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Lupus • February 2012<br />

Induction of the ‘ASIA’ syndrome<br />

in NZB/NZWF1 mice after injection of<br />

complete Freund’s adjuvant (CFA)<br />

Author information<br />

Bassi N1, Luisetto R, Del Prete D,<br />

Ghirardello A, Ceol M, Rizzo S, Iaccarino L,<br />

Gatto M, Valente ML, Punzi L, Doria A.<br />

Division of Rheumatology<br />

Department of Clinical and Experimental Medicine<br />

University of Padova, Italy<br />

Abstract<br />

Adjuvants, commonly used in vaccines, may be responsible for inducing<br />

autoimmunity and autoimmune diseases, both in humans and mice.<br />

The so-called ‘ASIA’ (Autoimmune/inflammatory Syndrome Induced<br />

by Adjuvants) syndrome has been recently described, which is caused<br />

by the exposure to a component reproducing the effect of adjuvants.<br />

The aim of our study was to evaluate the effect of injection of complete<br />

Freund’s adjuvant (CFA) in NZB/NZWF1 mice, a lupus-prone<br />

murine model. We injected 10 NZB/NZWF1 mice with CFA/PBS and<br />

10 with PBS, three times, 3 weeks apart, and followed-up until natural<br />

death. CFA-injected mice developed both anti-double-stranded DNA<br />

and proteinuria earlier and at higher levels than the control group. Proteinuria-free<br />

survival rate and survival rate were significantly lower in<br />

CFA-treated mice than in the control mice (p = 0.002 and p = 0.001,<br />

respectively). Histological analyses showed a more severe glomerulonephritis<br />

in CFA-injected mice compared with the control mice. In<br />

addition, lymphoid hyperplasia in spleen and lungs, myocarditis, and<br />

vasculitis were observed in the former, but not in the latter group. In<br />

conclusion, the injection of CFA in NZB/NZWF1 mice accelerated autoimmune<br />

manifestations resembling ‘ASIA’ syndrome in humans.<br />

“... lymphoid hyperplasia in spleen and lungs,<br />

myocarditis, and vasculitis were observed in the former,<br />

but not in the latter group. In conclusion, the injection of<br />

Complete Freund’s Adjuvant (CFA) [a vaccine ingredient]<br />

in NZB/NZWF1 mice accelerated autoimmune manifestations<br />

resembling ‘ASIA’ syndrome in humans.”<br />

[complete Freund’s adjuvant is used in some vaccines]<br />

http://www.ncbi.nlm.nih.gov/pubmed/22235054

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