Vaccines, administered to animal and humans, are clearly one of the best achievements of modern medicine and are commonly and safely inoculated to the vast majority of subjects. However in rare occasions vaccines may induce autoimmune or auto-inflammatory conditions both in animals and in humans . These conditions, either defined diseases such as Gullian Barre syndrome or enigmatic ones, have been reported following different vaccines and vaccination protocols. The susceptibility factors and the temporal association between vaccines and these rare immune mediated reactions are yet to be defined, however the similarities between vaccines and infections and the addition of an adjuvant (i.e. alum, squalene etc.) to almost every vaccine are considered major contributors to such adverse events. Perhaps the most evaluated condition is MMF, in which a cause was clearly delineated. MMF is a rare condition caused by deposition of alum, used to adjuvant different vaccines, which bring about an immune mediated muscles disease . The discrepancy between the wide application of aluminum hydroxide and the rarity of MMF was resolved by the observations that alum may trigger MMF in genetically susceptible subjects carrying the HLA–DRB1*01 . Thus, in only a minority of genetically prone patients alum may induce this syndrome.
A common denominator to each of these four syndromes as well as to various infectious agents is the trigger entailing adjuvant activity. Adjuvants are commonly used in medicine to augment an immune response to treatments such as the protective response induced by vaccines and were considered to be inert. Nalp3 inflammasome system. Moreover adjuvants enhance adaptive immune responses via inducing Th2 cell activation as well as chemokines and cytokines secretion thus helping the recruitment of B and T cells [4–6]. as well as inducing the secretion of Il-17 . Alas, studies of animal models and humans demonstrated the ability of some of these adjuvants to inflict an immune mediated disease and even autoimmunity by themselves .
Thus, herein we will describe the syndrome entitled the “Autoimmune (Auto-inflammatory) Syndrome induced by adjuvants” (ASIA) . We will also delineate who is at risk of developing autoimmune conditions upon exposure to adjuvants .
Agmon-Levin N, Paz Z, Israeli E, Shoenfeld Y. Vaccines and autoimminty. Nat Rev Rheumatol. 2009; 5: 648–52.
Gherardi RK, Coquet M, Cherin P, Belec L, Moretto P, Dreyfus PA, Pellissier JF, Chariot P, Authier FJ. Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminium hydroxide in muscle. Brain 2001 Sep;124(Pt 9):1821–31.
Guis S, Pellissier JF, Nicoli F, Reviron D, Mattei JP, Gherardi RK, Pelletier J, Kaplanski G, Figarella-Branger D, Roudier J.HLA-DRB1*01 and macrophagic myofasciitis. Arthritis Rheum. 2002; 46: 2535–7.
Kool M, Soullié T, van Nimwegen M, Willart MA, Muskens F, Jung S, Hoogsteden HC, Hammad H, Lambrecht BN.Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. J Exp Med. 2008; 205: 869–82.
Eisenbarth SC, Colegio OR, O'Connor W, Sutterwala FS, Flavell RA. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature 2008; 453: 1122–1126.
Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, Rock KL, Fitzgerald KA, Latz E.Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 2008; 9: 847–56
Wolfram D, et al. T-regulatory cells and Th17 cells in peri-silicone implants capsular fibrosis. Plastic & Reconstructive Surgery 2012; 129: 327–37.
Agmon-Levin N, Arango MT, Kivity S, Katzav A,Gilburd B, Blank M, Tomer N, Volkov A, Barshack I, Chapman J, Shoenfeld Y. Immunization with hepatitis B vaccine accelerates SLE-like disease in a murine model. Journal of Autoimmunity 2014; 54: 21e32.
Perricone C, Colafrancesco S, Mazor RD, Soriano A, Agmon-Levin N, Shoenfeld Y. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA). 2013: Unveiling the pathogenic, clinical and diagnostic aspects. Journal of Autoimmunity 2013; 47: 1–16.
Soriano A, Nesher G, Shoenfeld Y. Predicting post-vaccination autoimmunity: Who might be at risk? Pharmacol Res. 2015; 92C:18–22.
Disclosure of Interest None declared
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