpha 1 antitrypsin and liver disease: mechanisms of injury and novel interventions. Expert Rev. Gastroenterol. Hepatol. 9, 261-268 (2015).
130. Murray, K. F., & Carithers, R. L. Jr & ASSLD. AASLD practice guidelines: evaluation of the patient for liver transplantation. Hepatology 41, 1407-1432 (2005).
131. Tannuri, A. C., et al. Living related donor liver transplantation in children. Transplant. Proc. 43, 161-164 (2011).
132. Hughes, M. G. Jr et al. Long-term outcome in 42 pediatric liver transplant patients with alpha 1 antitrypsin deficiency: a single-center experience. Clin. Transplant. 25, 731-736 (2011).
133. Seersholm, N., & Kok Jensen, A. Survival in relation to lung function and smoking cessation in patients with severe hereditary alpha 1 antitrypsin deficiency. Am. J. Respir. Crit. Care Med. 151, 369-373 (1995).
134. Tanash, H. A., Nilsson, P. M., Nilsson, J. A., & Piitulainen, E. Clinical course and prognosis of never-smokers with severe alpha 1 antitrypsin deficiency (PiZZ). Thorax 63, 1091-1095 (2008).
135. Brantly, M. L., et al. Clinical features and history of the destructive lung disease associated with alpha 1 antitrypsin deficiency of adults with pulmonary symptoms. Am. Rev. Respir. Dis. 138, 327-336 (1988).
136. Stoller, J. K., et al. Mortality in individuals with severe deficiency of α1 antitrypsin: findings from the National Heart, Lung, and Blood Institute Registry. Chest 127, 1196-1204 (2005).
137. Campos, M. A., et al. Clinical characteristics of subjects with symptoms of α1-antitrypsin deficiency older than 60 years. Chest 135, 600-608 (2009).
138. Needham, M., & Stockley, R. A. α1 Antitrypsin deficiency. 3: clinical manifestations and natural history. Thorax 59, 441-445 (2004).
139. Dawkins, P. A., Dowson, L. J., Guest, P. J., & Stockley, R. A. Predictors of mortality in α1-antitrypsin deficiency. Thorax 58, 1020-1026 (2003).
140. Demeo, D. L., et al. Determinants of airflow obstruction in severe alpha 1 antitrypsin deficiency. Thorax 62, 806-813 (2007).
141. Holm, K. E., et al. Differences in adjustment between individuals with alpha 1 antitrypsin deficiency (AATD)-associated COPD and non-AATD COPD. COPD 10, 226-234 (2013).
142. Campos, M. A., Alazemi, S., Zhang, G., Wanner, A., & Sandhaus, R. A. Effects of a disease management program in individuals with alpha 1 antitrypsin deficiency. COPD 6, 31-40 (2009).
143. Dirksen, A., et al. Exploring the role of CT densitometry: a randomised study of augmentation therapy in α1-antitrypsin deficiency. Eur. Respir. J. 33, 1345-1353 (2009).
144. Rashid, S. T., et al. Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J. Clin. Invest. 120, 3127-3136 (2010).
145. Tafaleng, E. N., et al. Induced pluripotent stem cells model personalized variations in liver disease resulting from α1 antitrypsin deficiency. Hepatology 62, 147-157 (2015).
146. Dirksen, A., et al. A randomized clinical trial of α1-antitrypsin augmentation therapy. Am. J. Respir. Crit. Care Med. 160, 1468-1472 (1999).
147. Kaushal, S., et al. Rapamycin reduces intrahepatic alpha 1 antitrypsin mutant Z protein polymers and liver injury in a mouse model. Exp. Biol. Med. (Maywood) 235, 700-709 (2010).
148. Mahadeva, R., Dafforn, T. R., Carrell, R. W., & Lomas, D. A. 6 mer peptide selectively anneals to a pathogenic serpin conformation and blocks polymerization. Implications for the prevention of Z α1-antitrypsin-related cirrhosis. J. Biol. Chem. 277, 6771-6774 (2002).
149. Guo, S., et al. Antisense oligonucleotide treatment ameliorates alpha 1 antitrypsin-related liver disease in mice. J. Clin. Invest. 124, 251-261 (2014).
