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OP0078 Presence of an Interferon Signature in Anti-Nuclear Antibody Positive Individuals Prior to the Onset of Systemic Autoimmune Rheumatic Disease
  1. J. Wither1,
  2. T. Liu1,
  3. B. Noamani1,
  4. D. Bonilla1,
  5. S. Johnson1,2,
  6. L. Lisnevskaia3,
  7. E. Silverman4,
  8. A. Bookman1,
  9. C. Landolt-Marticorena1
  1. 1University Health Network
  2. 2Mount Sinai Hospital, Toronto
  3. 3Lakeridge Health Center, Oshawa
  4. 4Hospital for Sick Children, Toronto, Canada


Background Patients with systemic autoimmune rheumatic diseases (SARD) often have a prolonged pre-clinical phase during which they are anti-nuclear antibody (ANA)+ 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. Elevated levels of interferon (IFN)-induced gene expression, termed the IFN signature, are found in several SARD conditions, and IFNs appear to play an important role in disease pathogenesis.

Objectives To determine whether ANA+ individuals who lack sufficient symptoms for a SARD diagnosis share the IFN-signature.

Methods ANA+ individuals who: 1) lacked clinical symptoms of SARD (ANS); 2) had a least one clinical symptom of SARD (Undifferentiated Connective Tissue Disease, UCTD); or 3) had a recently diagnosed SARD (Systemic Lupus Erythematosus, SLE; Sjogren's Disease, SjD; Scleroderma, SSc; Mixed Connective Tissue Disease, MCTD; Dermatomyositis, DM) were recruited from clinics at UHN/MSH hospitals. None of the patients were on corticosteroids or DMARDs with the exception of hydroxychloroquine. Healthy controls (HC) were also recruited. RNA was prepared from blood archived in Tempus tubes. Expression of 5 IFN-induced genes was quantified by Nanostring, normalized to expression of housekeeping genes, and summed to generate an IFN5 score. ANAs and levels of specific autoantibodies were measured by the hospital laboratory.

Results To date we have measured the IFN signature on 95 individuals (21 HC, 21 ANS, 16 UCTD, 22 SjD, 7 SSc, 6 SLE, 1 MCTD, 1 DM). There was a trend to higher mean IFN score in all groups as compared to HC (mean ± SD: HC 7,071±6,321; ANS 27,245±36,037; UCTD 27,624±24,827; SSc 34,940±40,940; SjD 61,877±33,404; SLE 62,769±50,233; MCTD/DM 97,716±24,973), which achieved statistical significance for ANS, UCTD, SjD, and SLE (corrected p=0.044, 0.003, <0.0001, 0.0075, respectively). Using a cutoff of 2 SD above the mean of HC as indicative of an elevated IFN5 score; 8/21 ANS, 8/16 UCTD, 3/7 SSc, 18/22 SjD, 5/6 SLE, and 2/2 MCTD/DM participants had elevated IFN levels. Marked elevations of the IFN5 score were seen in a subset of ANS and UCTD participants, which could not be attributed to recent infection. Although there was a significant correlation between the ANA titer (p=0.002) and IFN5 score for all ANA+ individuals, this was not seen in the ANS or UCTD subsets of this population. However the IFN5 score was positively correlated with the number of different ANA specificities present in the UCTD subset (p=0.048) and all ANA+ individuals (p<0.0001). Within the ANS subset, there was a strong correlation between the presence of anti-Ro/La antibodies with 6/8 IFN5 high as compared to 1/13 IFN low individuals being antibody positive (p=0.003).

Conclusions An IFN signature is seen in a subset of ANA+ individuals prior to a confirmed diagnosis of SARD and appears to correlate with the type and number of specific ANAs rather than onset of clinical disease.

Disclosure of Interest None declared

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