Intravenous immunoglobulins for Alzheimer's disease

Current Alzheimer Research

Volumn 11, Issue 7, 2014, Pages 626-636

  Puli, Lakshman ^a   Tanila, Heikki ^b,c   Relkin, Norman ^a  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

^b UNIVERSITY OF EASTERN FINLAND   (Finland)

^c KUOPIO UNIVERSITY HOSPITAL   (Finland)

Author keywords

Alzheimer's disease; Amyloid beta; Antibodies; Human intravenous immunoglobulins; IgG sialylation; Immunomodulation; Microglia; Neurogenesis; Neuroinflammation; Oligomers

Indexed keywords

AMYLOID BETA PROTEIN; IMMUNOGLOBULIN; IMMUNOGLOBULIN G; PLACEBO; TAU PROTEIN; IMMUNOLOGIC FACTOR; AMYLOID BETA PROTEIN ANTIBODY; APOLIPOPROTEIN E4;

ALZHEIMER DISEASE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BINDING AFFINITY; BIOLOGICAL ACTIVITY; DRUG HALF LIFE; DRUG MECHANISM; HUMAN; IMMUNOMODULATION; NERVOUS SYSTEM DEVELOPMENT; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PRIORITY JOURNAL; SIALYLATION; SIGNAL TRANSDUCTION; ANIMAL; CLINICAL TRIAL (TOPIC); IMMUNOLOGY; CLINICAL STUDY; EXPERIMENTAL STUDY; HIPPOCAMPUS; MULTICENTER STUDY (TOPIC); PATIENT SAFETY; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC);

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; CLINICAL TRIALS AS TOPIC; HUMANS; IMMUNOGLOBULINS, INTRAVENOUS; IMMUNOLOGIC FACTORS;

EID: 84906896007     PISSN: 15672050     EISSN: 18755828     Source Type: Journal    
DOI: 10.2174/1567205011666140812113415     Document Type: Article

References (101)