150. US National Library of Medicine. ClinicalTrials.gov https: //clinicaltrials.gov/ct2/show/NCT01379469 (2011).
151. Burrows, J. A., Willis, L. K., & Perlmutter, D. H. Chemical chaperones mediate increased secretion of mutant α1 antitrypsin (α1 AT) Z: a potential pharmacological strategy for prevention of liver injury and emphysema in α1 AT deficiency. Proc. Natl Acad. Sci. USA 97, 1796-1801 (2000).
152. Teckman, J. H. Lack of effect of oral 4 phenylbutyrate on serum alpha 1 antitrypsin in patients with alpha 1 antitrypsin deficiency: a preliminary study. J. Pediatr. Gastroenterol. Nutr. 39, 34-37 (2004).
153. Balch, W. E., Morimoto, R. I., Dillin, A., & Kelly, J. W. Adapting proteostasis for disease intervention. Science 319, 916-919 (2008).
154. Roth, D. M., et al. Modulation of the maladaptive stress response to manage diseases of protein folding. PLoS Biol. 12, e1001998 (2014).
155. Bouchecareilh, M., Hutt, D. M., Szajner, P., Flotte, T. R., & Balch, W. E. Histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA)-mediated correction of α1 antitrypsin deficiency. J. Biol. Chem. 287, 38265-38278 (2012).
156. Parfrey, H., Dafforn, T. R., Belorgey, D., Lomas, D. A., & Mahadeva, R. Inhibiting polymerization: new therapeutic strategies for Z α1-antitrypsin-related emphysema. Am. J. Respir. Cell Mol. Biol. 31, 133-139 (2004).
157. Nyon, M. P., & Gooptu, B. Therapeutic targeting of misfolding and conformational change in α1-antitrypsin deficiency. Future Med. Chem. 6, 1047-1065 (2014).
158. Chang, Y. P., et al. Targeting serpins in high-throughput and structure-based drug design. Methods Enzymol. 501, 139-175 (2011).
159. Chang, Y. P., Mahadeva, R., Chang, W. S., Lin, S. C., & Chu, Y. H. Small-molecule peptides inhibit Z α1-antitrypsin polymerization. J. Cell. Mol. Med. 13, 2304-2316 (2009).
160. Nyon, M. P., et al. An integrative approach combining ion mobility mass spectrometry, X ray crystallography, and nuclear magnetic resonance spectroscopy to study the conformational dynamics of α1-antitrypsin upon ligand binding. Protein Sci. 24, 1301-1312 (2015).
161. Gooptu, B., et al. Crystallographic and cellular characterisation of two mechanisms stabilising the native fold of α1-antitrypsin: implications for disease and drug design. J. Mol. Biol. 387, 857-868 (2009).
162. Mallya, M., et al. Small molecules block the polymerization of Z α1-antitrypsin and increase the clearance of intracellular aggregates. J. Med. Chem. 50, 5357-5363 (2007).
163. Patschull, A. O., Gooptu, B., Ashford, P., Daviter, T., & Nobeli, I. In silico assessment of potential druggable pockets on the surface of α1-antitrypsin conformers. PLoS ONE 7, e36612 (2012).
164. Loring, H. S., & Flotte, T. R. Current status of gene therapy for α 1 antitrypsin deficiency. Expert Opin. Biol. Ther. 15, 329-336 (2015).
165. Flotte, T. R., et al. Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing α1-antitrypsin: interim results. Hum. Gene Ther. 22, 1239-1247 (2011).
166. Chulay, J. D., et al. Preclinical evaluation of a recombinant adeno-associated virus vector expressing human alpha 1 antitrypsin made usinga recombinant herpes simplex virus production method. Hum. Gene Ther. 22, 155-165 (2011).
167. Brantly, M. L., et al. Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1 AAT gene therapy. Proc. Natl Acad. Sci. USA 106, 16363-16368 (2009).
168. Brantly, M. L., et al. Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 α1 antitrypsin (AAT) vector in AAT deficient adults. Hum. Gene Ther. 17, 1177-1186 (2006).
169. Liqun Wang, R., et al. Recombinant AAV serotype and capsid mutant comparison for pulmonary gene transfer of α 1 antitrypsin using invasive and noninvasive delivery. Mol. Ther. 17, 81-87 (2009).
170. Mueller, C., et al. Human Treg responses allow sustained recombinant adeno-associated virus-mediated transgene expression. J. Clin. Invest. 123, 5310-5318 (2013).
