Background/Purpose:

Diagnosis of the preclinical phase of rheumatoid arthritis (pre-RA) allows timely start of treatment with the potential to prevent disease progression. It is known that antibodies against citrullinated proteins (ACPA) and rheumatoid factor (RF) have diagnostic value to identify pre-RA. However, since only 20-40% of ACPA+/RF+ arthralgia patients develop arthritis within 5 years, better prognostic markers are needed. Recently wedemonstrated involvement of  interferon (IFN) response and B-cell gene signaturespre-RA. The objective of this study is to demonstrate the value of these signatures in the diagnosis of pre-RA. 

Methods:

Peripheral blood (Paxgene) was collected from 115 ACPA⁺/RF⁺ arthralgia patients from Jan van Breemen Research Institute | Reade Amsterdam. Patients where clinically followed for arthritis development with a mean follow-up time of 23 months (IQR 12-30). During this period 44 arthralgia patients developed arthritis within a median time of 8 months (IQR 5-13). IFN response and B-cell related gene expression was measured by multiplex  qPCRs. An IFN score was calculated based on 7 highly correlating Type I IFN response genes.  A B-cell score was calculated based on three highly correlating B-cell related genes. Cut-off levels  for the IFN and B cell high or low definition was determined by the 95% CI of the levels in healthy controls. Cox regression analysis and Receiver Operating Characteristic curve analysis was used to demonstrate prognostic and diagnostic significance.

Results:

Cox regression analysis revealed that an IFN^high score was associated with arthritis development independent of ACPA status (RR 2.19, CI 1.007-4.739, P= 0.048). Inclusion of the B-cell score demonstrated that an IFN^low score combined with a B-cell^high score was associated with arthritis free survival (RR 0.375). To demonstrate the clinical utility of the IFN and B-cell signatures to separate pre-RA patients from arthritis free survival individuals we constructed an ROC-curve. The area under the curve (AUC) reached  0.802 (P=0.000), which is considered “good”. Based on these data a cut-off could be chosen for the diagnosis of pre-RA with a specificity of 85% and a sensitivity of 52%.

Conclusion:

These findings demonstrate the value of IFN and B cell gene signatures as biomarkers for the diagnosis of pre-RA.

This research was supported by the Center for Translational Molecular Medicine (CTMM) consortium “TRACER”.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/interferon-and-b-cell-gene-signatures-contribute-to-diagnosis-of-pre-clinical-rheumatoid-arthritis/