Background/Purpose Antinuclear antibodies (ANAs) are present in a significant proportion of patients with rheumatoid arthritis (RA).  Positivity for ANA in RA has been associated with use of TNF inhibitor therapies and with the presence of overlapping disorders such as Sjogren’s syndrome.  We hypothesized that ANA positivity might be associated with other clinical or immunologic manifestations of RA.  

Methods Peripheral blood samples were obtained from CCP-positive RA patients (N=50) and 8 patients with systemic lupus erythematosus (SLE) who were seen in outpatient clinics.  Clinical and laboratory features of disease were determined by chart review.  Serum was used for measurement of ANA by ELISA and for detection of IgG and IgM autoantibodies on an 84-component protein array.  Whole blood samples were used for quantitation of expression levels of 3 genes in the Type I interferon signature (MX1, OAS1, IFI27) using real-time PCR.   Groups were compared for significant differences using 2-tailed t and Fisher’s exact tests.   Continuous variables were analyzed for correlations with Pearson’s test. 

Results

ANA positivity was present in 23/50 (46%) of the RA patients and this group tended to be older (60 vs 52 years; P=0.02), have longer mean disease duration (10 vs 7 years; P = 0.09), a lower prevalence of smoking (30% vs 63%; P=0.027), and somewhat higher prevalence of TNF inhibitor therapies (48% vs 26%; p=0.14) than the ANA negative group.   Gender distributions were similar.  The erythrocyte sedimentation rate was modestly correlated with ANA level (R=0.3; P=0.038).   Malignancies were exclusively seen in the ANA+ group (8 cancers in 6 patients; P=0.008 vs ANA-).   Only 2 of these were after starting TNF inhibitor therapy.  9 patients had lung disease, including interstitial fibrosis and bronchiectasis, and 6 of these were in the ANA+ group (NS), but lung disease in nonsmokers was only observed in ANA+ patients (P=0.038).    Two of the 27 ANA-negative patients had had a single joint replacement each, compared to 6/23 ANA-positive patients, 4 of whom had more than one replaced joint (P=0.027).   Other connective tissue diagnoses including Sjogren’s Syndrome and thyroid conditions were not different in the two groups.  On the autoantigen array, ANA + and – subgroups of RA did not show any significant differences for IgM autoantibodies while 12 IgG autoantibodies were higher in the ANA+ group (P £ 0.04).  Compared to SLE, the ANA+ RA group had significant elevation of 13 IgM autoantibodies, but did not show any elevated IgGs.  ANA positivity in the RA patients was not associated with elevation of the Type I IFN genes.  

Conclusion

ANA positivity in patients with CCP+ RA may define a clinical subset that has a greater risk of lung disease, malignancy and joint replacement surgery.  The presence of ANA was associated with elevation of the Type I IFN signature.   The paradoxical observation that smoking was less prevalent in the ANA+ group that had higher malignancy rates is not explained.  If ANA expression in RA is not associated with the Type I IFN signature as in SLE, then other pathogenetic pathways may be involved, possibly including those involved in immune surveillance.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-antinuclear-antibodies-with-lung-disease-malignancy-and-joint-replacement-in-rheumatoid-arthritis/