Background/Purpose: Obesity and abdominal adiposity have been frequently associated with inflammation. However, an association of obesity with a decreased likelihood of anti-nuclear antibodies (ANAs) was recently reported in the general population. We used data from adult participants ≥20 years of age in the National Health and Nutrition and Examination Survey 1999-2004 to further explore this association.

Methods: To rule out a possible previous history of autoimmune disease, participants were excluded if they reported a history of arthritis other than osteoarthritis, thyroid or liver disease, or steroid use. ANAs were screened using indirect immunofluorescence (IF). Titers were done on samples with IF≥ 3+. We subsequently strictly defined positive ANA as an ANA titer ≥ 1:160. Overweight and obesity were classified by traditional BMI criteria. High and low C-reactive protein (CRP) were defined using the 75^th 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 and were adjusted for demographics, comorbidities, smoking status, and total cholesterol. 

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). To study the effect of systemic inflammation, as measured by CRP, we then stratified our models based on the CRP cutpoint.  Among participants with low CRP (<0.42), 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 among those with high CRP (≥0.42) (OR 1.77, 95%CI 0.81-3.88).  When looking specifically 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. While 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. Therefore it is possible that body composition, particularly fat distribution, is driving autoimmunity in the general population even in the absence of systemic inflammation. Further studies are needed to determine if in fact this is the case.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-inverse-association-between-obesity-and-anti-nuclear-antibodies-is-modified-by-systemic-inflammation-and-maybe-associated-with-body-composition/