1. Alzheimer's Association, Thies W, Bleiler L. 2011 Alzheimer's disease facts and figures. Alzheimers Dement 7(2): 208-244 (2011).
2. Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol Sci 12(10): 383-388 (1991).
3. Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science 256(5054): 184-185 (1992).
4. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297(5580): 353-356 (2002).
5. Mucke L, Selkoe DJ. Neurotoxicity of Amyloid beta-Protein: Synaptic and Network Dysfunction. Cold Spring Harb Perspect Med 2(7): a006338 (2012).
6. Jack CR, Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 12(2): 207-216 (2013).
7. Iqbal K, McLachlan DRC, Winblad B, Wisniewski HW Eds, Alzheimer's Disease: Basic Mechanisms, Diagnosis and Therapeutic Strategies. New York, Wiley. 1991.
8. Gaskin F, Finley J, Fang Q, Xu S, Fu SM. Human antibodies reactive with beta-amyloid protein in Alzheimer's disease. J Exp Med 177(4): 1181-1186 (1993).
9. Hyman BT, Smith C, Buldyrev I, Whelan C, Brown H, Tang MX, et al. Autoantibodies to amyloid-beta and Alzheimer's disease. Ann Neurol 49(6): 808-810 (2001).
10. Song MS, Mook-Jung I, Lee HJ, Min JY, Park MH. Serum antiamyloid-beta antibodies and Alzheimer's disease in elderly Korean patients. J Int Med Res 35(3): 301-306 (2007).
11. Yang ZY, Wang HQ, Yao ZB. Age-associated changes of antibodies against [beta]-amyloid protein in plasma of healthy Chinese population. J Sun Yat-sen Univ (Med Sci) 26: 125 (2005).
12. Weksler ME, Relkin N, Turkenich R, LaRusse S, Zhou L, Szabo P. Patients with Alzheimer disease have lower levels of serum antiamyloid peptide antibodies than healthy elderly individuals. Exp Gerontol 37(7): 943-948 (2002).
13. Du Y, Dodel R, Hampel H, Buerger K, Lin S, Eastwood B, et al. Reduced levels of amyloid beta-peptide antibody in Alzheimer disease. Neurology 57(5):801-805 (2001).
14. Szabo P, Mujalli DM, Rotondi ML, Sharma R, Weber A, Schwarz HP, et al. Measurement of anti-beta amyloid antibodies in human blood. J Neuroimmunol 227(1-2):167-174 (2010).
15. Klaver AC, Patrias LM, Coffey MP, Finke JM, Loeffler DA. Measurement of anti-Abeta1-42 antibodies in intravenous immunoglobulin with indirect ELISA: the problem of nonspecific binding. J Neurosci Methods 187(2): 263-269 (2010).
16. Glabe CG. Conformation-dependent antibodies target diseases of protein misfolding. Trends Biochem Sci 29(10): 542-547 (2004).
17. O'Nuallain B, Williams AD, McWilliams-Koeppen HP, Acero L, Weber A, Ehrlich H, et al. Anti-amyloidogenic activity of IgGs contained in normal plasma. J Clin Immunol 30(1): S37-42 (2010).
18. Welzel AT, Williams AD, McWilliams-Koeppen HP, Acero L, Weber A, Blinder V, et al. Human anti-Abeta IgGs target conformational epitopes on synthetic dimer assemblies and the AD brainderived peptide. PLoS One 7(11): e50317 (2012).
19. Moir RD, Tseitlin KA, Soscia S, Hyman BT, Irizarry MC, Tanzi RE. Autoantibodies to redox-modified oligomeric Abeta are attenuated in the plasma of Alzheimer's disease patients. J Biol Chem 280(17): 17458-17463 (2005).
20. Henkel AW, Dittrich PS, Groemer TW, Lemke EA, Klingauf J, Klafki HW, et al. Immune complexes of auto-antibodies against A beta 1-42 peptides patrol cerebrospinal fluid of non-Alzheimer's patients. Mol Psychiatry 12(6): 601-610 (2007).
21. Kellner A, Matschke J, Bernreuther C, Moch H, Ferrer I,Glatzel M. Autoantibodies against beta-amyloid are common in Alzheimer's disease and help control plaque burden. Ann Neurol 65(1): 24-31 (2009).
22. Britschgi M, Olin CE, Johns HT, Takeda-Uchimura Y, LeMieux MC, Rufibach K, et al. Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease. Proc Natl Acad Sci USA 106(29): 12145-12150 (2009).
23. Martin TD. IGIV: contents, properties, and methods of industrial production--evolving closer to a more physiologic product. Int Immunopharmacol 6(4):517-522 (2006).
