The Association between Anti-Nuclear Antibodies and Obesity is Likely Mediated by Abdominal Adiposity and Systemic Inflammation

Abstract

Background: Obesity and abdominal adiposity have been associated with inflammation as have the presence of anti-nuclear antibodies (ANAs). It was recently reported that there is a decreased likelihood of ANAs in the obese general population. To examine this relationship we used data from adult participants in the National Health and Nutrition and Examination Survey 1999-2004. Methods: Participants were excluded if they reported a history of arthritis other than osteoarthritis, thyroid or liver disease, or steroid use so as to rule out a history of possible prior autoimmune disease. We strictly defined a positive ANA as a titer ≥ 1:160. Overweight and obesity were classified using traditional BMI criteria. High and low C-reactive protein (CRP) were defined using the 75th percentile cutpoint as ≥0.42 and <0.42 mg/dL, respectively. Dual-energy X-ray absorptiometry (DEXA) was used to determine body composition. Logistic regression models were created to examine associations with ANA status. Results: 2552 participants were included in our analyses. Obese participants were older (p<0.001), more likely to be men (p=0.004) and to have comorbidities, and had higher levels of CRP (<0.001). After multivariable adjustment, obesity was associated with a decreased odds of having ANAs (OR 0.78, 95%CI 0.62-0.99). However when adding log-transformed CRP into our model, this association was no longer significant (OR 0.85, 95%CI 0.62-1.15), and there was evidence of effect modification by CRP (p=0.12). Among participants with low CRP, obesity was again associated with a reduced likelihood of ANA positivity (OR 0.69, 95%CI 0.48-0.99), but a trend was seen in the opposite direction in those with high CRP (OR 1.77, 95%CI 0.81-3.88). When looking at the 1143 obese and overweight participants with low CRP, ANA positivity was associated with a higher prevalence of cardiovascular disease (p=0.02) and higher % total body fat (p=0.007), trunk fat (p=0.02), and non-trunk fat (p=0.004). This association, however, was not found in the high CRP group. Conclusion: In the general population the association of obesity with ANA is modified by the presence of systemic inflammation as measured by CRP, where the inverse association previously found is eliminated when controlling for CRP. This inverse relationship remains among obese participants with low CRP, when these obese and overweight participants are ANA positive; it is associated with greater total body and trunk fat. It is possible that body composition is driving autoimmunity in the general population even in the absence of systemic inflammation.