Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Patients with Systemic Autoimmune Rheumatic Disease (SARD) often have a prolonged pre-clinical phase during which they are anti-nuclear antibody (ANA) positive but lack clinical symptoms. It has been proposed that progression from asymptomatic autoimmunity to clinical disease is accompanied by immunologic changes that could be used as predictors of disease development. Our objective was to identify cyto/chemokine abnormalities in ANA+individuals who lack sufficient criteria for a diagnosis of SARD.
Methods: ANA+ individuals who: 1) lacked clinical symptoms of SARD (ANA No Symptoms, ANS); 2) had a least one clinical symptom of SARD (Undifferentiated Connective Tissue Disease, UCTD); or 3) had a recently diagnosed steroid and immunosuppressive naïve SARD were recruited, and compared with ANA– healthy controls (HC). The levels of 30 cyto/chemokines were measured, 29 by Luminex and one (BAFF) by ELISA. Peripheral blood interferon (IFN)-induced and BAFF gene expression was quantified by NanoString. The normalized levels of 5 ubiquitously expressed IFN-induced genes were summed to produce an IFN5 score.
Results: Cyto/chemokines were measured in plasma samples for 145 individuals (21 HC, 37 ANS, 28 UCTD, and 59 early SARD (6 SLE, 25 SjD, 25 SSc, and 3 MCTD/DM)). The plasma levels of four cyto/chemokines, IP-10, eotaxin, BAFF, and TNF-α, were significantly elevated in early SARD patients when compared to HC (Bonferroni corrected p = 0.0001, 0.0006, 0.003, 0.033, respectively). The levels of IP-10, eotaxin, and TNF-α were not significantly elevated in ANS and UCTD individuals as compared to HC. Although there was a trend to elevated serum BAFF levels in UCTD and ANS individuals, this only achieved statistical significance in UCTD patients (p = 0.037 and 0.065, respectively). However, ANS individuals had significant elevations of BAFF RNA in their peripheral blood (p = 0.009). We have previously reported that all ANA+ subgroups (ANS, UCTD and early SARD) have significantly elevated IFN5 scores. The levels of IP-10, serum BAFF, and BAFF RNA were positively correlated with IFN5 scores in ANA+individuals, suggesting that these pro-inflammatory factors are induced by type I IFN.
Conclusion: Although elevated levels of several pro-inflammatory factors are seen in early SARD patients, these factors are not elevated in ANA+ individuals who lack sufficient criteria for a diagnosis of SARD. Thus, elevations of pro-inflammatory factors appear to parallel progression to clinical disease.
To cite this abstract in AMA style:Hafiz W, Chang NH, Noamani B, Bonilla D, Lisnevskaia L, Silverman E, Bookman A, Johnson SR, Landolt-Marticorena C, Wither J. Lack of Pro-Inflammatory Cyto/Chemokines in ANA+ Individuals with Insufficient Criteria for a Diagnosis of Systemic Autoimmune Rheumatic Disease [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/lack-of-pro-inflammatory-cytochemokines-in-ana-individuals-with-insufficient-criteria-for-a-diagnosis-of-systemic-autoimmune-rheumatic-disease/. Accessed August 5, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/lack-of-pro-inflammatory-cytochemokines-in-ana-individuals-with-insufficient-criteria-for-a-diagnosis-of-systemic-autoimmune-rheumatic-disease/