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* Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, Ullevålsveien 72, Oslo, Norway;
Department of Oral Biology, University of Florida, Gainesville, FL, 32610-0424;
Analytical Toxicology Core Laboratory, Department of Physiological Sciences, University of Florida, Gainesville, FL 32610;
Department of Laboratory Medicine, Division of Pathology, Iwase General Hospital, Sukagawa, Fukushima, Japan;
¶ Department of Pathology, Matsudo Municipal Hospital, Matsudo, Chiba, Japan;
|| Department of Clinical Medicine, Immunology and Infectious Diseases, Faculty of Medicine, University of Bari, Policlinico, Bari, Italy;
# EWOS Innovation, Dirdal, Norway;
** Fiskehelsa BA, Valsøyfjord, Norway; and
Division of Rheumatology and Clinical Immunology, Department of Medicine, and Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610-0221
Over half of the salmon consumed globally are farm-raised. The introduction of oil-adjuvanted vaccines into salmon aquaculture made large-scale production feasible by preventing infections. The vaccines that are given i.p. contain oil adjuvant such as mineral oil. However, in rodents, a single i.p. injection of adjuvant hydrocarbon oil induces lupus-like systemic autoimmune syndrome, characterized by autoantibodies, immune complex glomerulonephritis, and arthritis. In the present study, whether the farmed salmon that received oil-adjuvanted vaccine have autoimmune syndrome similar to adjuvant oil-injected rodents was examined. Sera and tissues were collected from vaccinated or unvaccinated Atlantic salmon (experimental, seven farms) and wild salmon. Autoantibodies (immunofluorescence, ELISA, and immunoprecipitation) and IgM levels (ELISA) in sera were measured. Kidneys and livers were examined for pathology. Autoantibodies were common in vaccinated fish vs unvaccinated controls and they reacted with salmon cells/Ags in addition to their reactivity with mammalian Ags. Diffuse nuclear/cytoplasmic staining was common in immunofluorescence but some had more specific patterns. Serum total IgM levels were also increased in vaccinated fish; however, the fold increase of autoantibodies was much more than that of total IgM. Sera from vaccinated fish immunoprecipitated ferritin and 
50% also reacted with other unique proteins. Thrombosis and granulomatous inflammation in liver, and immune-complex glomerulonephritis were common in vaccinated fish. Autoimmunity similar to the mouse model of adjuvant oil-induced lupus is common in vaccinated farmed Atlantic salmon. This may have a significant impact on production loss, disease of previously unknown etiology, and future strategies of vaccines and salmon farming.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Current address: National Institute of Gastroenterology, Castellana Grotte, Italy.
2 Current address: Innovasjon Norge, Postboks 665, 4666 Kristiansand, Norway.
3 Address correspondence and reprint requests to Dr. Minoru Satoh, Division of Rheumatology and Clinical Immunology, University of Florida, ARB R2-156, 1600 SW Archer Road, P.O.Box 100221, Gainesville, FL 32610. E-mail address: satohm{at}medicine.ufl.edu
4 Abbreviations used in this paper: ANA, antinuclear Ab; snRNP, small nuclear ribonucleoprotein; IF, immunofluorescence; IPP, immunoprecipitation; PAS, periodic acid-Schiff; MSB, Martius scarlet blue; EM, electron microscopy; ds, double-stranded; ss, single-stranded; RF, rheumatoid factor; GBM, glomerular basement membrane; I-IFN, type I interferon.
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