Smell and autoimmunity: A comprehensive review

Carlo Perricone, Netta Shoenfeld, Nancy Agmon-Levin, Caterina De Carolis, Roberto Perricone, Yehuda Shoenfeld*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


The sense of smell is an ancient sensory modality vital for sampling and perceiving the chemical composition of surrounding environments. Olfaction involves a pathway of biochemical and electrophysiological processes, which allows the conversion of molecular information into sensations. Disturbances in the olfactory function have been investigated mainly in neurological/ neurodegenerative disorders such as Alzheimer's and Parkinson's diseases; impaired sense of smell has been associated with depressed mood. Only recently, smell capability was tested in other diseases, particularly autoimmune diseases. Shoenfeld and colleagues opened this chapter showing that patients affected with systemic lupus erythematosus (SLE) have disturbances in their olfactory functions and revealed its association with neuropsychiatric manifestations of the disease. This evidence was confirmed in experimental models and replicated in other SLE populations. The connection between autoimmunity and the sense of smell was lately emphasized by studies on patients with Sjögren's syndrome and in patients with other autoimmune/immune-mediated diseases, such as polydermatomyositis, recurrent spontaneous abortion, and hereditary angioedema. Genetic susceptibility and hormonal and environmental factors may play a role in these conditions. Olfactory receptor gene clusters are located in proximity to key locus of susceptibility for autoimmune diseases such as the major histocompatibility complex, suggesting not only a physic linkage, but a functional association. Nonetheless, gender- and hormone-mediated effects are fundamental in the development of autoimmune diseases. The different connections between smell and autoimmunity, genes and hormones may suggest that this is another tessera of a mosaic which is waiting the answer of Oedipus.

Original languageEnglish
Pages (from-to)87-96
Number of pages10
JournalClinical Reviews in Allergy and Immunology
Issue number1
StatePublished - Aug 2013


  • Antiphospholipid syndrome
  • Autoimmunity
  • Pregnancy
  • Smell
  • Systemic lupus erythematosus


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