Statistics from Altmetric.com
The reasons underlying the appearance of autoantibodies are poorly understood. The recent proposal that childhood infections prevent both autoantibody formation and occurrence of autoimmune diseases1,2 led to the suggestion that widespread vaccination against infectious diseases might favour the development of autoimmune diseases.2
To verify whether repeated infections from childhood prevent autoantibody formation we compared the prevalence of antinuclear antibodies (ANA), autoantibodies of infrequent occurrence in healthy controls from Western Europe and associated with systemic lupus erythematosus (SLE) and other autoimmune diseases, in populations with different prevalence of infections throughout the course of life—namely, African immigrants to Italy and Italians.
METHODS AND RESULTS
We obtained written informed consent from 137 Ghanaian or Nigerian apparently healthy immigrants to Italy and living in Verona (northeastern Italy), unrelated to patients with SLE or other autoimmune diseases, characterised by ANA positivity. We drew blood samples which were first tested for anti-HIV antibodies. Thirteen positive subjects were excluded from the survey. In the remaining 124 (mean age 35, range 8–53 years; 58 women) we looked for the presence of ANA by immunofluorescence on Hep-2 cells. We selected anti-HIV negative subjects to exclude the influence of anti-HIV antibody cross reactivity or HIV infection itself on the results of ANA determination; we also excluded relatives of patients with ANA positive autoimmune diseases because ANA positivity is more common in this subgroup.3,4
All the subjects studied recalled at least four episodes of malaria and three episodes of diarrhoea of at least 5 days’ duration. Hence the immigrant study population had been exposed to repeated infections during their lifetime. The prevalence (reciprocal titres 40–320) of ANA was found to be very high (27.4%, comparable to that of relatives of white patients with SLE)4 and even higher in more recent immigrants (table 1). Of the 34 positive subjects, 17 were women and 17 men; their mean (SD) age was 33 (8). As a control population, we used 375 white northeastern Italian subjects matched for age and sex and found an ANA prevalence of 3.5% (p<0.01).
Our data strongly suggest that living in an “infectious” environment from early life does not prevent, but rather favours, the formation of ANA. Although the reasons underlying their appearance are obscure, a role for a molecular mimicry between nuclear components of normal cells and parasitic or viral antigens cannot be excluded, as this has been demonstrated with the hepatitis B virus DNA polymerase.5
The finding that ANA positivity is far higher in recent immigrants is intriguing, as they are younger and therefore expected to have a lower incidence of autoantibodies than older subjects. Furthermore, although ANA are more frequently detected in women, we did not observe a preponderance in the female immigrant population tested. Although a definitive demonstration would require repeated testing of immigrants and demonstration of loss of ANA positivity over time, the present findings do suggest that the longer a person lives in a “less infectious” environment, the higher is the probability that they will be autoantibody negative.
Interestingly, none of the ANA positive subjects have developed any symptoms of autoimmune diseases in a mean follow up of 18 months.
In conclusion, our data demonstrate that markers of autoimmunity, such as ANA, are frequently found in Africa-born people but tend to be lost if they live for a long time in Western countries. Their presence should not therefore be regarded as predictive of SLE, a conclusion which confirms findings from studies in developed countries.6
Prospective epidemiological studies are needed both in developed and developing countries if the real mechanisms leading to overt autoimmune diseases are to be understood. Meanwhile, vaccination programmes in developing countries can continue without any concerns about a possible increase in the incidence of autoimmune diseases.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.