2016
DOI: 10.1002/art.39706
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Autoantibody‐Positive Healthy Individuals Display Unique Immune Profiles That May Regulate Autoimmunity

Abstract: Objective Antinuclear antibodies (ANA) are detected in approximately 18% of females, yet only 5–8% develop autoimmune disease. Immunological differences between ANA-positive (ANA+) healthy individuals and SLE patients may elucidate the regulatory mechanisms by which ANA+ individuals avoid transition to clinical autoimmune disease. Methods Healthy individuals (n=790) were screened for autoantibodies specific for 11 lupus, systemic sclerosis and Sjögren antigens. From this screen, 31 European-American ANA+ hea… Show more

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Cited by 87 publications
(86 citation statements)
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“…The overall median (interquartile range) serum level of IL-6 and CRP was 1.6 pg/mL (1.1, 2.7, reference range 0–5) and 1.3 mg/L (0.6, 4.5, reference range 0–10), respectively. The observed values of IL-6 and CRP in this cohort are comparable to those observed in other SLE cohorts (11, 12). The mean ± SD peak torques of knee extension and flexion were 44.2 ± 16.0 and 29.8 ± 11.5 N-m, respectively; and of grip strength was 22.4 ± 6.8 kg.…”
Section: Resultssupporting
confidence: 88%
“…The overall median (interquartile range) serum level of IL-6 and CRP was 1.6 pg/mL (1.1, 2.7, reference range 0–5) and 1.3 mg/L (0.6, 4.5, reference range 0–10), respectively. The observed values of IL-6 and CRP in this cohort are comparable to those observed in other SLE cohorts (11, 12). The mean ± SD peak torques of knee extension and flexion were 44.2 ± 16.0 and 29.8 ± 11.5 N-m, respectively; and of grip strength was 22.4 ± 6.8 kg.…”
Section: Resultssupporting
confidence: 88%
“…Although it is possible for up to 14% of the general population [8] without clinical signs or symptoms of SLE to have other facets of immune dysregulation, we have recently demonstrated that autoantibody-positive healthy individuals do not usually display enhanced dysregulation of those mediators compared to SLE patients, including IL-5, IL-6, and IFN-γ ( Table 4 ), that are dysregulated in patients at the highest risk of developing SLE [50, 51]. In addition, it is possible that immune pathways found to be dysregulated in asymptomatic individuals who develop SLE may also be present in other rheumatologic autoimmune diseases [52], to date, evaluation of serological samples from the DODSR and other community cohorts in asymptomatic patients who develop other diseases such as rheumatoid arthritis have revealed a combination of dysregulated immune pathways and autoantibody specificities distinct from that of preclinical SLE [53-55].…”
Section: Discussionmentioning
confidence: 99%
“…Mechanistically, our data suggests that the BANK1 risk protein acts through an inhibition of function resulting in a decrease in BCR/CD40L signaling, enhanced FOXO1 expression and subsequent memory B cell expansion as depicted in Figure 5. A recent study has shown that 7% of healthy control individuals are ANA + and that these subjects demonstrate an expansion of memory B cells, indicating that this is an early event in B cell dysregulation [48]. As B cells start to accumulate in at-risk subjects, other genetic and environmental factors could act as additional triggers resulting in a shift towards BCR hyper-responsiveness, due in part to loss of negative regulation of BCR signaling via decreased FCγRIIB and Lyn expression [49, 50].…”
Section: Discussionmentioning
confidence: 99%