PMC:3845430 / 4926-6066 JSONTXT

{"project":"2_test","denotations":[{"id":"24324289-9079816-25763397","span":{"begin":91,"end":93},"obj":"9079816"},{"id":"24324289-22829412-25763397","span":{"begin":91,"end":93},"obj":"22829412"},{"id":"24324289-12375308-25763398","span":{"begin":430,"end":432},"obj":"12375308"},{"id":"24324289-8343181-25763398","span":{"begin":430,"end":432},"obj":"8343181"},{"id":"24324289-12634237-25763398","span":{"begin":430,"end":432},"obj":"12634237"},{"id":"24324289-9079816-25763399","span":{"begin":692,"end":694},"obj":"9079816"},{"id":"24324289-214511-25763400","span":{"begin":855,"end":857},"obj":"214511"},{"id":"24324289-307690-25763401","span":{"begin":859,"end":861},"obj":"307690"},{"id":"24324289-8428220-25763402","span":{"begin":1130,"end":1132},"obj":"8428220"}],"text":"4. RFs in Healthy Subjects\nRF positivity has also been reported in the healthy population [31–33], and up to 4% of young Caucasians may be RF positive, with a similar distribution between the two genders. It is thought that genetic and environmental factors are responsible for the worldwide variability in distribution of RFs: for example, their highest prevalence (up to 30%) has been observed in North American Indians tribes [34–36]. The RFs found in healthy subjects are different from those present in RA patients as their titres are low/moderate and they are likely to be produced by CD5-expressing B cells as low-affinity, poly-reactive IgMs without any signs of maturation affinity [31]. The transient production of low-affinity IgM RFs may be induced by polyclonal B cell activators such as bacterial lipopolysaccharides and Epstein-Barr virus [28, 37], but it has been shown that high RF titres in healthy subjects predict the development of RA [38]. Furthermore, IgM RFs are sometimes observed in healthy elderly people, which suggests that they may be a consequence of the age-related immune deregulation (Figure 1) [39, 40].\n\n"}