24. Radosevich M, Burnouf T. Intravenous immunoglobulin G: trends in production methods, quality control and quality assurance. Vox Sang 98(1):12-28 (2010).
25. Reipert BM, Ilas J, Carnewal C, Fureder SF, Bolzlbauer U, Teschner W, et al. Fc function of a new intravenous immunoglobulin product: IGIV 10% triple virally inactivated solution. Vox Sang 91(3): 256-263 (2006).
26. Nimmerjahn F, Ravetch JV. Anti-inflammatory actions of intravenous immunoglobulin. Annu Rev Immunol 26: 513-533 (2008).
27. Boros P, Gondolesi G, Bromberg JS. High dose intravenous immunoglobulin treatment: mechanisms of action. Liver Transpl 11(12):1469-1480 (2005).
28. St-Amour I, Bousquet M, Pare I, Drouin-Ouellet J, Cicchetti F, Bazin R, et al. Impact of intravenous immunoglobulin on the dopaminergic system and immune response in the acute MPTP mouse model of Parkinson's disease. J Neuroinflammation 9: 234-2094-9-234 (2012).
29. Spurlock NK, Prittie JE. A review of current indications, adverse effects, and administration recommendations for intravenous immunoglobulin. J Vet Emerg Crit Care (San Antonio) 21(5): 471-483 (2011).
30. Ryan ME, Webster ML, Statler JD. Adverse effects of intravenous immunoglobulin therapy. Clin Pediatr (Phila) 35(1): 23-31 (1996).
31. Cheng MJ, Christmas C. Special considerations with the use of intravenous immunoglobulin in older persons. Drugs Aging 28(9): 729-736 (2011).
32. Orbach H, Katz U, Sherer Y, Shoenfeld Y. Intravenous immunoglobulin: adverse effects and safe administration. Clin Rev Allergy Immunol 29(3): 173-184 (2005).
33. Kaveri SV, Maddur MS, Hegde P, Lacroix-Desmazes S, Bayry J. Intravenous immunoglobulins in immunodeficiencies: more than mere replacement therapy. Clin Exp Immunol 164(2): 2-5 (2011).
34. Ballow M. Clinical and investigational considerations for the use of IGIV therapy. Am J Health Syst Pharm 62(16 Suppl 3): S12-8; quiz S19-21 (2005).
35. Szabo P, Relkin N, Weksler ME. Natural human antibodies to amyloid beta peptide. Autoimmun Rev 7(6): 415-420 (2008).
36. Dodel R, Balakrishnan K, Keyvani K, Deuster O, Neff F, AndreiSelmer LC, et al. Naturally occurring autoantibodies against betaamyloid: investigating their role in transgenic animal and in vitro models of Alzheimer's disease. J Neurosci 31(15): 5847-5854 (2011).
37. O'Nuallain B, Hrncic R, Wall JS, Weiss DT, Solomon A. Diagnostic and therapeutic potential of amyloid-reactive IgG antibodies contained in human sera. J Immunol 176(11): 7071-7078 (2006).
38. Fillit H, Hess G, Hill J, Bonnet P, Toso C. IV immunoglobulin is associated with a reduced risk of Alzheimer disease and related disorders. Neurology 73(3): 180-185 (2009).
39. Dodel R, Hampel H, Depboylu C, Lin S, Gao F, Schock S, et al. Human antibodies against amyloid beta peptide: a potential treatment for Alzheimer's disease. Ann Neurol 52(2): 253-256 (2002).
40. Dodel RC, Du Y, Depboylu C, Hampel H, Frolich L, Haag A, et al. Intravenous immunoglobulins containing antibodies against betaamyloid for the treatment of Alzheimer's disease. J Neurol Neurosurg Psychiatry 75(10): 1472-1474 (2004).
41. Relkin NR, Szabo P, Adamiak B, Burgut T, Monthe C, Lent RW, et al. 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol Aging 30(11): 1728-1736 (2009).
42. Devi G, Schultz S, Khosrowshahi L, Agnew A, Olali E, Devi G. A retrospective chart review of the tolerability and efficacy of intravenous immunoglobulin in the treatment of Alzheimer's disease. J Am Geriatr Soc 56(4): 772-774 (2008).
43. Relkin N, Moore D, Tsakanikas D, Brewer J. Intravenous Immunoglobulin treatment decreases ventricular enlargement and cognitive decline in Alzheimer's disease. Neurology 75: 380 (2010).
