Background/Purpose: The Autoimmune/Inflammatory Syndrome
induced by adjuvants (ASIA) [1] 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 control-case study is to investigate prior exposures to adjuvant in
84 patients affected with UCTD and 84 age and sex-matched controls with no
family history of autoimmunity.

Methods: An ad hoc created questionnaire that lists
exposure to the possible triggers of “ASIA”, such as vaccinations (HBV vaccine,
HAV vaccine, tetanus toxoid vaccine, Haemophilus Influenzae vaccine,
Measles-Mumps-Rubella vaccine, Pneumococcal vaccine, HPV vaccine) foreign
materials (earrings, piercing, tattoos, silicon breast implants, skin fillers,
tooth amalgam, contact lenses, intrauterine device, cardiac valves, artificial
joints, metal implants), environmental and occupational exposures (living
and/or working near metal or chemical factories, landfills, airports or
highways) was administered to both cases and controls. For both groups autoantibodies
were analyzed (i.e. antinuclear, anti-ENA, anti-dsDNA, anti-cardiolipin, anti-β2glycoprotein I). Continuous variables were reported as mean and standard deviation, while percentages were reported
for categorical variables. T-test was calculated for continuous variables while
Chi-square or Fisher’s exact tests was used for categorical variables. All
statistical tests were two-tailed and only a p value < 0.05 was considered
statistically significant.

Results: The Table reports demographic information of the
enrolled subjects and those items that were significantly different between
cases and controls. As "molecular mimicry" between β2glycoprotein
I and tetanus toxoid was described [2], we indeed found that there is a trend
toward a higher prevalence of anti-β2glicoprotein I in UCTD who had
received a tetanus vaccine in the 10 years before the diagnosis (17/66, 25,7%) in
comparison with UCTD patients who did not receive it (3/27, 11,1%) (p=0,10).

Conclusion: As compared with healthy subjects, UCTD patients
appeared to have had a greater exposure to adjuvants: HBV and tetanus toxoid
vaccinations, metal implants and cigarette smoking. The increased prevalence of
allergies proved that UCTD patients have a more reactive immune system, likely
on a genetic basis. Thus we can suggest that ASIA and UCTD are two 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.

[1]  Shoenfeld
Y, Agmon-Levin N. J Autoimm 2011;36:4-8.

[2] Stojanović M et al.
Immunol Res.
2013;56:20-31.