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AB0289 Can cd11c expression successfully predict response to etanercept in rheumatoid arthritis patients?
  1. S. L. Smith1,
  2. D. Plant2,
  3. S. Eyre1,
  4. A. Yarwood1,
  5. K. L. Hyrich3,
  6. A. W. Morgan4,
  7. A. G. Wilson5,
  8. J. D. Isaacs6,
  9. A. Barton1,2,
  10. Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate
  1. 1Arthritis Research UK Epidemiology Unit, University of Manchester
  2. 2NIHR Manchester Musculoskeletal BRU, Manchester Academic Health Science Centre
  3. 3University of Manchester, Manchester
  4. 4University of Leeds, Leeds
  5. 5University of Sheffield, Sheffield
  6. 6Newcastle University, Newcastle, United Kingdom

Abstract

Background The treatment of rheumatoid arthritis (RA) with biologic drugs such as anti-tumor necrosis factor alpha (TNF) has significantly improved the clinical outcome in patients; however, 30-40% of patients fail to experience a satisfactory response. In an ideal scenario, an effective drug which is unlikely to induce serious adverse events would be selected for each patient prior to treatment, based on an algorithm including a variety of predictive markers which would include demographic data. CD11c (ITGAX) is an integrin molecule involved in the chemotaxis of immune cells and cell adhesion. Expression of CD11c in monocytes has been correlated with treatment response in RA patients receiving adalimumab monotherapy with a sensitivity of 100% and specificity of 91.7%. Whether this observation solely applies to adalimumab or whether this observation encompasses other anti-TNF drugs has yet to be investigated.

Objectives To assess pre-treatment levels of CD11c expression in RNA to determine whether expression levels can differentiate future responder and non-responder patients as assessed by the 28-joint disease activity (DAS28) score in etanercept treated patients with RA.

Methods Total RNA was extracted from pre-treatment whole blood samples of fifty patients (25 responders and 25 non-responders; defined using EULAR criteria at 3-month follow-up) from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS) longitudinal cohort. RNA was subsequently converted to high quality single stranded cDNA for use in gene expression profiling using the QuantStudio™ 12K Flex real-time qPCR system in order to measure CD11c, GAPDH and ACTB mRNA transcripts. The comparative CT method was then used to relatively quantify CD11c against the geometric average of the two housekeeping genes GAPDH and ACTB.

Results Etanercept responder and non-responder patients showed similar baseline CD11c expression levels when normalised against a geometric average of the two housekeeping genes. Slightly higher levels of expression were seen in the pre-treatment samples taken from future responders yielding a fold-change of 0.493 as compared to non-responders (p-value = 0.81).

Conclusions CD11c expression was not correlated with treatment outcome in etanercept treated RA patients. However, it cannot be excluded as a potential biomarker as this marker may only be specific to adalimumab and not other classes of anti-TNFs. Another possibility is that CD11c expression may be wholly cell-type specific resulting in masked signals which would be missed in whole blood RNA samples. Further experiments with specific cell populations and different biologics will be needed to confirm this hypothesis.

Disclosure of Interest None Declared

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