44. N. Relkin. Alzheimer's Treatment Study Reports Three Years with No Decline in Memory and Function at AAIC 2012 http://www.alz.org/_aaic2013/releases/tues_1030amct_ivig_trial.asp (02/10,2014).
45. Dodel R, Rominger A, Bartenstein P, Barkhof F, Blennow K, Forster S, et al. Intravenous immunoglobulin for treatment of mild-tomoderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial. Lancet Neurol 12(3): 233-243 (2013).
46. Relkin N. Clinical Trials of Intravenous Immunoglobulin for Alzheimer's Disease. J Clin Immunol (2014).
47. Lemere CA. Immunotherapy for Alzheimer's disease: hoops and hurdles. Mol Neurodegener 8(1): 36-1326-8-36 (2013).
48. Check E. Battle of the mind. Nature 422(6930): 370-372 (2003).
49. Das P, Murphy MP, Younkin LH, Younkin SG, Golde TE. Reduced effectiveness of Abeta1-42 immunization in APP transgenic mice with significant amyloid deposition. Neurobiol Aging 22(5): 721-727 (2001).
50. Proulx DP, Rouleau P, Pare I, Vallieres-Noel MM and Bazin R. Interaction between intravenous immunoglobulin (IVIg) and the low-density lipoprotein receptor-related protein 1: A role for transcytosis across the blood brain barrier? J Neuroimmunol 251(1-2): 39-44 (2012).
51. Boado RJ, Zhang Y, Zhang Y, Xia CF, Pardridge WM. Fusion antibody for Alzheimer's disease with bidirectional transport across the blood-brain barrier and abeta fibril disaggregation. Bioconjug Chem 18(2): 447-455 (2007).
52. Deane R, Sagare A, Hamm K, Parisi M, LaRue B, Guo H, et al. IgG-assisted age-dependent clearance of Alzheimer's amyloid beta peptide by the blood-brain barrier neonatal Fc receptor. J Neurosci 25(50): 11495-11503 (2005).
53. Winkler DT, Abramowski D, Danner S, Zurini M, Paganetti P, Tolnay M, et al. Rapid cerebral amyloid binding by Abeta antibodies infused into beta-amyloid precursor protein transgenic mice. Biol Psychiatry 68(10): 971-974 (2010).
54. Levites Y, Smithson LA, Price RW, Dakin RS, Yuan B, Sierks MR, et al. Insights into the mechanisms of action of anti-Abeta antibodies in Alzheimer's disease mouse models. FASEB J 20(14): 2576-2578 (2006).
55. Du Y, Wei X, Dodel R, Sommer N, Hampel H, Gao F, et al. Human anti-beta-amyloid antibodies block beta-amyloid fibril formation and prevent beta-amyloid-induced neurotoxicity. Brain 126(Pt 9): 1935-1939 (2003).
56. Istrin G, Bosis E,Solomon B. Intravenous immunoglobulin enhances the clearance of fibrillar amyloid-beta peptide. J Neurosci Res 84(2): 434-443 (2006).
57. Magga J, Puli L, Pihlaja R, Kanninen K, Neulamaa S, Malm T, et al. Human intravenous immunoglobulin provides protection against Abeta toxicity by multiple mechanisms in a mouse model of Alzheimer's disease. J Neuroinflammation 7(1): 90 (2010).
58. Widiapradja A, Vegh V, Lok KZ, Manzanero S, Thundyil J, Gelderblom M, et al. Intravenous immunoglobulin protects neurons against amyloid beta-peptide toxicity and ischemic stroke by attenuating multiple cell death pathways. J Neurochem 122(2): 321-32. (2012).
59. Counts SE, Ray B, Mufson EJ, Perez SE, He B, Lahiri DK. Intravenous Immunoglobulin (IVIG) Treatment Exerts Antioxidant and Neuropreservatory Effects in Preclinical Models of Alzheimer's Disease. J Clin Immunol 34(1): S80-5 (2014).
60. Overdijk MB, Verploegen S, Ortiz Buijsse A, Vink T, Leusen JH, Bleeker WK, et al. Crosstalk between human IgG isotypes and murine effector cells. J Immunol 189(7): 3430-3438 (2012).
61. Bard F, Fox M, Friedrich S, Seubert P, Schenk D, Kinney GG, et al. Sustained levels of antibodies against Abeta in amyloid-rich regions of the CNS following intravenous dosing in human APP transgenic mice. Exp Neurol 238(1): 38-43 (2012).
62. St-Amour I, Pare I, Alata W, Coulombe K, Ringuette-Goulet C, Drouin-Ouellet J, et al. Brain bioavailability of human intravenous immunoglobulin and its transport through the murine blood-brain barrier. J Cereb Blood Flow Metab 33(12): 1983-1992 (2013).
