An autoantibody profile identified by human genome‐wide protein arrays in rheumatoid arthritis

TL;DR

Researchers identified a set of autoantibodies that could help diagnose rheumatoid arthritis, especially in patients who do not have ACPA antibodies.

Contribution

The study introduces a new set of autoantibodies that may serve as diagnostic markers for ACPA-negative rheumatoid arthritis.

Findings

Five autoantibodies were found to be elevated in ACPA-negative rheumatoid arthritis patients.

Anti-parathymosin showed the highest prevalence in early-stage ACPA-negative rheumatoid arthritis.

A prediction model using 44 autoantibodies achieved 90.8% specificity and 66.1% sensitivity in diagnosing rheumatoid arthritis.

Abstract

Precise diagnostic biomarkers of anticitrullination protein antibody (ACPA)‐negative and early‐stage RA are still to be improved. We aimed to screen autoantibodies in ACPA‐negative patients and evaluated their diagnostic performance. The human genome‐wide protein arrays (HuProt arrays) were used to define specific autoantibodies from the sera of 182 RA patients and 261 disease and healthy controls. Statistical analysis was performed with SPSS 17.0. In Phase I study, 51 out of 19,275 recombinant proteins covering the whole human genome were selected. In Phase II validation study, anti‐ANAPC15 (anaphase promoting complex subunit 15) exhibited 41.8% sensitivity and 91.5% specificity among total RA patients. There were five autoantibodies increased in ACPA‐negative RA, including anti‐ANAPC15, anti‐LSP1, anti‐APBB1, anti‐parathymosin, and anti‐UBL7. Anti‐parathymosin showed the highest prevalence of 46.2% (p = 0.016) in ACPA‐negative early stage (<2 years) RA. To further improve the diagnostic efficacy, a prediction model was constructed with 44 autoantibodies. With increased threshold for RA calling, the specificity of the model is 90.8%, while the sensitivity is 66.1% (87.8% in ACPA‐positive RA and 23.8% in ACPA‐negative RA) in independent testing patients. Therefore, HuProt arrays identified RA‐associated autoantibodies that might become possible diagnostic markers, especially in early stage ACPA‐negative RA.

HuProt array is a genome‐wide protein array suitable for high throughput unbiased analysis of autoantibodies against the entire human proteome without protein modifications.

We performed RA autoantibody screening in 182 RA patients and 261 controls with HuProt arrays to identify the nonmodified protein antibody profile of RA, especially in ACPA negative patients.

There were five autoantibodies increased in ACPA‐negative RA (anti‐ANAPC15, anti‐LSP1, anti‐APBB1, anti‐parathymosin, and anti‐UBL7). Among them, anti‐parathymosin showed the highest prevalence of 46.2% (p = 0.016) in ACPA‐negative and early stage (<2years) RA. Prediction model with 44 markers was also constructed with specificity of 90.8%, while the sensitivity is 66.1% (87.8% in ACPA‐positive RA patients and 23.8% in ACPA‐negative RA).

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