171. Ghaedi, M., Lotfi, A. S., & Soleimani, M. Establishment of lentiviral-vector-mediated model of human alpha 1 antitrypsin delivery into hepatocyte-like cells differentiated from mesenchymal stem cells. Tissue Cell 42, 181-189 (2010).
172. Argyros, O., et al. Persistent episomal transgene expression in liver following delivery of a scaffold/matrix attachment region containing non-viral vector. Gene Ther. 15, 1593-1605 (2008).
173. Chiuchiolo, M. J., et al. Phase I/II study of intrapleural administration of a serotype rh.10 replication-deficient adeno-associated virus gene transfer vector expressing the human alpha1 antitrypsin cDNA to individuals with α1 antitrypsin deficiency. Hum. Gene Ther. Clin. Dev. 25, 112-133 (2014).
174. Yusa, K., et al. Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells. Nature 478, 391-394 (2011).
175. Wilson, A. A., et al. Emergence of a stage-dependent human liver disease signature with directed differentiation of alpha 1 antitrypsin-deficient iPS cells. Stem Cell Rep. 4, 873-885 (2015).
176. Roussel, B. D., et al. Endoplasmic reticulum dysfunction in neurological disease. Lancet Neurol. 12, 105-118 (2013).
177. Griese, M., et al. α1-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients. Eur. Respir. J. 29, 240-250 (2007).
178. McElvaney, N. G., et al. Aerosol α1 antitrypsin treatment for cystic fibrosis. Lancet 337, 392-394 (1991).
179. Pahl, H. L., & Baeuerle, P. A. A novel signal transduction pathway from the endoplasmic reticulum to the nucleus is mediated by transcription factor NF kappa B. EMBO J. 14, 2580-2588 (1995).
180. Pahl, H. L., & Baeuerle, P. A. Expression of influenza virus hemagglutinin activates transcription factor NF ?B. J. Virol. 69, 1480-1484 (1995).
181. Sveger, T. The natural history of liver disease in α1 antitrypsin deficient children. Acta Paediatr. Scand. 77, 847-851 (1988).
182. Sveger, T., & Eriksson, S. The liver in adolescents with α1 antitrypsin deficiency. Hepatology 22, 514-517 (1995).
183. Sveger, T. α1 Antitrypsin deficiency in early childhood. Pediatrics 62, 22-25 (1978).
184. Eden, E., et al. Atopy, asthma, and emphysema in patients with severe α 1 antitrypysin deficiency. Am. J. Respir. Crit. Care Med. 156, 68-74 (1997).
185. Franciosi, A. N., McCarthy, C., Carroll, T. P., & McElvaney, N. G. Unusual acute sequelae of α1-antitrypsin deficiency: a myriad of symptoms with one common cure. Chest 148, e136-138 (2015).
186. Elzouki, A. N., Segelmark, M., Wieslander, J., & Eriksson, S. Strong link between the alpha1 antitrypsin PiZ allele and Wegener?s granulomatosis. J. Intern. Med. 236, 543-548 (1994).
187. Ciliberto, G., Dente, L., & Cortese, R. Cell-specific expression of a transfected human α1 antitrypsin gene. Cell 41, 531-540 (1985).
188. Rollini, P., & Fournier, R. E. Differential regulation of gene activity and chromatin structure within the human serpin gene cluster at 14q32.1 in macrophage microcell hybrids. Nucleic Acids Res. 28, 1767-1777 (2000).
189. Seersholm, N., et al. Does alpha1 antitrypsin augmentation therapy slow the annual decline in FEV1 in patients with severe hereditary alpha1 antitrypsin deficiency?. Wissenschaftliche Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen (WATL) alpha1 AT study group. Eur. Respir. J. 10, 2260-2263 (1997).
190. Lieberman, J. Augmentation therapy reduces frequency of lung infections in antitrypsin deficiency: a new hypothesis with supporting data. Chest 118, 1480-1485 (2000).
191. Wencker, M., Fuhrmann, B., Banik, N., Konietzko, N., & Wissenschaftliche Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen. Longitudinal follow up of patients with alpha1-protease inhibitor deficiency before and during therapy with IV α1-protease inhibitor. Chest 119, 737-744 (2001).
192. Tonelli, A. R., Rouhani, F., Li, N., Schreck, P., & Brantly, M. L. Alpha 1 antitrypsin augmentation therapy in deficient individuals enrolled in the Alpha 1 Foundation DNA and Tissue Bank. Int. J. Chron. Obstruct Pulmon Dis. 4, 443-452 (2009