63. Puli Lk. Experimental immunomodulation in Alzheimer's disease. PhD dissertation. Kuopio: University of Eastern Finland 2012.
64. Puli L, Pomeshchik Y, Olas K, Malm T, Koistinaho J, Tanila H. Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer's disease. J Neuroinflammation 9: 105 (2012).
65. Mengel D, Roskam S, Neff F, Balakrishnan K, Deuster O, Gold M, et al. Naturally occurring autoantibodies interfere with betaamyloid metabolism and improve cognition in a transgenic mouse model of Alzheimer's disease 24 h after single treatment. Transl Psychiatry 3: e236 (2013).
66. Roher AE, Cribbs DH, Kim RC, Maarouf CL, Whiteside CM, Kokjohn TA, et al. Bapineuzumab alters abeta composition: implications for the amyloid cascade hypothesis and anti-amyloid immunotherapy. PLoS One 8(3): e59735 (2013).
67. Maarouf CL, Daugs ID, Kokjohn TA, Kalback WM, Patton RL, Luehrs DC, et al. The biochemical aftermath of anti-amyloid immunotherapy. Mol Neurodegener 5: 39-1326-5-39 (2010).
68. Kemppainen S, Rantamaki T, Jeronimo-Santos A, Lavasseur G, Autio H, Karpova N, et al. Impaired TrkB receptor signaling contributes to memory impairment in APP/PS1 mice. Neurobiol Aging 33(6): 1122.e23-1122.e39 (2012).
69. St-Amour I, Paré I, Tremblay C, Calon F, Bazin R. Beneficial effects of IVIg in the triple transgenic mouse model of Alzheimer's disease. Alzheimers Dement 8(4): P576 (2012).
70. Knight E, Szabo P, Ehrlich M, Relkin N, Gandy S. Neat, but not beta-amyloidâ "affinity-depleted, Baxter Immune Globulin® modulates behavior in transgenic mouse expressing Dutch betaamyloid oligomers. Alzheimers Dement 9(4): P885 (2013).
71. Pfeifer M, Boncristiano S, Bondolfi L, Stalder A, Deller T, Staufenbiel M, et al. Cerebral hemorrhage after passive anti-Abeta immunotherapy. Science 298(5597): 1379 (2002).
72. Lemere CA, Masliah E. Can Alzheimer disease be prevented by amyloid-beta immunotherapy? Nat Rev Neurol 6(2):108-119 (2010).
73. Sudduth TL, Greenstein A, Wilcock DM. Intracranial injection of Gammagard, a human IVIg, modulates the inflammatory response of the brain and lowers Abeta in APP/PS1 mice along a different time course than anti-Abeta antibodies. J Neurosci 33(23): 9684-9692 (2013).
74. Butovsky O, Ziv Y, Schwartz A, Landa G, Talpalar AE, Pluchino S, et al. Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol Cell Neurosci 31(1): 149-160 (2006).
75. Ziv Y, Ron N, Butovsky O, Landa G, Sudai E, Greenberg N, et al. Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci 9(2): 268-275 (2006).
76. Kaneko N, Kudo K, Mabuchi T, Takemoto K, Fujimaki K, Wati H, et al. Suppression of cell proliferation by interferon-alpha through interleukin-1 production in adult rat dentate gyrus. Neuropsychopharmacology 31(12):2619-2626 (2006).
77. Vallieres L, Campbell IL, Gage FH, Sawchenko PE. Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. J Neurosci 22(2): 486-492 (2002).
78. Koo JW, Duman RS. IL-1beta is an essential mediator of the antineurogenic and anhedonic effects of stress. Proc Natl Acad Sci USA 105(2): 751-756 (2008).
79. Iosif RE, Ekdahl CT, Ahlenius H, Pronk CJ, Bonde S, Kokaia Z, et al. Tumor necrosis factor receptor 1 is a negative regulator of progenitor proliferation in adult hippocampal neurogenesis. J Neurosci 26(38): 9703-9712 (2006).
80. van der Borght K, Kohnke R, Goransson N, Deierborg T, Brundin P, Erlanson-Albertsson C, et al. Reduced neurogenesis in the rat hippocampus following high fructose consumption. Regul Pept 167(1): 26-30 (2011).
81. Ekdahl CT, Claasen JH, Bonde S, Kokaia Z, Lindvall O. Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci USA 100(23): 13632-13637 (2003).
82. Monje ML, Toda H, Palmer TD. Inflammatory blockade restores adult hippocampal neurogenesis. Science 302(5651): 1760-1765 (2003).
