Presented at the 13th International Congress on Autoimmunity in Athens, Greece

Speaker: Juan-Manuel Anaya

Key Takeaways:

An Autoimmune Tautology refers to the fact that autoimmune diseases share several clinical signs and symptoms, physiopathological mechanisms, and genetic factors that support their having a common ancestor

Anaya has proposed several arguments that support the hypothesis and has updated them to include:

Female predominance

Shared sub phenotypes

Polyautoimmunity

Coaggregation (familial autoimmunity)

Age at onset and severity

Similar pathophysiology

Similar environmental factors (autoimmune ecology)

Similar genetic factors

Ancestry

Treatment

Summary:

Anaya originally stated that “although autoimmune diseases exhibit contrasting epidemiological features, pathology, and clinical manifestations, three lines of evidence demonstrate that these diseases share similar immunogenetic mechanisms (that is, autoimmune tautology). First, clinical evidence highlights the co-occurrence of distinct autoimmune diseases within an individual (that is, polyautoimmunity) and within members of a nuclear family (that is, familial autoimmunity). Second, physiopathologic evidence indicates that the pathologic mechanisms may be similar among autoimmune diseases. Lastly, genetic evidence shows that autoimmune phenotypes might represent pleiotropic outcomes of the interaction of non-specific disease genes.”

Further explanations regarding the updated tautology hypothesis:

1. Female predominance

  • “Almost 5% of the world population develops an AD. Of this 5%, approximately 80% are women”.
  • Women tend to have a different age at onset and different disease activity than men – the more frequent the autoimmune disease and the later it appears, the more women are affected.
  • The most convincing explanation of female-biased autoimmunity remains the hormonal theory followed by genetic factors

 

2. Shared sub-phenotypes among autoimmune diseases

  • Seen in clinical settings and in the laboratory (presence of antinuclear antibodies, rheumatoid factor, anti-Ro antibodies)
  • Systemic autoimmune diseases have similar signs and symptoms.

 

3. Polyautoimmunity

  • Refers to the fact that autoimmune diseases may co-occur within a patient
  • Latent polyautoimmunity refers to the presence of autoantibodies or biomarkers of autoimmunity unrelated to an undergoing autoimmune disease (non specific), with no clinical symptoms or signs of such an additional autoimmune condition. Overt polyautoimmunity is the presence of two or more well-characterized and clinically manifested autoimmune diseases in a single patient. This is called Multiple autoimmune syndrome if three or more are present.
  • How common is overt polyautoimmunity? Frequent – Systemic Lupus Erythematosus 14-41%, Rheumatoid Arthritis 14%, Sjogren’s 33-52%, Systemic sclerosis 38%, Celiac Disease 33%, Myasthenia Gravis 13%
  • No consensus in literature regarding severity, some say there is less severity with polyautoimmunity and some say more severity

 

4. Aggregation (Familial autoimmunity)

  • Familial autoimmunity (diverse autoimmune diseases on multiple members of a nuclear family) seems to be more frequent than familial autoimmune disease (that is, one specific autoimmune disease in various members of a nuclear family)
  • When familial autoimmunity is present the risk is the same for men and women, but when not present its higher in women

 

5. Age at onset and severity

  • Autoimmune diseases tend to be more severe in younger patients
  • Early-onset traits are more sensitive to genetic influence, while late-onset traits are more affected by environmental influences

 

6. Similar pathophysiology

  • Common mechanisms
  • Phenotype varies depending on the target organ
  • Imbalance of regulatory cells
  • Type 1 interferon is a central factor in autoimmunity
  • Th17 cells in inflammation and autoimmunity

 

7. Similar environmental factors (autoimmune ecology)

 

8. Similar genetic factors

 

9. Ancestry

  • Amerindian ancestry influences the risk of acquiring ADs as well as its severity (1) (2) (3)

 

10. Treatment

  • The same pharmacological agent (biologic and non-biologic) may be useful in treating diverse autoimmune diseases.
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