Immunologic Research

, Volume 65, Issue 1, pp 150–156 | Cite as

Are the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and the undifferentiated connective tissue disease (UCTD) related to each other? A case-control study of environmental exposures

  • F. Scanzi
  • L. Andreoli
  • M. Martinelli
  • M. Taraborelli
  • I. Cavazzana
  • N. Carabellese
  • R. Ottaviani
  • F. Allegri
  • F. Franceschini
  • N. Agmon-Levin
  • Y. Shoenfeld
  • Angela Tincani
Environment and Autoimmunity

Abstract

The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is an entity that includes different autoimmune conditions observed after exposure to an adjuvant. Patients with undifferentiated connective tissue disease (UCTD) present many signs and symptoms of ASIA, alluding to the idea that an exposure to adjuvants can be a trigger also for UCTD. The aim of this case-control study was to investigate exposure to adjuvants prior to disease onset in patients affected by UCTD. Ninety-two UCTD patients and 92 age- and sex-matched controls with no malignancy, chronic infections, autoimmune disease nor family history of autoimmune diseases were investigated for exposure to adjuvants. An ad hoc-created questionnaire exploring the exposure to vaccinations, foreign materials and environmental and occupational exposures was administered to both cases and controls. Autoantibodies were also analyzed (anti-nuclear, anti-extractable nuclear antigens, anti-double-stranded DNA, anti-cardiolipin, anti-β2 glycoprotein I). UCTD patients displayed a greater exposure to HBV (p = 0.018) and tetanus toxoid (p < 0.001) vaccinations, metal implants (p < 0.001), cigarette smoking (p = 0.006) and pollution due to metallurgic factories and foundries (p = 0.048) as compared to controls. UCTD patients exposed to major ASIA triggers (vaccinations, silicone implants) (n = 49) presented more frequently with chronic fatigue (p < 0.001), general weakness (p = 0.011), irritable bowel syndrome (p = 0.033) and a family history for autoimmunity (p = 0.018) in comparison to non-exposed UCTDs. ASIA and UCTD can be considered as related entities in the “mosaic of autoimmunity”: the genetic predisposition and the environmental exposure to adjuvants elicit a common clinical phenotype characterized by signs and symptoms of systemic autoimmunity.

Keywords

Adjuvants ASIA syndrome Undifferentiated connective tissue disease Vaccinations Metal implants 

Notes

Acknowledgements

The authors wish to acknowledge the kind collaboration of Dr. Lucia Cretti and Dr. Mirella Marini (Department of Transfusion Medicine, Spedali Civili, Brescia) in the enrollment of healthy blood donors.

Thanks to all the patients and control individuals participating to the study.

Compliance with ethical standards

The study was approved by the local Ethic Committee in Brescia and performed in accordance to the good clinical practice and to the Declaration of Helsinki.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • F. Scanzi
    • 1
  • L. Andreoli
    • 1
  • M. Martinelli
    • 1
  • M. Taraborelli
    • 1
  • I. Cavazzana
    • 1
  • N. Carabellese
    • 1
  • R. Ottaviani
    • 1
  • F. Allegri
    • 1
  • F. Franceschini
    • 1
  • N. Agmon-Levin
    • 2
  • Y. Shoenfeld
    • 2
    • 3
  • Angela Tincani
    • 1
  1. 1.Department of Clinical and Experimental SciencesUniversity of Brescia, Rheumatology and Clinical Immunology, A.O. Spedali CiviliBresciaItaly
  2. 2.Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  3. 3.Incumbent of the Laura Schwarz-Kip Chair for Research of Autoimmune Diseases, Sackler Faculty of MedicineTel-Aviv UniversityTel AvivIsrael

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