83. Arumugam TV, Tang SC, Lathia JD, Cheng A, Mughal MR, Chigurupati S, et al. Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke by preventing complementmediated neuronal cell death. Proc Natl Acad Sci USA 104(35): 14104-14109 (2007).
84. Bachstetter AD, Norris CM, Sompol P, Wilcock DM, Goulding D, Neltner JH, et al. Early stage drug treatment that normalizes proinflammatory cytokine production attenuates synaptic dysfunction in a mouse model that exhibits age-dependent progression of Alzheimer's disease-related pathology. J Neurosci 32(30): 10201-10210 (2012).
85. Olsson B, Hertze J, Lautner R, Zetterberg H, Nagga K, Hoglund K, et al. Microglial Markers are Elevated in the Prodromal Phase of Alzheimer's Disease and Vascular Dementia. J Alzheimers Dis 33(1): 45-53 (2013).
86. Owen DR, Matthews PM. Imaging brain microglial activation using positron emission tomography and translocator proteinspecific radioligands. Int Rev Neurobiol 101: 19-39 (2011).
87. Sierra A, Encinas JM, Maletic-Savatic M. Adult human neurogenesis: from microscopy to magnetic resonance imaging. Front Neurosci 5: 47 (2011).
88. Anthony RM, Wermeling F, Ravetch JV. Novel roles for the IgG Fc glycan. Ann NY Acad Sci 1253: 170-180 (2012).
89. Samuelsson A, Towers TL, Ravetch JV. Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor. Science 291(5503): 484-486 (2001).
90. Kaneko Y, Nimmerjahn F, Ravetch JV. Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 313(5787): 670-673 (2006).
91. Anthony RM, Wermeling F, Karlsson MC, Ravetch JV. Identification of a receptor required for the anti-inflammatory activity of IVIG. Proc Natl Acad Sci USA 105(50): 19571-19578 (2008).
92. Anthony RM, Kobayashi T, Wermeling F, Ravetch JV. Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway. Nature 475(7354): 110-113 (2011).
93. Schwab I, Seeling M, Biburger M, Aschermann S, Nitschke L, Nimmerjahn F. B cells and CD22 are dispensable for the immediate antiinflammatory activity of intravenous immunoglobulins in vivo. Eur J Immunol 42(12): 3302-9 (2012).
94. Schwab I, Biburger M, Kronke G, Schett G, Nimmerjahn F. IVIgmediated amelioration of ITP in mice is dependent on sialic acid and SIGNR1. Eur J Immunol 42(4): 826-830 (2012).
95. Kasermann F, Boerema DJ, Ruegsegger M, Hofmann A, Wymann S, Zuercher AW, et al. Analysis and functional consequences of increased Fab-sialylation of intravenous immunoglobulin (IVIG) after lectin fractionation. PLoS One 7(6): e37243 (2012).
96. Stadlmann J, Weber A, Pabst M, Anderle H, Kunert R, Ehrlich HJ, et al. A close look at human IgG sialylation and subclass distribution after lectin fractionation. Proteomics 9(17): 4143-4153 (2009).
97. Guhr T, Bloem J, Derksen NI, Wuhrer M, Koenderman AH, Aalberse RC, et al. Enrichment of sialylated IgG by lectin fractionation does not enhance the efficacy of immunoglobulin G in a murine model of immune thrombocytopenia. PLoS One 6(6): e21246 (2011).
98. Leontyev D, Katsman Y, Ma XZ, Miescher S, Kasermann F, Branch DR. Sialylation-independent mechanism involved in the amelioration of murine immune thrombocytopenia using intravenous gammaglobulin. Transfusion 52(8): 1799-1805 (2012).
99. Lundstrom SL, Yang H, Lyutvinskiy Y, Rutishauser D, Herukka SK, Soininen H, et al. Blood plasma IgG Fc glycans are significantly altered in Alzheimer's disease and progressive mild cognitive impairment. J Alzheimers Dis 38(3): 567-579 (2014).
100. Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B, et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood 112(2): 277-286 (2008).
101. Bayry J, Kazatchkine MD, Kaveri SV. Shortage of human intravenous immunoglobulin--reasons and possible solutions. Nat Clin Pract Neurol 3(3): 120-121 (2007).